warfarin and Intracranial-Hemorrhages

Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.. Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.. Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.. The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.

Topics: Administration, Oral; Amiodarone; Anticoagulants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Cytochrome P-450 CYP3A Inhibitors; Embolism; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Warfarin

The relative effectiveness of anticoagulation agents in patients with atrial fibrillation (AF) who survive an intracranial hemorrhage (ICH) is unknown. This study was performed to examine the comparative effectiveness of different oral anticoagulation (OAC) on clinical outcomes in this group of patients.. We performed a Bayesian network meta-analysis of randomized controlled trials (RCTs) and observational studies comparing different OAC (direct oral anticoagulant [DOAC] and warfarin) for the treatment of patients with AF who sustained ICH. Outcomes included repeat ICH, thromboembolic events, and all-cause mortality. The values derived from the surface under the cumulative ranking curve were obtained to rank the treatment hierarchy.. We identified 12 studies (two RCTs and ten observational studies) involving 23,265 patients; 346 patients were treated with any OAC agents; 5,006 received DOAC; 5,271 received warfarin; 12,007 received antiplatelet or no therapy, and 635 did not received relevant therapy. Both DOAC and warfarin (RR, 0.58; 95% CI, 0.45-0.74; RR, 0.83; 95% CI, 0.69-0.98) were superior to antiplatelet or no therapy in preventing thromboembolic events. Moreover, DOAC also showed superiority in preventing thromboembolic events (RR, 0.70; 95% CI, 0.58-0.83), repeat ICH (RR, 0.52; 95% CI, 0.40-0.67), and all-cause mortality (RR, 0.51; 95% CI, 0.46-0.56) than warfarin.. Our study suggests DOACs may be a reasonable alternative to anti-platelet therapy and warfarin for patients with AF who experienced ICH. However, given the available evidence is primarily observational, further validation by ongoing trials directly comparing these two classes of drugs are needed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Thromboembolism; Warfarin

In patients with mechanical heart valve protheses, warfarin is usually recommended because of its exceptional anticoagulation effects. However, warfarin can cross the placenta, leading to teratogenicity and even catastrophic hemorrhage in the fetus. The present article describes a case of warfarin-associated fetal intracranial hemorrhage. The patient was a woman in her early 30s. At the age of 11 years, she had undergone aortic valve replacement (mechanical) for aortic regurgitation. Since then, she had been taking oral warfarin. During her pregnancy, her prothrombin time-international normalized ratio was maintained between 1.5 and 2.5. At 35 weeks of gestation, fetal ultrasonography revealed an intracranial mass in the left hemisphere. An emergency cesarean section was performed because fetal intracranial hemorrhage was suspected. A male infant was delivered with a 1- 5-, and 10-minute Apgar score of 1, 5, and 7, respectively. Cranial computed tomography revealed multiple hemorrhage sites with newly emerged bleeding spots. In patients with mechanical heart valve protheses, obstetricians face the dilemma of individual-patient differences and the difficulty of intensive monitoring of the coagulation parameters in the fetus. Tailor-made anticoagulation therapy and a more intensive ultrasonic monitoring strategy, even that involving regular magnetic resonance imaging, are necessary in these patients.

Topics: Anticoagulants; Cesarean Section; Child; Female; Fetus; Heart Valve Prosthesis; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Mothers; Pregnancy; Warfarin

Pivotal trials comparing direct oral anticoagulants (DOACs) against warfarin in patients with atrial fibrillation (AF) predominantly involved patients with high stroke risk. This study aimed to evaluate the efficacy and safety of DOAC versus warfarin in patients with low stroke risk. An online literature search was conducted to retrieve studies comparing clinical outcomes between patients treated with DOAC versus warfarin for AF, reporting outcomes for patients at low or minimal risk of stroke (CHA

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Intracranial Hemorrhages; Risk Factors; Stroke; Treatment Outcome; Warfarin

The meta-analysis of randomized controlled trials has illustrated that the efficacy of low-dose non-vitamin K antagonist oral anticoagulants is inferior compared with standard-dose non-vitamin K antagonist oral anticoagulants, though they are still frequently prescribed for Asian patients with non-valvular atrial fibrillation. We aimed to further investigate the efficacy and safety of low-dose non-vitamin K antagonist oral anticoagulants by carrying out a meta-analysis of all relevant randomized controlled tri- als and cohort studies.. Cochrane Central Register of Controlled Trials, Embase, and MEDLINE were sys- tematically searched from the inception to September 9, 2021, for randomized controlled trials or cohorts that compared the efficacy and/or safety of low-dose non-vitamin K antagonist oral anticoagulants in Asian patients with non-valvular atrial fibrillation. The primary outcomes were stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage, and gastrointestinal hemorrhage. Hazard ratios and 95% CIs were estimated using the random-effect model.. Nineteen publications involving 371 574 Asian patients with non-valvular atrial fibrillation were included. Compared with standard-dose non-vitamin K antagonist oral anticoagulants, low-dose non-vitamin K antagonist oral anticoagulants showed compa- rable risks of stroke (hazard ratio, 1.18; 95% CI 0.98 to 1.42), major bleeding (hazard ratio, 1.00; 95% CI 0.83 to 1.21), intracranial hemorrhage (hazard ratio, 1.13; 95% CI 0.92 to 1.38), and gastrointestinal hemorrhage (hazard ratio, 1.07; 95% CI 0.87 to 1.31), though had a higher risk of mortality (hazard ratio, 1.34; 95% CI 1.05 to 1.71). Compared with warfarin, low-dose non-vitamin K antagonist oral anticoagulants were associated with lower risks of stroke (hazard ratio, 0.73; 95% CI 0.67 to 0.79), mortality (hazard ratio, 0.69; 95% CI 0.60 to 0.81), major bleeding (hazard ratio, 0.62; 95% CI 0.51 to 0.75), intracranial hemor- rhage (hazard ratio, 0.48; 95% CI 0.33 to 0.69), and gastrointestinal hemorrhage (hazard ratio, 0.78; 95% CI 0.65 to 0.93).. Low-dose non-vitamin K antagonist oral anticoagulants were superior to warfarin, and comparable to standard-dose non-vitamin K antagonist oral anticoagu- lants considering risks of stroke, major bleeding, intracranial hemorrhage, and gastroin- testinal hemorrhage. Further, high qualified studies are warranted.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Treatment Outcome; Warfarin

For patients with atrial fibrillation who survive an intracranial hemorrhage (ICrH), the decision to offer oral anticoagulation (OAC) is challenging and necessitates balancing risk of thromboembolic events with risk of recurrent ICrH.. This systematic review assesses the effectiveness and safety of OAC and/or antiplatelets in patients with atrial fibrillation with nontraumatic ICrH. Bibliographic databases CENTRAL, MEDLINE, EMBASE, and CINAHL were searched. Articles on adults with atrial fibrillation with spontaneous ICrH (intracerebral, subdural, and subarachnoid), receiving antithrombotic therapy for stroke prevention were eligible for inclusion.. Twenty articles (50 470 participants) included 2 randomized controlled trials (n=304)' 8 observational studies, 8 cohort studies, and 2 studies that meta-analyzed individual-level data from observational studies. OAC therapy was associated with a significant reduction in thromboembolic events (summary relative risk [sRR], 0.51 [95% CI, 0.30-0.86], heterogeneity I. In nontraumatic ICrH survivors with atrial fibrillation, OAC therapy is associated with a reduced risk of thromboembolic events and all-cause mortality without significantly increasing risk of recurrent ICrH. This finding is primarily based on observational data, and further larger randomized controlled trials are needed to corroborate or refute these findings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Thromboembolism; Warfarin

Nonvalvular atrial fibrillation (NVAF) is the most common arrhythmia. It is of a high disability and death rate, and seriously affects quality of life. Although New oral anticoagulants (NOACs) are recommended for anticoagulation therapy of atrial fibrillation, they are not widely used for the high cost and limited availability. Warfarin is effective and economical. The risk of thromboembolism and anticoagulant hemorrhage is higher in patients >65 years with NVAF. So, it is of great clinical significance to explore the optimal anticoagulation intensity of warfarin in patients >65 years of China, and other ethnicities. Some studies suggested that low-intensity international normalized ratio (INR) has similar antithrombotic efficacy comparing to standard-intensity INR, whereas bleeding risk was significantly reduced. But others showed conflicting results. We pooled the efficacy and safety data of low- and standard-intensity warfarin therapy for patients over 65 years with NVAF by meta-analysis, as to evaluate optimal INR intensity of warfarin therapy in patients over 65 years. We identified 18 studies providing data of 2105 patients receiving anticoagulation therapy with warfarin. On meta-analysis (odds ratio [OR] [95% confidence interval {CI}]), low-intensity INR conferred similar efficacy to standard intensity INR on all thrombosis (1.28 [0.90 to 1.81]), stroke (1.09 [0.67 to 1.77]), other thromboembolism ([peripheral and pulmonary embolism] 2.26 [0.89 to 5.79]), and all cause death (1.38 [0.94 to 2.02]). Low-intensity INR conferred better safety profile than standard intensity INR in major bleeding (intracranial and gastrointestinal hemorrhage) (0.32 [0.19 to 0.52]), minor bleeding (gum, nasal cavity and conjunctival hemorrhage, skin ecchymosis, hematuria, hemoptysis) (0.30 [0.20 to 0.45]), and all bleeding (0.30 [0.22 to 0.40]). In conclusion, low-intensity INR (1.5 to 2.0) of warfarin therapy is as effective as standard intensity INR (2.0 to 3.0) therapy in reducing thromboembolic risk in patients>65 years with NVAF, and has a safer profile of bleeding.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Mortality; Patient Care Planning; Pulmonary Embolism; Stroke; Thromboembolism; Thrombosis; Warfarin

To assess the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation (AF) after the use of rivaroxaban or warfarin. To investigate the effects of rivaroxaban and warfarin on gastrointestinal and intracranial hemorrhage in patients with AF, we searched PubMed, Embase, and Medline from the establishment of databases up to 2020. We finally included 38 observational studies involving 1 312 609 patients for the assessment of intracranial hemorrhage, and 33 observational studies involving 1 332 956 patients for the assessment of gastrointestinal bleeding. The rates of intracranial hemorrhage were 0.55% in the rivaroxaban group versus 0.91% in the warfarin group (OR 0.59; 95% CI 0.53-0.66; p < .00001, I2 = 78%). The rates of gastrointestinal bleeding were 2.63% in patients with rivaroxaban versus 2.48% in those with warfarin (OR 1.06; 95% CI 0.96-1.17; p < .00001, I2 = 94%). Rivaroxaban could significantly reduce the risk of intracranial hemorrhage in patients with AF than warfarin, but the risk of gastrointestinal bleeding remained controversy due to no statistical significant difference. Notably, a subgroup analysis demonstrated that patients in rivaroxaban group with severe chronic renal diseases or undergoing hemodialysis exposed to less gastrointestinal hemorrhage risk than the group from warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Rivaroxaban; Stroke; Warfarin

This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in secondary stroke prevention in atrial fibrillation (AF) patients.. PubMed and Embase electronic databases were systematically searched from January 2009 to July 2019 for relevant randomized clinical trials and observational studies. A random-effects model was applied in the pooled analysis.. A total of 14 studies (4 randomized clinical trials and 10 observational studies) were included. Based on the randomized clinical trials, compared with VKA use, the use of NOACs was associated with decreased risk of stroke and systemic embolism, major bleeding, and intracranial bleeding. Based on the observational studies, compared with VKAs, the subgroup analysis showed that dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran and apixaban were associated with a decreased risk of major bleeding.. Based on current data, the use of NOACs is at least non-inferior to the use of VKAs in AF patients for secondary stroke prevention irrespective of NOAC type.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Observational Studies as Topic; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Secondary Prevention; Stroke; Thiazoles; Treatment Outcome; Vitamin K; Warfarin

Ischaemic stroke and systemic embolism are the major potentially preventable complications of atrial fibrillation (AF) leading to severe morbidity and mortality. Anticoagulation using vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOACs) is mandatory for stroke prevention in AF. Following approval of the four NOACs dabigatran, rivaroxaban, apixaban, and edoxaban, the use of VKA is declining steadily. Increasing age with thresholds of 65 and 75 years is a strong risk factor when determining annual stroke risk in AF patients. Current recommendations such as the "2016 Guidelines for the management of atrial fibrillation" of the European Society of Cardiology and the "2019 AHA/ACC/HRS Focused Update" by the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society strengthen the importance of anticoagulation and detection of bleeding risks, of which older age is an important one. While patients aged ≥ 75 years are usually underrepresented in randomised clinical trials, they represent almost 40% of the trial populations in the large NOAC approval studies. Therefore, a sufficient amount of data is available to assess the efficacy and safety for this patient cohort in that specific indication. In this article, the evidence for stroke prevention in AF using either VKA or NOACs is summarised with a special focus on efficacy compared to bleeding risk in patients aged ≥ 75 years. Specifically, we used a model of increased weighing of intracranial bleeding to illustrate the potential benefit of NOACs over VKA in the elderly population. In brief, there are at least two tested strategies with apixaban and edoxaban which even confer an additional clinical net benefit compared with VKA. Furthermore, elderly subgroups of trials for combined antithrombotic treatment following percutaneous coronary interventions in anticoagulated patients are analysed.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Vitamin K; Warfarin

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Intracranial Hemorrhages; Perioperative Care; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical factors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dose NOACs when given as pre-specified in pivotal trials.. Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69-1.03)] and on major bleeding [RR 0.70 (95% CI 0.50-0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77-0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70-1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each).. Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.

Topics: Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiazoles; Warfarin

Topics: Anticoagulants; Blood Coagulation Factors; Humans; Intracranial Hemorrhages; Warfarin

Data regarding the efficacy and safety of warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) among patients with chronic kidney disease (CKD) remain scarce.. Fifteen studies (7 comparing NOAC vs warfarin and 8 comparing warfarin vs no anticoagulant) were identified comprising 78,053 patients. Warfarin (vs no anticoagulant) was associated with reduced risk of ischemic stroke (risk ratio [RR] = 0.68; 95% confidence interval [CI] 0.55-0.84]) and mortality (RR = 0.70; 95% CI 0.62-0.78). In comparison to warfarin, NOAC use lowered the risk of ICH (RR = 0.43; 95% CI 0.33-0.56), stroke. Among patients with CKD treated with oral anticoagulants, NOACs present with a more favorable safety and efficacy profile for various cardiovascular outcomes.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Intracranial Hemorrhages; Mortality; Renal Insufficiency, Chronic; Stroke; Warfarin

Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation.. We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs.. From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (. Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Female; Humans; Intracranial Hemorrhages; Male; Polymers; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Saliva, Artificial; Stroke; Vitamin K; Warfarin

The standardization for the clinical use of drug therapy for cerebral infarction (CI) has not yet determined in some aspects. In this paper, we discussed the efficacies of different drug therapies (aspirin, aspirin plus dipyridamole, aspirin plus clopidogrel, aspirin plus warfarin, cilostazol, warfarin, and ticlopidine) for CI.. We searched databases of PubMed and Cochrane Library from the inception to April, 2017, randomized controlled trials (RCTs) met the inclusion and exclusion criteria were enrolled in this study. The network meta-analysis integrated evidences of direct and indirect comparisons to assess odd ratios (OR) and surface under the cumulative ranking curves (SUCRA) value.. Thirteen eligible RCTs including 7 drug therapies were included into this network meta-analysis. The network meta-analysis results showed that CI patients who received aspirin plus dipyridamole presented lower mortality when compared with those received aspirin plus clopidogrel (OR = 0.46, 95% CI = 0.18-0.99), indicating aspirin plus dipyridamole therapy had better efficacy for CI. As for intracranial hemorrhage (ICH), stroke recurrence, and adverse event (AE) rate, there were no significant differences of efficacy among 7 drug therapies. Besides, SUCRA values demonstrated that in the 7 drug therapies, aspirin plus dipyridamole therapy was more effective than others (mortality: 80.67%; ICH: 76.6%; AE rate: 90.2%).. Our findings revealed that aspirin plus dipyridamole therapy might be the optimum one for patients with CI, which could help to improve the survival of CI patients.

Topics: Aspirin; Cerebral Infarction; Cilostazol; Clopidogrel; Dipyridamole; Drug Therapy, Combination; Hematologic Agents; Humans; Intracranial Hemorrhages; Tetrazoles; Ticlopidine; Warfarin

We evaluated the dose-dependent efficacy, safety, and all-cause mortality of non-vitamin K antagonist oral anticoagulants (NOACs) in "atrial fibrillation (AF) patients who were OAC-naïve," or "AF patients with prior-stroke history" with those who were known to be high-risk subgroups under OAC.. After a systematic database search (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), five phase-III randomized trials comparing NOACs and warfarin in "OAC-naïve/OAC-experienced," or "with/without prior-stroke history" subgroups were included. The outcomes were pooled using a random-effects model to determine the relative risk (RR) for stroke/systemic thromboembolism (SSTE), major bleeding, intracranial hemorrhage, and all-cause mortality.. In conclusion, standard-dose NOAC showed lower all-cause mortality than warfarin in OAC-naïve patients with AF, and low-dose NOAC was better than warfarin among the patients with prior-stroke history in terms of all-cause mortality.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thromboembolism; Warfarin

The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, edoxaban, and rivaroxaban are administered in fixed doses without anticoagulant monitoring. Randomized trials show that unmonitored NOAC therapy is at least as effective as and safer than dose-adjusted warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Subgroup analyses indicate that plasma drug levels or anticoagulant activity of the NOACs predict stroke and bleeding. This review examines the historical basis for anticoagulant monitoring, discusses methods to measure and interpret drug levels, and critically assesses the role of routine laboratory monitoring in the management of NOAC therapy.. The predictable anticoagulant response of NOACs has provided the pharmacological basis for their administration in fixed doses without routine coagulation monitoring. Although it is possible to accurately measure NOAC drug levels, within-patient variability complicates interpretation of these results. Furthermore, patient characteristics, such as age and renal function, confound the association between NOAC drug levels and clinical outcomes. Information is lacking on the optimal drug level in particular patient groups (eg, elderly, the renally impaired, and those with high bleeding risk), the appropriate dose adjustment to achieve expected levels, and whether routine laboratory monitoring and dose adjustment will improve clinical outcomes. A benefit of a management strategy that incorporates routine therapeutic drug monitoring and dose adjustment over current standard-of-care metrics without such monitoring remains unproven.. Robust evidence from patients with atrial fibrillation randomized to NOACs or warfarin demonstrates that unmonitored NOAC therapy is at least as effective and safe as monitored warfarin, with lower rates of intracranial hemorrhage and reduced mortality. Further research is required to determine whether routine laboratory monitoring might provide a net benefit for patients. Until such data are available, clinicians should continue to prescribe NOACs in fixed doses without routine monitoring.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Chromatography, High Pressure Liquid; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Intracranial Hemorrhages; Partial Thromboplastin Time; Prothrombin Time; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Tandem Mass Spectrometry; Thiazoles; Thrombin Time; Warfarin

Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted.. Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk; Stroke; Ticlopidine; Treatment Outcome; Vitamin K; Warfarin

Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs.. We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods.. Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg).. Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Clinical Trials as Topic; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Markov Chains; Middle Aged; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Pyridines; Randomized Controlled Trials as Topic; Risk; Thiazoles; Warfarin

The original non-vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit-risk profiles of NOACs versus warfarin in AF patients with native valvular heart disease (VHD).. Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta-analytic summary hazard ratio (HR) and 95% confidence interval (CI) of efficacy and safety of NOACs versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with VHD. Pooling results from included trials showed that NOACs versus warfarin reduced stroke or systemic embolism (HR: 0.70; 95% CI, 0.60-0.82) and intracranial hemorrhage (HR: 0.47; 95% CI, 0.24-0.92) in AF patients with VHD. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95% CI, 0.69-0.91]; HR for intracranial hemorrhage: 0.33 [95% CI, 0.25-0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95% CI, 1.20-2.04]; HR for intracranial hemorrhage: 1.27 [95% CI, 0.77-2.10]).. Among patients with AF and native VHD, NOACs reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in VHD patients treated with rivaroxaban. NOACs are a reasonable alternative to warfarin in AF patients with VHD.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Female; Heart Valve Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8-2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Myocardial Infarction; Randomized Controlled Trials as Topic; Risk; Stroke; Warfarin

This study aims to assess the effect of warfarin resumption in patients who experienced warfarin-associated intracranial hemorrhage (ICH).. We conducted a systematic review and meta-analysis of studies evaluating the outcomes of adult patients who survived warfarin-associated ICH. We included studies that compared patients who resumed warfarin versus those who did not.. Of 3145 studies screened, ten observational studies were included in the final analysis. Death occurred in 181 of 968 patients (18.7%) who resumed warfarin and 834 of 2579 (32.3%) who did not resume warfarin (RR 0.51, 95% CI 0.34 to 0.76, P=0.0009). Ischemic stroke occurred in 32 of 902 (3.5%) patients who resumed warfarin and 172 of 2467 (7.0%) patients who did not resume warfarin (RR 0.56, 95% CI 0.39 to 0.82, P=0.002). Venous thromboembolism occurred in 4 of 224 (1.8%) patients who resumed warfarin and of 33 of 681 (4.8%) patients who did not resume warfarin (RR 0.39, 95% CI, 0.15 to 1.03, P=0.06). Recurrent ICH occurred in 200 of 2994 (6.7%) patients who resumed warfarin and 358 of 4652 (7.7%) patients who did not resume warfarin (RR 0.89, 95% CI 0.65 to 1.23, P=0.49).. The study suggests that warfarin resumption is associated with significant reduction in ischemic stroke and venous thromboembolism when compared to no warfarin resumption in patients who experience warfarin-associated ICH. Although these results are strongly supportive of restarting anticoagulation, prospective studies are required to confirm our results due to the high likelihood of bias in the included studies.

Topics: Female; Humans; Intracranial Hemorrhages; Male; Warfarin

The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin for stroke prevention in many patients with nonvalvular atrial fibrillation. Edoxaban, an oral factor Xa inhibitor, is the newest entrant in this class. Results of the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation (ENGAGE AF) study demonstrate that edoxaban is noninferior to warfarin for prevention of stroke and systemic embolic events, and is associated with significantly less major bleeding, including intracranial bleeding, and reduced cardiovascular mortality. With a net clinical benefit over warfarin, edoxaban is well positioned as a choice among the NOACs, which include dabigatran, rivaroxaban, and apixaban. But how will clinicians choose amongst them? The purpose of this paper is to (a) place the ENGAGE AF trial results into context with results of the studies with the other NOACs, and (b) aid clinicians in selection of the right anticoagulant for the right atrial fibrillation patient.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Research Design; Rivaroxaban; Stroke; Thiazoles; Warfarin

Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents.. A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84-1.01; P=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34-0.59; P<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01-1.50; P=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, ≥75 versus <75 years; β=1.53; 95% confidence interval, 1.10-2.14; P=0.020).. In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but-particularly among the elderly-a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial.

Topics: Age Factors; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Risk Factors; Stroke; Treatment Outcome; Warfarin

Several patients with non-valvular atrial fibrillation treated with warfarin or other vitamin-K antagonists (VKA) might benefit from switching to an oral non vitamin-K antagonist anticoagulant (NOAC). In the absence of randomised comparative trials of switching to NOACs versus maintaining VKA treatment, several considerations argue in favour of a switching strategy. First, there is conclusive evidence that haemorrhagic strokes and intracranial bleedings are much fewer in number with NOACs than with warfarin. The risk of intracranial bleeding is 52 % lower with NOACS than with warfarin, with extremes ranging from 33 to 70 %. Such benefit is applicable to different NOACs, and independent of the time-in-therapeutic range under warfarin. Patients at increased risk for intra-cranial bleeding (renal dysfunction, or prior stroke or intra-cranial bleeding) should benefit most from switching to NOACs. Patients with labile International Normalized Ratio are also considered good candidates for switching because of their increased risk of stroke, and the lack of interactions between the effects of NOACs versus warfarin and the time-in-therapeutic range. Furthermore, some NOACs proved to be superior to warfarin in reducing the risk of thromboembolic complications even in intention-to-treat analyses. As further advantage, NOACs show fewer drug-drug and drug-food interactions when compared with warfarin. Last, but not least, NOACs do not need frequent blood drawings except in patients with moderate renal dysfunction, in whom periodic controls of serum creatinine are generally advised. The higher cost remains a barrier to a wider use of NOACs, especially in low-income settings.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Evidence-Based Medicine; Female; Humans; Intracranial Hemorrhages; Male; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Severity of Illness Index; Survival Rate; Treatment Outcome; Vitamin K; Warfarin

The goal of this study was to compare the safety and effectiveness of individual antiembolic interventions in nonvalvular atrial fibrillation (AF): novel oral anticoagulants (NOACs) (apixaban, dabigatran, edoxaban, and rivaroxaban); vitamin K antagonists (VKA); aspirin; and the Watchman device.. A network meta-analysis of randomized, clinical trials (RCTs) was performed. RCTs that included patients with prosthetic cardiac valves or mitral stenosis, mean or median follow-up <6 months, <200 participants, without published report in English language, and NOAC phase II studies were excluded. The placebo/control arm received either placebo or no treatment. The primary efficacy outcome was the combination of stroke (of any type) and systemic embolism. All-cause mortality served as a secondary efficacy outcome. The primary safety outcome was the combination of major extracranial bleeding and intracranial hemorrhage. A total of 21 RCTs (96 017 nonvalvular AF patients; median age, 72 years; 65% males; median follow-up, 1.7 years) were included. In comparison to placebo/control, use of aspirin (odds ratio [OR], 0.75 [95% CI, 0.60-0.95]), VKA (0.38 [0.29-0.49]), apixaban (0.31 [0.22-0.45]), dabigatran (0.29 [0.20-0.43]), edoxaban (0.38 [0.26-0.54]), rivaroxaban (0.27 [0.18-0.42]), and the Watchman device (0.36 [0.16-0.80]) significantly reduced the risk of any stroke or systemic embolism in nonvalvular AF patients, as well as all-cause mortality (aspirin: OR, 0.82 [0.68-0.99]; VKA: 0.69 [0.57-0.85]; apixaban: 0.62 [0.50-0.78]; dabigatran: 0.62 [0.50-0.78]; edoxaban: 0.62 [0.50-0.77]; rivaroxaban: 0.58 [0.44-0.77]; and the Watchman device: 0.47 [0.25-0.88]). Apixaban (0.89 [0.80-0.99]), dabigatran (0.90 [0.82-0.99]), and edoxaban (0.89 [0.82-0.96]) reduced risk of all-cause death as compared to VKA.. The entire spectrum of therapy to prevent thromboembolism in nonvalvular AF significantly reduced stroke/systemic embolism events and mortality.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Warfarin

The management of stroke prevention among patients with atrial fibrillation (AF) has changed in the last few years. Despite the benefits of new oral anticoagulants (NOACs), decisions about the optimal agent remain a challenge. We provide a visual aid tool to guide clinicians and patients in the decision process of selecting oral anticoagulants for stroke prevention.. We created visual plots representing benefits of warfarin versus NOACs from a meta-analysis comprising 58,541 participants. Visual plots (Cates plots) were created using software available at nntonline.net. The primary outcome was stroke or systemic embolism during the study period.. In the chosen meta-analysis, 29,312 participants received a NOAC and 29,229 participants received warfarin. For every 1000 patients with AF, 38 would have a stroke or systemic embolic event in the warfarin group compared to 31 in the NOAC group (RR .81; 95% CI .73-.91). Fifteen patients would develop an intracranial hemorrhage in the warfarin group compared to 7 in the NOAC group (RR .48; 95% CI .39-.59). Conversely, 25 patients would develop gastrointestinal bleeding in the NOAC group compared to 20 in the warfarin group (RR 1.25; 95% CI 1.01-1.55).. For every 1000 treated individuals with AF, NOACs would prevent stroke or systemic embolism in 7 additional patients and cerebral hemorrhage in 8 additional patients compared to warfarin. On the other hand, 5 more patients would develop gastrointestinal bleeding with NOACs compared to warfarin. These data are visually shown in Cates plots, facilitating conversations with patients regarding anticoagulation decisions.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Audiovisual Aids; Decision Support Techniques; Embolism; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Odds Ratio; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Software; Stroke; Treatment Outcome; Warfarin

While evidence supports resumption of vitamin K antagonists (VKAs) among mechanical heart valve (MHV) patients presenting with anticoagulant-associated intracranial hemorrhage (ICH), ideal timing of resumption is uncertain.. To determine the optimal timing of VKA re-initiation and its associated clinical outcomes.. We performed a systematic review and a meta-analysis of studies published from January 1950 to August 2015. We extracted data on the location of initial ICH, use of cranial surgery, presence of atrial fibrillation, MHV type and position, number of MHVs, and timing of VKA resumption. Outcomes including valve thrombosis, thromboembolic events or ICH recurrence were recorded. Meta-regression analysis was conducting with controlling for covariates. We calculated absolute risks, and assessed the effect of anticoagulant resumption timing on ICH recurrence.. 23 case-series and case-reports were identified. Overall ICH recurrence was 13% (95% confidence interval [CI], 7%-25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3%-17%) and 12% (95% CI, 5%-23%) respectively. A trend towards lower ICH recurrence was observed with delayed VKA resumption (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with VKA resumption at 3days to 0% with resumption at 16days.. Among patients with MHV, there is inadequate data to suggest an optimal timing of VKA re-initiation following an ICH, though delayed restart appears to be protective against recurrence but is associated with higher risk of thrombosis. Our analysis suggests 4-7days might be an ideal time with least risk of thrombosis or ICH recurrence.

Topics: Anticoagulants; Heart Valve Prosthesis; Humans; Intracranial Hemorrhages; Thrombosis; Vitamin K; Warfarin

Oral anticoagulation is the cornerstone of stroke prevention in non-valvular atrial fibrillation (AF) and management of venous thromboembolism (VTE), resulting in a reduction in thrombotic complications and mortality. Benefit of vitamin K antagonists (VKAs) in such patients has been unambiguously confirmed, but VKA use is complicated by need for regular monitoring of the international normalized ratio and multiple drug and food interactions. Dabigatran is an oral direct thrombin inhibitor that can be used with fixed doses, without the need for routine anticoagulation laboratory monitoring and the advantage of few drug or diet interactions. Dabigatran is effective for stroke and systemic thromboembolism in AF and for the prophylaxis and treatment of VTE. The drug has a good safety profile and consistently shows a reduction in intracranial hemorrhage risk compared to warfarin. A specific reversal agent for dabigatran has been approved by FDA and EU. This review provides a summary of publications assessing clinical utility of dabigatran for different indications.

Topics: Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Humans; Intracranial Hemorrhages; Stroke; Venous Thromboembolism; Warfarin

Since 2009, four direct oral anticoagulants (DOACs) have been introduced for treatment of venous thromboembolism and stroke prevention in non-valvular atrial fibrillation. While they are currently first-line therapy for a majority of patients, there are a number of clinical situations where warfarin is preferable. In both randomised trials and real-world populations, use of DOACs significantly reduces the risk of intracranial haemorrhage as compared with warfarin. While drug-specific reversal agents are currently only available for dabigatran, andexanet alpha is pending approval for reversal of factor Xa inhibitors, reducing concerns about major bleeding for many patients and providers. DOACs can be held for 2-4 days prior to a procedure, depending on a patient's renal function, but should not be restarted too rapidly post-procedurally given their fast time to peak activity (∼2 hours). The anticoagulation clinic should play an important role in managing patients on all oral anticoagulation, both warfarin and DOACs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Drug Administration Schedule; Drug Monitoring; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Patient Selection; Predictive Value of Tests; Risk Factors; Stroke; Treatment Outcome; Venous Thromboembolism; Warfarin

Atrial fibrillation is found in a third of all ischaemic strokes, even more after post-stroke atrial fibrillation monitoring. Data from stroke registries show that both unknown and untreated or under treated atrial fibrillation is responsible for most of these strokes, which are often fatal or debilitating. Most could be prevented if efforts were directed towards detection of atrial fibrillation before stroke occurs, through screening or case finding, and treatment of all patients with atrial fibrillation at increased risk of stroke with well-controlled vitamin K antagonists or non-vitamin K antagonist anticoagulants. The default strategy should be to offer anticoagulant thromboprophylaxis to all patients with atrial fibrillation unless defined as truly low risk by simple validated risk scores, such as CHA2DS2-VASc. Assessment of bleeding risk using the HAS-BLED score should focus attention on reversible bleeding risk factors. Finally, patients need support from physicians and various other sources to start anticoagulant treatment and to ensure adherence to and persistence with treatment in the long term.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Medication Adherence; Registries; Risk Assessment; Risk Factors; Stroke; Vitamin K; Warfarin

This study investigated the efficacy and safety of novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart failure (HF) by a meta-analysis.. AF is quite prevalent in patients with HF.. Four phase III clinical trials comparing NOACs to warfarin in patients with AF were included. Each patient was defined as affected by HF according to the criteria of the trial in which the patient was enrolled. Pre-specified outcomes were the composite of stroke/systemic embolism (SSE); major, intracranial, and any bleeding; and cardiovascular (CV) and all-cause death.. A total of 55,011 patients were enrolled, 26,384 (48%) with HF, and 28,627 (52%) without HF; 27,518 receiving NOACs and 27,493 receiving warfarin (median, 70 years of age; 36% females; follow-up: 1.5 to 2.8 years). Rates of SSE (relative risk [RR]: 0.98; 95% confidence interval [CI]: 0.90 to 1.07]; p = 0.68) and major bleeding (RR: 0.95; 95% CI: 0.88 to 1.03; p = 0.21) were comparable in patients with and without HF. HF patients had reduced rates of any (RR: 0.86; 95% CI: 0.81 to 0.91; p < 0.01) and intracranial (RR: 0.74 95% CI: 0.63 to 0.88; p < 0.01) bleeding but increased rates of all-cause (RR: 1.70 95% CI: 1.31 to 2.19; p < 0.01) and CV death (RR: 2.05 95% CI: 1.66 to 2.55; p < 0.01). NOACs, compared with warfarin significantly reduced SSE and major, intracranial, and any bleeding, regardless of the presence or absence of HF (p. Patients with AF and HF had increased mortality but reduced rates of intracranial and any bleeding compared with the no-HF patients, with no differences in rates of SSE and major bleeding. NOACs significantly reduced SSE, major bleeding, and intracranial hemorrhage in HF patients. No interactions in efficacy and safety of NOACs were observed between AF patients with and without HF.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Dabigatran; Embolism; Factor Xa Inhibitors; Heart Failure; Hemorrhage; Humans; Intracranial Hemorrhages; Mortality; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Warfarin

Atrial fibrillation (AF) is the most common cardiac arrhythmia and predisposes patients to an increased risk of embolic stroke. After nearly 60 years, warfarin is no longer the only effective therapeutic option for patients with AF. Large randomized trials have consistently shown that non-vitamin K oral anticoagulants (NOACs) including dabigatran, rivaroxaban, apixaban, and edoxaban significantly reduce from the risk of intracranial hemorrhage (ICH) compared with warfarin. We provide a focused review regarding the NOACs and ICH in AF patients by summarizing findings of these large clinical trials, mechanisms of lower ICH, reversal strategies with specific agents, and monitoring strategies.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Coagulants; Drug Monitoring; Humans; Intracranial Hemorrhages; Predictive Value of Tests; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

A significant population of elderly Americans on warfarin is at risk for immediate and delayed intracranial hemorrhage. This qualitative systematic review ascertains the delayed intracranial hemorrhage risk associated with minor head injury and preinjury warfarin use.. A systematic review using MEDLINE, EMBASE, and the Cochrane Library was performed in August 2014. Cohort studies evaluating delayed intracranial hemorrhage in patients with minor head injuries on warfarin were eligible for inclusion. The definition of delayed hemorrhage was any intracranial bleeding detected subsequent to initial negative brain imaging result following the head injury. Three authors screened and abstracted the data and evaluated methodological quality. Data abstraction also included clinical characteristics that could identify risk factors for delayed intracranial hemorrhage.. The search retrieved 294 unique articles, of which 5 studies constituted the final review. The studies included data on 1,257 patients. Among higher-quality studies, the incidence of delayed intracranial hemorrhage ranged from 5.8 to 72 per 1,000 cases of patients on warfarin with minor head injury. Population age was an influential factor in this range of incident rates. International normalized ratio levels had no clear association with individual risk for delayed intracranial hemorrhage.. The incidence of delayed intracranial hemorrhage is low among patients on warfarin with minor head injury. Trauma centers should consider the characteristics of the population they serve compared with the published studies when determining management strategies for these patients.. Systematic review, level III.

Topics: Anticoagulants; Craniocerebral Trauma; Humans; Incidence; Intracranial Hemorrhages; Risk Assessment; Risk Factors; Time Factors; Warfarin

Central nervous system (CNS) hemorrhage is a potentially life-threatening condition, especially in patients with acquired coagulopathy. In this setting, treatment of CNS bleeding includes hemostatic therapy to replenish coagulation factors. There is currently a debate over the hemostatic efficacy of plasma in many clinical settings, alongside increasing concern about transfusion-associated adverse events. Despite these concerns, plasma is widely used. Moreover, plasma transfusion practice is variable and there is currently no uniform approach to treatment of traumatic, surgical or spontaneous CNS hemorrhage. This study addresses the need for guidance on the indications and potential risks of plasma transfusion in these settings. An Expert Consensus Panel was convened to develop recommendations guiding the use of plasma to treat bleeding and/or coagulopathy associated with CNS hemorrhage. The panel did not advise on the best treatment available but rather proposed recommendations to be used in the formulation of local procedures to support emergency physicians in their decision-making process.. Evidence was systematically gathered from the literature and rated using methods established by the Scottish Intercollegiate Guidelines Network. The evidence was used to develop graded consensus recommendations, which are presented along with the evidence-based rationale for each in this report.. Sixty-five articles were identified covering both vitamin K antagonist-anticoagulation reversal and treatment of bleeding/coagulopathy in non-anticoagulated patients. Recommendations were then developed in four clinical scenarios within each area, and agreed on unanimously by all members of the panel.. The Panel considered plasma to be reasonable therapy for CNS hemorrhage requiring urgent correction of coagulopathy, although physicians should be prepared for potential cardiopulmonary complications, and evidence suggests that alternative therapies have superior risk-benefit profiles. Plasma could not be recommended in the absence of hemorrhage or coagulopathy. Consideration of the absolute risks and benefits of plasma therapy before transfusion is imperative.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Component Transfusion; Humans; Intracranial Hemorrhages; Plasma; Practice Guidelines as Topic; Vitamin K; Warfarin

A short-cut review was carried out to determine whether the International Normalised Ratio (INR) value was a predictor of the risk of intracranial haemorrhage in patients taking warfarin after head injury. 796 papers were found using the reported search, of which eighteen were directly relevant. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses are shown in the accompanying table. It is concluded that level of the INR correlates poorly with the risk of haemorrhage and that the risk of haemorrhage remains significant even in patients with a sub-therapeutic INR.

Topics: Aged; Anticoagulants; Craniocerebral Trauma; Evidence-Based Emergency Medicine; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Predictive Value of Tests; Risk Factors; Warfarin

A short-cut review was carried out to determine whether patients on warfarin with a minor head injury can be discharged safely if they have a normal CT scan. 796 papers were found using the reported search, of which seven were considered relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses are shown in the accompanying table. It is concluded that the risk of delayed intracranial haemorrhage, at least in patients with an INR <3, is extremely small and discharge of these patients should be considered.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Craniocerebral Trauma; Evidence-Based Emergency Medicine; Female; Humans; Intracranial Hemorrhages; Patient Discharge; Radiography; Warfarin

Intracranial hemorrhage (ICH) affects 0.2-0.5 % of atrial fibrillation (AF) patients taking a novel oral anticoagulant (NOAC) each year. About two thirds of ICHs are intracerebral and one quarter subdural. The 30-day case fatality of NOAC-associated ICH was similar to that of warfarin-associated ICH in two trials. Consistent predictors of ICH are increasing age, a history of prior stroke or TIA, and concomitant use of an antiplatelet drug. Compared to warfarin, the NOACs significantly reduce the risk of ICH by half (risk ratio = 0.44; 95 % CI: 0.37 to 0.51). Compared to aspirin, apixaban has a similar risk of ICH (risk ratio = 0.84; 95 % CI, 0.38 to 1.87). Current treatments for NOAC-associated ICH include nonactivated and activated prothrombin complex concentrate, which reverse the anticoagulant effects of the NOACs, but their effects on bleeding and patient outcome are not known. Future treatments for NOAC-associated ICH promise to include specific antidotes to dabigatran (e.g., aDabi-Fab, PER977) and factor Xa inhibitors (e.g., r-Antidote PRT064445, PER977).

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Anticoagulants are effective at preventing and treating thrombosis, but can cause bleeding. For decades, vitamin K antagonists (VKAs) have been the only available oral anticoagulants. The development of non-VKA oral anticoagulants (NOACs), which inhibit either factor Xa or thrombin stoichiometrically, has provided alternatives to VKAs for several indications. The results of recent large-scale randomised controlled trials comparing NOACs with VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation (AF) have produced some unexpected results. As a group, NOACs showed similar efficacy as warfarin, but a reduced risk of major bleeding. The reduction in bleeding with NOACs was greatest with intracranial hemorrhage. In contrast, the relative risk of gastro-intestinal bleeding was increased with some NOACs. In this review, we explore the potential mechanisms as well as the implications of these organ-specific bleeding patterns.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Factors; Endothelium, Vascular; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intestinal Absorption; Intracranial Hemorrhages; Organ Specificity; Randomized Controlled Trials as Topic; Stroke; Thrombophilia; Thromboplastin; Vitamin K; Warfarin

In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K antagonists (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26 percent. Vitamin-K antagonists have a number of well documented shortcomings. Recently the results of randomised trials for three new oral anticoagulants that do not exhibit the limitations of vitamin-K antagonists have been published. These include direct factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide promising results for the new agents, including higher efficacy and a significantly lower incidence of intracranial bleeds compared with warfarin or aspirin. The new drugs show similar results in secondary as well as in primary stroke prevention in patients with AF. Apixaban was demonstrated to be clearly superior to aspirin and had the same rate of major bleeding complications. Meta-analyses show that the novel anticoagulants are superior to warfarin for the reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants add to the therapeutic options for patients with AF, and offer a number of advantages over warfarin, for both the clinician and patient, including a favorable bleeding profile and convenience of use. Aspirin is no longer an option in secondary stroke prevention in patients with atrial fibrillation. Consideration of these new anticoagulants will improve clinical decision making.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Guidelines as Topic; Humans; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Warfarin

The new oral anticoagulants (NOACs) dabigatran etexilate, rivaroxaban, and apixaban have been extensively studied for prevention and treatment of venous thromboembolic disease and for stroke prevention in atrial fibrillation. Elderly patients have the highest incidence of thrombotic complications but also have the highest risk of anticoagulant associated bleeding. In this review we critically examine the balance between risks and benefits of NOACs compared with vitamin K antagonists in elderly patients enrolled in phase 3 randomized controlled trials for the management of venous thrombosis and stroke prevention in atrial fibrillation. Results show that the favourable balance between risks and benefits of NOACs is preserved in the elderly population.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Drug Administration Schedule; Humans; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) is a common arrhythmia and the leading cause of stroke, an event with high human and economic burden. Novel oral anticoagulants have been approved in many markets as alternatives to warfarin for stroke prevention in patients with AF - dabigatran etexilate, apixaban and rivaroxaban. Given the high burden of AF, and given that new treatments can more effectively prevent stroke than warfarin, but at higher drug cost, there has been a need for systematic evaluation of the costs and benefits of these new treatments. In this study, we summarize the findings of a systematic literature review on the cost-effectiveness of the new oral anticoagulants. We find that there is substantial heterogeneity between the studies and their numerical findings, despite using a common set of four trials for their clinical inputs. However, there is broad consensus among them that each of the novel oral anticoagulants is cost-effective versus warfarin or aspirin.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Drug Administration Schedule; Humans; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Warfarin

Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).. Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively.. In patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban.. NOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk; Secondary Prevention; Stroke; Warfarin

There is clinical equipoise between warfarin and aspirin for stroke prevention in patients with heart failure in sinus rhythm (SR). The objective of this meta-analysis was to pool risk estimates for stroke, mortality, and intracerebral hemorrhage (ICH) from published clinical randomized controlled trials (RCTs).. MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched for English-language RCTs comparing warfarin to aspirin in heart failure through May 2012. Pooled relative risk (RR) was calculated from a random-effects model.. Four RCTs (n=3681) met the criteria for study inclusion. Warfarin was associated with a lower risk of stroke compared with aspirin (pooled RR, .59; 95% confidence interval [CI], .41-.85; P=.004). The number needed to treat (NNT) was 61. There was no difference between warfarin and aspirin in mortality (pooled RR, 1; 95% CI, .88-1.13), and ICH (pooled RR, 2.17; 95% CI, .76-6.24). Among secondary outcomes, warfarin was associated with almost twice the risk of major hemorrhage (pooled RR, 1.95; 95% CI, 1.37-2.76; P=.0001) compared with aspirin. The number needed to harm (NNH) was 34. There was no significant difference between warfarin and aspirin in risk of myocardial infarction (MI) (pooled RR, 1.02; 95% CI, .65-1.6], and heart failure exacerbation (HFE) (pooled RR, 1.11; 95% CI, .76-1.63).. Compared with aspirin, warfarin reduced the risk of stroke while conferring an increased risk of major hemorrhage. Warfarin does not increase mortality or confer an increased risk of ICH compared with aspirin.

Topics: Anticoagulants; Aspirin; Female; Heart Failure; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Warfarin

The risk-benefit profile of warfarin versus aspirin for patients with heart failure in normal sinus rhythm has not been definitively established. Our objective was to evaluate the overall comparative effects of warfarin and aspirin in patients with heart failure and normal sinus rhythm.. Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from January 1966 to June 2012 were searched to identify relevant studies. We included randomized controlled trials that included comparison of warfarin versus aspirin, and composite end point of death or stroke separately for active treatment and control groups. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects models. The search identified 4 randomized controlled trials of warfarin versus aspirin therapy, enrolling 3663 patients. There was no significant difference between the 2 treatments for the primary end point (warfarin versus aspirin: RR, 0.94; 95% CI, 0.84-1.06; P=0.31). Warfarin (versus aspirin) was associated with lower risk of any stroke (RR, 0.56; 95% CI, 0.38-0.82; P=0.003) and ischemic stroke (RR, 0.45; 95% CI, 0.24-0.86; P=0.02) but had a neutral effect on death (RR, 1.01; 95% CI, 0.89-1.14; P=0.89) and a higher risk of major bleeding (RR, 1.95; 95% CI, 1.37-2.76; P=0.0002).. Compared with aspirin, warfarin does not provide benefit in the prevention of stroke and death among patients with heart failure in sinus rhythm, but raises the risk of major bleeding; and therefore its use in these patients is not justified.

Topics: Anticoagulants; Aspirin; Chi-Square Distribution; Female; Fibrinolytic Agents; Heart Failure; Humans; Intracranial Hemorrhages; Male; Middle Aged; Patient Selection; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Warfarin

A best evidence topic in cardiac surgery was written according to the structured protocol. The question addressed was about the best time to restart anticoagulation in patients with intracranial bleed with a prosthetic valve in situ. This difficult clinical decision has to balance the risk of thromboembolism during the period that the anticoagulation was reversed and later withheld vs the risk of haematoma expansion or rebleed if the anticoagulation was started early. Altogether, more than 80 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. There were two prospective studies and eight retrospective studies. There were no randomized controlled trials on this topic. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Seven studies reported the strategy of reversal of anticoagulation with vitamin K, fresh frozen plasma or prothrombin concentrate. The emphasis was on prompt initial reversal of anticoagulation; however, the best agent for reversal was not defined. Four studies dealt exclusively with intracranial bleed in patients with prosthetic valve in situ. The remaining six studies on intracranial bleed had only a subset of patients with a prosthetic valve in situ. The anticoagulation was restarted with heparin and later switched to oral anticoagulant. Thromboembolic events during the period of reversal and cessation of anticoagulants were low (5%) as was the incidence of rebleed or haematoma expansion (0.5%). We conclude that anticoagulation can safely be withheld for a short period, up to 7-14 days in a patient with intracranial bleed with a very low probability of thromboembolic phenomenon. In patients with prosthetic valves, in situ anticoagulation in the form of heparin can safely be restarted as early as 3 days and switched to oral anticoagulation in the form of warfarin at 7 days without major concerns of bleeding.

Topics: Administration, Oral; Anticoagulants; Benchmarking; Blood Coagulation Factors; Drug Administration Schedule; Drug Substitution; Evidence-Based Medicine; Heart Valve Prosthesis Implantation; Heparin; Heparin Antagonists; Humans; Intracranial Hemorrhages; Plasma; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Warfarin and aspirin (acetylsalicylic acid [ASA]) are the most commonly used anticoagulant and antiplatelet drugs in the treatment of cardiovascular disease.. To provide a pooled estimate of the bleeding risk from randomized controlled trials (RCTs) comparing warfarin and ASA at the dose ranges recommended in evidence-based guidelines.. Ovid MEDLINE, Embase and the Cochrane Library, up to September 2011, were searched for RCTs comparing bleeding rates in adult patients randomized to warfarin, target International Normalized Ratio (INR) 2.0-3.5, and ASA, 50-650 mg daily, with at least 3 months of follow-up. Pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated with the inverse variance method and the random effects model.. Four thousand four hundred and forty-two abstracts were screened, resulting in eight included studies for final analysis. A pooled estimate derived from the 2904 patients enrolled indicated a trend towards an increase in major bleeding risk in those randomized to warfarin (OR 1.27; 95% CI 0.83-1.94). The pooled OR for intracranial hemorrhage in patients treated with warfarin vs. ASA was 1.64 (95% CI 0.71-3.78), and that for extracranial major bleeding was 1.03 (95% CI 0.61-1.75). Minor bleeding, from a 1748-patient sample, was more common in warfarin patients (OR 1.50; 95% CI 1.13-2.00).. This meta-analysis failed to find a statistically significant difference in major bleeding between warfarin, target INR 2.0-3.5, and ASA, 50-650 mg daily. The trend towards increased bleeding with warfarin appears to be explained by an excess of intracranial bleeding in warfarin patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation; Confidence Intervals; Evidence-Based Medicine; Female; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; Warfarin

Patients on warfarin are increasingly common in an ageing population. Previously published case series and cohort studies have resulted in conflicting conclusions with regard to the risk of fatal intracranial haemorrhage. The aim of this study was to undertake a meta-analysis in order to compare the mortality rate of anticoagulated head injured patients against the mortality rate of head injured patients not on coumarin anticoagulation.. The databases Medline and EMBASE were searched via the ovid interface. The initial search strategy returned 364 results. A second search was performed using Pubmed to identify possible abstracts missed by the first search. Forty-seven full articles were reviewed if the abstract suggested that they were either case control studies or nested case control studies comparing the mortality rate of anticoagulated head injured patients against the mortality rate of head injured patients not on coumarin anticoagulation.. Eleven papers were identified, which met the criteria for the meta-analysis. Despite the heterogeneity between the studies (Q test: 27.421, 10 DF, P = 0.002), the fixed effects model may be the preferred model based on the fact that 10 out of the 11 studies had an odds ratio greater than one. The fixed effects model produced a common odds ratio for death in anticoagulated patients with blunt head trauma of 2.008 (95% CI 1.634 - 2.467).. The results of this meta-analysis has shown that the cohort of patients who are anticoagulated and suffer blunt head trauma appear to have an increased risk of death compared to a similar cohort of head injured patients who are not anticoagulated.

Topics: Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Epidemiologic Methods; Humans; Intracranial Hemorrhages; Warfarin; Wounds, Nonpenetrating

It is uncertain whether thrombolytic therapy is safe in patients with acute ischaemic stroke who are treated with warfarin and have a subtherapeutic international normalised ratio (INR) at stroke onset.. The authors performed a systematic review of the literature and included studies that assessed the relation between prior warfarin use with subtherapeutic INR and outcome after intravenous or intra-arterial thrombolytic therapy in acute ischaemic stroke. Outcome measures were symptomatic intracranial haemorrhage (SICH), modified Rankin scale score 0-2 and mortality. Second, the authors performed a meta-analysis of the included studies.. Seven studies with 3631 patients were included. 240 (6.6%) patients used warfarin before stroke onset. The risk of SICH was increased in the warfarin group (OR 2.6; 95% CI 1.1 to 5.9. p=0.02). There was no significant difference, however, in functional outcome (OR 0.9; 95% CI 0.6 to 1.2, p=0.32) or death from all causes (OR 1.2; 95% CI 0.9 to 1.8).. The risk of SICH after thrombolytic therapy is increased in patients using warfarin with subtherapeutic INR levels. The authors found no evidence of an increase in death from all causes or worsening of functional outcome in warfarin treated patients.

Topics: Brain Ischemia; Clinical Trials as Topic; Humans; International Normalized Ratio; Intracranial Hemorrhages; Stroke; Thrombolytic Therapy; Warfarin

Patients with acute coronary syndrome (ACS) continue to be at risk for recurrent ischemic events, despite an early invasive strategy and the use of dual antiplatelet therapy. The anticoagulant pathway remains activated for a prolonged period after ACS and, consequently, has been a target for treatment. Early studies with warfarin indicated its benefit, but the risk of bleeding and the complexities of warfarin anticoagulation resulted in little use of this strategy. Rivaroxaban, apixaban, and dabigatran are new specific inhibitors of anticoagulant factors (Xa or IIa) currently available for the prevention of thrombosis and/or thromboembolism. Thus far, studies with dabigatran and apixaban in ACS have shown no clinical benefit and bleeding has been increased. The ATLAS ACS 2-TIMI 51 trial observed the impact of rivaroxaban 2.5 mg and 5 mg twice daily in patients with recent ACS receiving current management (both early invasive strategy and dual antiplatelet therapy with aspirin and clopidogrel) over a follow-up period of over 1 year. Rivaroxaban 2.5 mg twice daily reduced cardiovascular death, myocardial infarction, or stroke by 16%, and both cardiovascular and all-cause mortality by approximately 20%. Although major bleeding increased from 0.6% to 2.1% and intracranial hemorrhage from 0.2% to 0.6%, there was no increase in fatal bleeding. The role of rivaroxaban in the management of ACS is discussed in this review. The reduction in mortality is the main finding that could lead to the use of rivaroxaban in the management of ACS in high-risk individuals with a low bleeding risk.

Topics: Acute Coronary Syndrome; Anticoagulants; Dose-Response Relationship, Drug; Hemorrhage; Humans; Intracranial Hemorrhages; Morpholines; Risk; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis; Warfarin

Warfarin-related intracranial hemorrhage carries a high mortality and poor neurological outcome. Rapid reversal of coagulopathy is a cornerstone of medical therapy to halt bleeding progression; however the optimal approach remains undefined. Prothrombin complex concentrates have promising features that may rapidly reverse coagulopathy, but remain relatively unstudied. We aim to review the literature regarding the use of prothrombin complex concentrates in patients with warfarin-related intracranial hemorrhage. A comprehensive review of the literature was conducted using PUBMED and Google Scholar databases to identify the use of PCC in patients with warfarin-related intracranial hemorrhage. The characteristics abstracted included the type of PCC, dosing, study design, type of intracranial hemorrhage, changes in the INR, and adverse effects. Prothrombin complex concentrates are heterogeneous in regards to factor concentration. PCC consistently reversed the INR in patients with intracranial hemorrhage. There is some evidence that PCC may reverse the INR more rapidly compared to fresh frozen plasma. Serious adverse effects were uncommon and included mainly thromboembolism. PCC has features which make it a promising therapy for patients with warfarin-related intracranial hemorrhage, and deserves more rigorous study in prospective-randomized controlled trials.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Factors; Dose-Response Relationship, Drug; Humans; International Normalized Ratio; Intracranial Hemorrhages; Plasma; Platelet Count; Prothrombin Time; Randomized Controlled Trials as Topic; Thrombin Time; Thromboembolism; Warfarin

There is little systematically derived evidence-based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma.. A systematic review (SR) and meta-analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence-based plasma transfusion guidelines as well as identify areas for future investigation.. Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients.. We have systematically developed evidence-based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion.

Topics: Anticoagulants; Blood Component Transfusion; Evidence-Based Medicine; Humans; Intracranial Hemorrhages; Plasma; Warfarin

The decline in stroke incidence and mortality in the U.S. over the past 20 years is reaching a plateau, and the number of strokes may actually start to increase as the population ages. However, recent clinical trials have demonstrated that there are numerous opportunities to improve stroke prevention strategies and also opportunities to effectively intervene in and treat acute strokes. For patients with diabetes and for those with prior strokes or transient ischemic attacks, it has become evident that aggressive low-density lipoprotein lowering with statin medications will decrease the risk for total and fatal strokes. Optimal anticoagulation and antiplatelet therapy for primary and secondary stroke prevention in atrial fibrillation is being carefully defined. With numerous novel factor Xa and direct thrombin inhibitor drugs completing phase III clinical trials, it is likely that additional oral anticoagulant drugs will be clinically available for stroke prevention soon. Additionally, a major clinical trial is nearing completion that may resolve the role of carotid stenting and carotid endarterectomy in primary and secondary stroke prevention. There are recent notable advances in the acute treatment of stroke. It is likely that the time window for thrombolysis for appropriate patients with strokes will be increased from 3 to 4.5 h, permitting the inclusion of more patients in this treatment approach. There is ongoing investigation of intra-arterial thrombolysis and of acute intra-arterial thrombus extraction for treatment of selected patients with strokes. Unlike the progress in treatment of ischemic strokes, treatment of hemorrhagic stroke is progressing more slowly.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cholesterol, LDL; Diabetic Angiopathies; Endarterectomy, Carotid; Foramen Ovale, Patent; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; International Normalized Ratio; Intracranial Hemorrhages; Stents; Stroke; Thrombectomy; Thrombolytic Therapy; Thrombosis; United States; Warfarin

Stroke is the third leading cause of mortality and is one of the leading cause of disability in the world today. Although underused, anticoagulation with warfarin is still the treatment of choice for prevention of stroke in patients with AF, though hemorrhage is clearly increased in the anticoagulated patient. The substantial difficulties associated with warfarin use give reasons for the continuing challenge of decision making about antithrombotic therapy. They have led to a search for alternative approaches of stroke prophylaxis resulting in a strategy of mechanically sealing the left atrial appendage (LAA) and excluding it from the systemic circulation. A couple of years ago a percutaneous transcatheter transseptal approach to LAA occlusion has become feasible. Since then, valuable technical knowledge and a proof of concept emerged from clinical trials using three different systems. However, also the intervention bears a risk. Thus, identifying those patients who gain the most from either therapy is crucial which, in the first line, means to calculate the risk of stroke or bleeding. Unfortunately, patients with some defined comorbidities are at risk of both, cerebral embolism or hemorrhage. Whether this target group may benefit from LAA occlusion is a matter of this discussion.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Balloon Occlusion; Cardiac Catheterization; Clinical Trials as Topic; Female; Humans; Intracranial Hemorrhages; Male; Risk; Stroke; Warfarin

Spontaneous intracerebral haemorrhage is one of the most feared complications of long-term anticoagulation. Warfarin therapy not only increases the likelihood of suffering an intracranial haemorrhage, but also increases the mortality associated with it. This review aims to examine the incidence, pathogenesis, and outcome following a warfarin associated intracranial haemorrhage. It also evaluates the available evidence regarding optimal management of these patients, including timing and strategies for reversal of the coagulopathy, the role of neurocritical care and surgery, and indications for re-anticoagulation once the acute phase has past. The specific management of patients with prosthetic heart valves is also discussed. A summary of current societal guidelines is also included, as are some key practice points.

Topics: Anticoagulants; Blood Coagulation Factors; Factor VIIa; Humans; Incidence; Intracranial Hemorrhages; Recombinant Proteins; Vitamin K; Warfarin

To report a case of fatal intracranial bleeding possibly due to an interaction between warfarin and inactivated influenza vaccination.. A 64-year-old white male was admitted to the hospital after becoming unresponsive. The family reported a 2-day history of bleeding from the patient's rectum prior to admission. He had no recent changes in medical conditions or medication regimen, which included warfarin for stroke prophylaxis secondary to atrial fibrillation. The patient had received an inactivated influenza vaccine 4(1/2) weeks prior to presentation, at which time his international normalized ratio (INR) was 2.0. Upon admission, the patient's INR was greater than 15; INR values over the previous 6 months had been relatively stable (range 1.4-4.7). A noncontrast computed tomography scan of the head showed a large parenchymal hemorrhagic infarction involving the left temporal, parietal, and occipital lobes. In the emergency department, the patient received a nitroglycerin infusion to maintain systolic blood pressure in the range of 140-160 mm Hg as well as an infusion of 4 units of fresh frozen plasma and 10 mg of vitamin K. Following a neurosurgery evaluation, it was determined that nothing meaningful could be done to alter the patient's outcome positively, and he died approximately 17 hours after admission.. To date, most reports of concomitant warfarin therapy and influenza vaccination indicate no significant change in average anticoagulation parameters. However, there are reports of individuals who may have experienced increased anticoagulation following influenza vaccination. The reason for these increases is unknown, but may involve only certain components of the vaccine, which is altered almost annually. Our patient's significant INR elevation, after being relatively stable for at least 6 months, was thought to be due to an interaction between warfarin and the influenza vaccination. The Horn Drug Interaction Probability Scale indicated a possible interaction between warfarin and the influenza vaccination.. Considering the outcome in our patient, as well as outcomes in other individuals who have experienced an increased INR in a similar scenario, it appears justified to implement more frequent INR evaluations during the 4-6 weeks following influenza vaccination.

Topics: Drug Interactions; Fatal Outcome; Humans; Influenza Vaccines; Intracranial Hemorrhages; Male; Middle Aged; Warfarin

Intracranial haemorrhage is a life-threatening complication of anticoagulation. When the anticoagulation is for a mechanical heart valve the risks of further bleeding on warfarin need to be balanced against the risks of thromboembolism from an unprotected valve.

Topics: Aged; Anticoagulants; Female; Heart Valve Prosthesis; Humans; Intracranial Hemorrhages; Male; Risk Factors; Thromboembolism; Warfarin

Stroke remains an increasing worldwide cause of disability and mortality, and it is the second leading cause of death in industrialized countries. Patients with atrial fibrillation form a unique group with increased risk of cardioembolic stroke. Despite the widespread application of the National Institutes of Health stroke scale and guidelines, patients with atrial fibrillation represent a clinically challenging group that deserves a special approach during the acute stroke phase. The mechanism of stroke in these patients is either cardioembolic [especially with an international normalized ratio (INR) < 2.0] or hemorrhagic (especially with INR > 5.0) (Figure 1). Atrial fibrillation with valvular heart disease significantly increases the risk for ischemic stroke. Specifically, patients with mitral stenosis who develop atrial fibrillation increase their risk of cardioembolism by 3 to 7 times. Many patients with atrial fibrillation still develop ischemic or hemorrhagic stroke despite appropriate use of anticoagulation. Prior stroke, transient ischemic attacks, congestive heart failure, hypertension, age > 75, and diabetes mellitus are all well-established risk factors for the development of stroke in patients with atrial fibrillation. The CHADS-2 score is the most widely studied and clinically used method for stratifying patients with nonrheumatic atrial fibrillation. In our review, we present the most recent clinical guidelines and trends for the approach to and management of this patient group.

Topics: Anticoagulants; Antifibrinolytic Agents; Aspirin; Atrial Fibrillation; Factor VIIa; Heparin; Humans; Intracranial Hemorrhages; Plasma; Recombinant Proteins; Stroke; Thrombolytic Therapy; Vitamin K; Warfarin

To evaluate data addressing use of anticoagulation in elderly patients with atrial fibrillation (AF), in particular those at risk of falls.. Primary literature was identified through PubMed MEDLINE (1966-December 2007) and EMBASE (1980-December 2007) using the search terms anticoagulation, warfarin, aspirin, elderly, falls, older persons, atrial fibrillation, bleeding, education, stroke, and use. Additional references were obtained through review of references from articles obtained.. Clinical studies evaluating warfarin and aspirin efficacy in AF, as well as studies evaluating anticoagulation and falls, elderly patients, and bleeding were considered for inclusion. Selection emphasis was placed on randomized studies of AF and those evaluating anticoagulation and falls.. Uncertainties over the optimal treatment for elderly patients with AF still exist. Variance in the guidelines is reflected in current practice, as some discrepancies are present. Warfarin is underprescribed in elderly patients, with only about 50% of eligible patients receiving therapy. Falls are most often cited as the reason for not using anticoagulants in an elderly patient. Three risk-benefit analyses have been performed, and all found that despite risks associated with warfarin, its benefits outweigh its risks even in patients who fall. Warfarin should be used rather than aspirin or no therapy in elderly patients at risk of falls. Anticoagulation education has been shown to reduce the risk of bleeding in the elderly and should be a vital part of warfarin management.. The risk of falls alone should not automatically disqualify a person from being treated with warfarin. While falls should not dictate anticoagulant choice, assessment and management of fall risk should be an important part of anticoagulation management. Efforts should be made to minimize fall risk.

Topics: Accidental Falls; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Stroke; Warfarin

The article is based upon two adverse drug reaction reports after switch from atorvastatin to simvastatin. Simvastatin interactions with warfarin and the cytochrome P450-3A4 inhibitor diltiazem were suspected as possible causes of the events (fatal intracranial haemorrhage with INR > 8 and myopathy). Relevant literature was examined to evaluate potential differences in atorvastatin and simvastatin interaction profiles.. Relevant interaction studies were identified through searches in the databases PubMed and ISI Web of Knowledge. Interaction databases referring to primary sources and product monographs were also examined.. One interaction study was found for the warfarin-atorvastatin combination, but this showed no relevant changes in prothrombin time. Three interaction studies were identified for the combination warfarin-simvastatin and these showed consistently increased INR and/or reduced dose requirements for warfarin (10-30%) after starting treatment with simvastatin. Three studies had investigated the degree to which simvastatin and atorvastatin interact with a CYP3A4 inhibitor in the same population. In these studies, plasma concentrations of both statins increased, but the increases were several times greater for simvastatin than for atorvastatin.. Interaction studies show that atorvastatin and simvastatin display differences in interaction potential toward warfarin and drugs inhibiting CYP3A4 metabolism. It is important to consider the risk of interactions when switching to or starting simvastatin treatment.

Topics: Anticholesteremic Agents; Anticoagulants; Antihypertensive Agents; Aryl Hydrocarbon Hydroxylases; Atorvastatin; Diltiazem; Drug Interactions; Drug Therapy, Combination; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intracranial Hemorrhages; Muscular Diseases; Pyrroles; Risk Factors; Simvastatin; Warfarin

Dangerous Interactions Involving Antibiotic Use In Warfarin-Treated Nursing Facility Residents FACTS OF THE INCIDENT: All names, places and dates and some details have been changed to protect the confidentiality of this actual event.

Topics: Accidental Falls; Aged; Anti-Infective Agents, Urinary; Anticoagulants; Confusion; Drug Monitoring; Drug Synergism; Drug Therapy, Combination; Female; Geriatrics; Humans; International Normalized Ratio; Intracranial Hemorrhages; Malpractice; Nursing Homes; Organizational Policy; Prothrombin; Risk Management; Total Quality Management; Trimethoprim, Sulfamethoxazole Drug Combination; Warfarin

Although randomized controlled trials (RCTs) are conducted to establish whether novel interventions work on average in the patient population, there is a growing desire to move to a more individualized approach to evaluation. The potential benefits and harms of a treatment policy may differ between individuals. If these benefits and harms are not evaluated distinctly, and in a quantitative framework, transparency can be lost in the decision-making process.. Glasziou and Irwig have outlined the concept of net clinical treatment benefit for identifying the patients for whom the potential benefits of treatment outweigh the possible side effects. This study revisits the decision whether to use warfarin to treat atrial fibrillation. In this analysis, RCT and various sorts of observational data are synthesized.. This reanalysis brings into question the conclusions of the original analysis on who would benefit from warfarin; however, caution is advised, due to limitations in the quality of life data available.. A fully realized Bayesian implementation of the model is presented. This provides a framework for including uncertainty related to the estimation of all model parameters, and permits both direct probability statements and credible intervals for specific patient groups to be expressed.

Topics: Anticoagulants; Atrial Fibrillation; Bayes Theorem; Decision Support Techniques; Evidence-Based Medicine; Humans; Intracranial Hemorrhages; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Warfarin

Warfarin is the most commonly used oral anticoagulant in the UK. It is associated with few side effects apart from haemorrhage. The most appropriate way to reverse the anticoagulant effect of warfarin depends on the clinical circumstances. In serious bleeding, rapid reversal is required, whereas in minor bleeding or asymptomatic over anticoagulation, a more leisurely approach is usually appropriate. This review discusses the current approaches to warfarin reversal in clinical practice. The development of a uniform approach to warfarin reversal in the Northern Region is described.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Child; Coagulants; Drug Administration Schedule; Factor VII; Factor VIIa; Hemorrhage; Humans; Intracranial Hemorrhages; Plasma; Practice Guidelines as Topic; Recombinant Proteins; Vitamin K; Warfarin

Situations often occur in anticoagulated patients that require adjustment of anticoagulation therapy. These situations often place the patient at risk of bleeding, and often there is little clinical data to guide the clinician. This paper reviews several of these situations and offers guidance for the management of patients. The problems reviewed concern the patient on anticoagulants who is or desires to get pregnant, peri-operative management of anticoagulated patients, anticoagulated patients with intracranial bleeding or endocarditis, and the "warfarin refractory" patient.

Topics: Anticoagulants; Drug Interactions; Endocarditis; Female; Humans; Intracranial Hemorrhages; Pregnancy; Pregnancy Complications, Cardiovascular; Surgical Procedures, Operative; Warfarin

The aim of this study has been twofold: 1--to examine the impact of oral anticoagulant (OAC) use on a possible recent rise in the admission rate of intracerebral haemorrhages to Aberdeen Royal Infirmary (ARI), and 2--to estimate the absolute risk of intracranial haemorrhage for outpatients followed up in the OAC Clinic at ARI. The number of patients admitted to ARI with intracerebral bleedings increased by 60% between 1993 and 1998. A corresponding increase in the proportion of patients with concurrent OAC use (4.7% vs 15.7%, p = 0.055) cannot sufficiently explain the increase in the total number of intracerebral haemorrhages. The average annual incidence of intracranial haemorrhages for the OAC Clinic at ARI is found to be acceptably low at 0.33% per year. Further audit of the large number of patients receiving warfarin outwith the supervision of the clinic is urgently required.

Topics: Administration, Oral; Anticoagulants; Chi-Square Distribution; Hospital Mortality; Humans; Incidence; Intracranial Hemorrhages; Risk Factors; Scotland; Tomography, X-Ray Computed; Warfarin

The aim of this study was to compare the clinical course and radiological features of oral anticoagulant (OAC)-related intracranial haemorrhages with those of haemorrhages unrelated to OAC use admitted over the last six years to a tertiary care centre in the North of Scotland. We furthermore wished to determine the measures taken for reversal of OAC therapy and the resulting short-term outcome. Sixty-eight patients had been treated with OACs at the time of intracranial haemorrhage (32% subdural, 62% intracerebral). Patients admitted with OAC-related and unrelated haemorrhages did not differ significantly in any of the clinical features considered. On CT scan, there was no significant difference according to OAC use in the mean size of subdural (depth 15 +/- 5 vs. 18 +/- 8 mm, p = 0.36), or intracerebral haematomas (max. diameter 40 +/- 21 vs. 41 +/- 20 mm, p = 0.73). No reversal measures were taken in 38% of OAC-treated patients. In-hospital mortality was significantly higher for OAC-related haemorrhages compared to unrelated haemorrhages (38% vs. 18%, p = 0.001). To further elucidate the effects of anticoagulant reversal on the outcome of OAC-related intracranial haemorrhages, a large-scale prospective study is warranted.

Topics: Anticoagulants; Glasgow Coma Scale; Hospital Mortality; Humans; Intracranial Hemorrhages; Radiography; Treatment Outcome; Warfarin

Falls are always a concern regarding the balance of risk/benefit in patients with atrial fibrillation treated with anticoagulants. In this analysis, we aimed to evaluate the outcomes of patients that had a fall/head injury reported in the RE-LY clinical trial (Randomized Evaluation of Long-Term Anticoagulation Therapy) and to explore the safety of dabigatran (a nonvitamin K antagonist oral anticoagulant).. We performed a post hoc retrospective analysis of intracranial hemorrhage and major bleeding outcomes in the RE-LY trial with 18 113 individuals with atrial fibrillation, according to the status occurrence of falls (or head injury) reported as adverse events. Multivariate Cox regression models were used to provide adjusted hazard ratio (HR) and 95% CI.. In the study, 974 falls or head injury events were reported among 716 patients (4%). These patients were older and had more frequently comorbidities such as diabetes, previous stroke, or coronary artery disease. Patients with fall had a higher risk of major bleeding (HR, 2.41 [95% CI, 1.90-3.05]), intracranial hemorrhage (HR, 1.69 [95% CI, 1.35-2.13]), and mortality (HR, 3.91 [95% CI, 2.51-6.10]) compared to those who did not have reported falls or head injury. Among patients who had falls, those allocated to dabigatran showed a lower intracranial hemorrhage risk (HR, 0.42 [95% CI, 0.18-0.98]) compared with warfarin.. In this population, the risk of falls is important and confers a worse prognosis, increasing intracranial hemorrhage, and major bleeding. Patients who fell and were under dabigatran was associated with lower intracranial hemorrhage risk than those anticoagulated with warfarin, but the analysis was merely exploratory.

Topics: Accidental Falls; Anticoagulants; Atrial Fibrillation; Craniocerebral Trauma; Dabigatran; Hemorrhage; Humans; Intracranial Hemorrhages; Retrospective Studies; Stroke; Warfarin

Patients experiencing an intracranial hemorrhage (ICH) on oral anticoagulants often require rapid reversal. This study evaluated patients taking factor Xa inhibitors or warfarin that received reversal with 4-factor prothrombin complex concentrate (4F-PCC) for an ICH. The objective of the study was to determine if the efficacy of 4F-PCC for the reversal of factor Xa inhibitors is noninferior to its use in warfarin reversal in patients with ICH.. This was a retrospective, single center, noninferiority trial. Patients presenting to the emergency department with ICH were divided into two cohorts: those taking factor Xa inhibitors versus those taking warfarin. In each cohort, patients received anticoagulation reversal with weight-based 4F-PCC. The primary endpoint was hemostatic efficacy defined as ≤20% expansion in hematoma volume on repeat computed tomography imaging. A pre-specified noninferiority margin of -10% was selected to evaluate the difference between groups for the primary endpoint.. A total of 221 patients were included in the study (factor Xa inhibitors, n = 87; warfarin, n = 134). Effective hemostasis was achieved in 70 patients (81%) on factor Xa inhibitors compared to 111 patients (83%) on warfarin, (-2.4% difference, [95% confidence interval, -12.87 to 8.12]; p = 0.654). There was no statistically significant difference between groups with regards to the primary outcome; however, the use of 4F-PCC in factor Xa inhibitor reversal was not noninferior when compared to 4F-PCC use for warfarin reversal. Hospital length of stay and discharge disposition were similar between cohorts.. The efficacy of 4F-PCC in reversing factor Xa inhibitor-related ICH compared to warfarin-related ICH was not significantly different between groups; however, these results did not prove noninferiority. Further study is warranted to delineate 4F-PCC's role in reversing factor Xa inhibitors in patients with ICH.

Topics: Anticoagulants; Blood Coagulation Factors; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemostasis; Hemostatics; Humans; Intracranial Hemorrhages; Retrospective Studies; Warfarin

Intracranial hemorrhage (ICH) is a known risk of oral anticoagulation; delineating ICH attributes may provide nuanced guidance regarding atrial fibrillation management. We evaluated ICH characteristics and outcomes from Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48), a randomized trial that compared two edoxaban regimens (higher-dose edoxaban regimen 60/30 mg (HDER), lower-dose edoxaban regimen 30/15 mg (LDER)) with warfarin in patients with atrial fibrillation. Patients who suffered ICH vs those who did not were compared and independent predictors of ICH were calculated. We also assessed ICH subtype and etiology. Of 21,105 randomized patients, 322 (1.53%) had ≥ 1 ICH for a total of 368 events. Intraparenchymal hemorrhage (HDER: HR 0.52 [95% CI 0.35-0.77], LDER: HR 0.22 [0.13-0.38]) and subdural hematoma (HDER: HR 0.29 [0.15-0.55], LDER: HR 0.26 [0.13-0.50]) were lower with both HDER and LDER vs warfarin. Subarachnoid hemorrhage frequency was similar in the HDER vs warfarin groups but lower in LDER. Compared to warfarin, edoxaban was associated with lower risk of spontaneous ICH (HDER: HR 0.47 [0.31-0.69], LDER: HR 0.34 [0.22-0.53]) and traumatic ICH (HDER: HR 0.32 [0.17-0.61], LDER: HR 0.31 [0.16-0.59]). In multivariable analysis, randomization to warfarin, increased age, and risk of falling remained independent predictors of ICH. In ENGAGE AF-TIMI 48, ICH was decreased in edoxaban-treated patients compared to warfarin-treated patients, including ICH of both spontaneous and traumatic causes. Both edoxaban regimens lowered intraparenchymal and subdural hemorrhages compared to warfarin. Patient characteristics and medical history may help guide anticoagulation management.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyridines; Thiazoles; Warfarin

This study compares the safety and efficacy of a fixed dose of 4-factor prothrombin complex concentrate (4FPCC) to the FDA-approved variable dosing for reversal of warfarin-induced anticoagulation.. This was a single-center, prospective, open-label, randomized controlled trial with subjects randomized to 4FPCC at a fixed dose of 1500 IU or the FDA-approved variable dosing regimen. The primary efficacy outcome (reversal success) was defined as a post-intervention international normalized ratio (INR) of less than or equal to 1.5. Given that 4FPCC is the standard of care for reversal of warfarin-induced anticoagulation an active-controlled approach was employed with the two dosing regimens compared based on efficacy, cost, and safety outcomes.. 71 subjects (34 in the fixed dose group and 37 in the variable dose group) completed the study. There were no significant differences in age, gender, weight, initial INR, or indication for 4FPCC administration between the two treatment groups. Reversal success in the fixed-dose group was 61.8%, while in the variable dose group reversal success was 89.2%. Reversal success in the fixed-dose group was significantly lower than the rate of reversal success in the variable dose group (27.4% lower, p = 0.011).. The results of this study provide evidence that fixed dosing results in lower reversal success rates as compared to variable dosing of 4FPCC for warfarin-induced anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Emergencies; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Warfarin

A history of gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) may impact decisions about anticoagulation treatment. We sought to determine whether prior GIB in patients with AF taking anticoagulants was associated with an increased risk of stroke or major hemorrhage.. We analyzed key efficacy and safety outcomes in patients with prior GIB in ARISTOTLE. Centrally adjudicated outcomes according to GIB history were analyzed using Cox proportional hazards models adjusted for randomized treatment and established risk factors.. In patients with AF on oral anticoagulants, prior GIB was associated with an increased risk of subsequent major GIB but not stroke, intracranial bleeding, or all-cause mortality. For the key outcomes of stroke, hemorrhagic stroke, death, and major bleeding, we found no evidence that the treatment effect (apixaban vs. warfarin) was modified by a history of GIB.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Mortality; Proportional Hazards Models; Pyrazoles; Pyridones; Risk; Risk Factors; Severity of Illness Index; Stroke; Treatment Outcome; Warfarin

Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races.. There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20-25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively).. Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.

Topics: Aged; American Indian or Alaska Native; Anticoagulants; Asian People; Atrial Fibrillation; Black People; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Proportional Hazards Models; Pyridines; Stroke; Thiazoles; Treatment Outcome; Warfarin; White People

The outcomes of patients developing major bleeding while on oral anticoagulants remain largely unquantified. The objectives of this study were to: (i) describe the burden of major hemorrhage associated with all available oral anticoagulants in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital mortality and duration of hospitalization following major bleeding; (ii) identify risk factors for mortality; and (iii) compare the characteristics of major hemorrhage between cases treated with warfarin and direct oral anticoagulants for the subgroups of patients with atrial fibrillation or venous thromboembolism. This was a multicenter, 3-year prospective cohort study of patients aged ≥18 years on oral anticoagulants who developed major hemorrhage leading to hospitalization. The patients were followed up for 30 days or until discharge or death, whichever occurred first. In total 2,192 patients (47% female, 81% on warfarin, median age 80 years) were reported between October 2013 and August 2016 from 32 hospitals in the UK. Bleeding sites were intracranial (44%), gastrointestinal (33%), and other (24%). The in-hospital mortality was 21% (95% CI: 19%-23%) overall, and 33% (95% CI: 30%-36%) for patients with intracranial hemorrhage. Intracranial hemorrhage, advanced age, spontaneous bleeding, liver failure and cancer were risk factors for death. Compared to warfarin-treated patients, patients treated with direct oral anticoagulants were older and had lower odds of subdural/epidural, subarachnoid and intracerebral bleeding. The mortality rate due to major bleeding was not different between patients being treated with warfarin or direct oral anticoagulants. Major bleeding while on oral anticoagulant therapy leads to considerable hospital stays and short-term mortality.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Hospital Mortality; Humans; Intracranial Hemorrhages; Length of Stay; Male; Middle Aged; Prospective Studies; Risk Factors; United Kingdom; Warfarin

The risks of intracranial haemorrhage (ICH) associated with antithrombotic drugs outside clinical trials are gaining increased attention. The aim of this nationwide study was to investigate the risk of ICH requiring hospital admission in users of antithrombotic drugs.. Data from the Norwegian Patient Registry and Norwegian Prescription Database were linked on an individual level. The primary outcome was incidence rates of ICH associated with use of antithrombotic drugs. Secondary endpoints were risk of ICH and fatal outcome following ICH assessed by Cox models. Among 3,131,270 individuals ≥18 years old observed from 2008 through 2014, there were 729,818 users of antithrombotic medications and 22,111 ICH hospitalizations. Annual crude ICH rates per 100 person-years were 0.076 (95% CI, 0.075-0.077) in non-users and 0.30 (95% CI, 0.30-0.31) in users of antithrombotic medication, with the highest age and sex adjusted rates observed for aspirin-dipyridamole plus clopidogrel (0.44; 95% CI, 0.19-0.69), rivaroxaban plus aspirin (0.36; 95% CI, 0.16-0.56), warfarin plus aspirin (0.34; 95% CI, 0.26-0.43), and warfarin plus aspirin and clopidogrel (0.33; 95% CI, 0.073-0.60). With no antithrombotic medication as reference, the highest adjusted hazard ratios (HR) for ICH were observed for aspirin-dypiridamole plus clopidogrel (6.29; 95% CI 3.71-10.7), warfarin plus aspirin and clopidogrel (4.38; 95% CI 2.71-7.09), rivaroxaban plus aspirin (3.82; 95% CI, 2.46-5.95), and warfarin plus aspirin (3.40; 95% CI, 2.99-3.86). All antithrombotic medication regimens were associated with an increased risk of ICH, except dabigatran monotherapy (HR 1.20; 95% CI, 0.88-1.65) and dabigatran plus aspirin (HR 1.79; 95% CI, 0.96-3.34). Fatal outcome within 90 days was more common in users (2,603 of 8,055) than non-users (3,228 of 14,056) of antithrombotic medication (32.3% vs 23.0%, p<0.001), and was associated with use of warfarin plus aspirin and clopidogrel (HR 2.89; 95% CI, 1.49-5.60), warfarin plus aspirin (HR 1.37; 95% CI, 1.11-1.68), aspirin plus clopidogrel (HR 1.30; 95% CI, 1.05-1.61), and warfarin (HR 1.19; 95% CI, 1.09-1.31). Increased one-year mortality was observed in users of antithrombotic medication following hemorrhagic stroke, subdural hemorrhage, subarachnoid hemorrhage, and traumatic ICH (all p<0.001). Limitations include those inherent to observational studies including the inability to make causal inferences, certain assumptions regarding drug exposure, and the possibility of residual confounding.. The real-world incidence rates and risks of ICH were generally higher than reported in randomized controlled trials. There is still major room for improvement in terms of antithrombotic medication safety (clinicaltrials.gov NCT02481011).

Topics: Adolescent; Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Male; Middle Aged; Norway; Pharmacoepidemiology; Risk Factors; Rivaroxaban; Thrombosis; Warfarin

There is limited information about the use of antithrombotic therapies and outcomes of Latin American (LatAm) subjects with atrial fibrillation. The global ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial compared the efficacy and safety of edoxaban versus warfarin over a median follow-up of 2.8 years.. The authors aimed to compare adjusted outcomes in Latin America versus outside Latin America and to compare outcomes stratified by anticoagulant treatment and region.. The authors analyzed clinical characteristics and outcomes, adjusted for baseline characteristics, the Human Development Index, and randomized treatment of 2,661 LatAm versus 18,444 non-Latin American subjects (nLAS).. After multivariable adjustment, LatAm subjects with atrial fibrillation had higher rates of intracranial hemorrhage and death than nLAS. Outcomes with higher-dose edoxaban versus warfarin were at least as favorable in LatAm subjects as in nLAS, with an even greater reduction in hemorrhagic stroke seen in LatAm.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hospitalization; Humans; Intracranial Hemorrhages; Latin America; Male; Myocardial Infarction; Pyridines; Stroke; Thiazoles; Warfarin

We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received ≥1 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was ≥4 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban- and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-term morbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as #NCT00412984.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Pyrazoles; Pyridones; Warfarin

In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear.. To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke.. A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis.. Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks.. The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length.. Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001).. In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy.. clinicaltrials.gov Identifier: NCT02042534.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Diffusion Magnetic Resonance Imaging; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Intracranial Hemorrhages; Magnetic Resonance Angiography; Male; Middle Aged; Republic of Korea; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial allowed patients who completed the trial receiving their assigned dabigatran 150 mg (D150) or 110 mg (D110) twice a day to continue into the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial. This permitted assessment of outcomes over a median of 4.6 and a maximum of 6.7 years, respectively.. The analysed population included only those patients who completed RE-LY on dabigatran and continued into RELY-ABLE without interruption of assigned dabigatran. Cumulative risk was expressed as Kaplan-Meier plots. Outcomes were compared using Cox proportional hazard modelling. Stroke or systemic embolization rates were 1.25 and 1.54% per year (D150 and D110, respectively); hazard ratio (HR) 0.81 [95% confidence interval (CI): 0.68-0.96] (P = 0.02). Ischaemic stroke was 1.03 (D150) and 1.29%/year (D110); HR 0.79 (95% CI: 0.66-0.95) (P = 0.01). Haemorrhagic stroke rates were 0.11 (D150) and 0.13%/year (D110); HR 0.91 (95% CI: 0.51-1.62) (P = 0.75). Rates of major haemorrhage were 3.34 (D150) and 2.76%/year (D110); HR 1.22 (95% CI: 1.08-1.37) (P = 0.0008). Intracranial haemorrhage rates were 0.32 (D150) and 0.23%/year (D110); HR 1.37 (95% CI: 0.93-2.01) (P = 0.11). Mortality was 3.43 (D150) and 3.55%/year (D110); HR 0.97 (95% CI: 0.87-1.08) (P = 0.54).. Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Stroke; Treatment Outcome; Warfarin; Young Adult

Traumatic intracranial bleeding, which is most commonly attributable to falls, is a common concern among health care professionals, who are hesitant to prescribe oral anticoagulants to older adults with atrial fibrillation.. To describe the incidence of and risk factors for traumatic intracranial bleeding in a large cohort of older adults who were newly prescribed warfarin sodium.. Retrospective cohort study at the US Department of Veterans Affairs (VA). Participants included 31 951 veterans with atrial fibrillation 75 years or older who were new referrals to VA anticoagulation clinics (for warfarin therapy) between January 1, 2002, and December 31, 2012. The dates of the core analysis were March 2014 through May 2015, and subsequent ad hoc analyses were performed through December 2015. Patients with comorbid conditions requiring warfarin were excluded.. The primary outcome was hospitalization for traumatic intracranial bleeding. Secondary outcomes included hospitalization for any intracranial bleeding or ischemic stroke. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify the incidence rates of these outcomes after warfarin initiation using VA administrative data (in-system hospitalizations) and Medicare fee-for-service claims data (out-of-system hospitalizations). Clinical characteristics, laboratory results, and pharmacy data were extracted from the VA electronic medical record. For traumatic intracranial bleeding, Cox proportional hazards regression was used to determine predictors of interest selected a priori based on prior known associations.. The study population comprised 31 951 participants. The mean (SD) patient age was 81.1 (4.1) years, and 98.1% were male. Comorbidities were common, including hypertension (82.5%), coronary artery disease (42.6%), and diabetes mellitus (33.8%). During the study period, the incidence rate of hospitalization for traumatic intracranial bleeding was 4.80 per 1000 person-years. In unadjusted models, significant predictors of traumatic intracranial bleeding included dementia, fall within the past year, anemia, depression, abnormal renal or liver function, anticonvulsant use, labile international normalized ratio, and antihypertensive use. After adjusting for potential confounders, the remaining significant predictors for traumatic intracranial bleeding were dementia (hazard ratio [HR], 1.76; 95% CI, 1.26-2.46), anemia (HR, 1.23; 95% CI, 1.00-1.52), depression (HR, 1.30; 95% CI, 1.05-1.61), anticonvulsant use (HR, 1.35; 95% CI, 1.04-1.75), and labile international normalized ratio (HR, 1.33; 95% CI, 1.04-1.72). The incidence rates of hospitalization for any intracranial bleeding and ischemic stroke were 14.58 and 13.44, respectively, per 1000 person-years.. Among patients 75 years or older with atrial fibrillation initiating warfarin therapy, the risk factors for traumatic intracranial bleeding are unique from those for ischemic stroke. The high overall rate of intracranial bleeding in our sample supports the need to more systematically evaluate the benefits and harms of warfarin therapy in older adults.

Topics: Aged; Atrial Fibrillation; Cohort Studies; Contraindications, Drug; Female; Humans; Intracranial Hemorrhages; Male; Proportional Hazards Models; Retrospective Studies; Risk Factors; Veterans; Warfarin

In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI.. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984.

Topics: Atrial Fibrillation; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Pyrazoles; Pyridones; Stroke; Thromboembolism; Treatment Outcome; Warfarin

We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs).. We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3±8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively).. More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hospital Mortality; Humans; Intracranial Hemorrhages; Japan; Male; Retrospective Studies; Vitamin K; Warfarin

The evaluation of the "net clinical benefit" allows an integrated assessment of both the anti-ischemic and the prohemorrhagic effects of non-vitamin K antagonist oral anticoagulants compared with warfarin, and—in the absence of direct comparisons—may inform clinical decisions. We estimated the net clinical benefit of non-vitamin K antagonist oral anticoagulants versus warfarin across the 4 phase III clinical trials performed in patients with atrial fibrillation.. We considered various composites of the main ischemic and hemorrhagic events, estimating the rate ratio of all treatment groups versus warfarin for each composite outcome. Because the clinical relevance of the various ischemic or hemorrhagic events is not identical, we then attributed to each of them a weight, according to its impact on death, as derived from previous studies. We evaluated a weighed net clinical benefit of each non-vitamin K antagonist oral anticoagulant compared with warfarin in the 4 trials.. The composite outcome of ischemic + hemorrhagic stroke was reduced by dabigatran 150 mg and apixaban. The composite of disabling stroke + life-threatening bleeding was reduced by all non-vitamin K antagonist oral anticoagulants. The composite of ischemic stroke + systemic embolism + myocardial infarction + hemorrhagic stroke + major bleeding was reduced by apixaban and edoxaban at both doses. By attributing weights to these events according to their impact on mortality, all non-vitamin K antagonist oral anticoagulants featured a favorable net clinical benefit compared with warfarin, albeit to a quantitatively different extent.. The choice of the proper antithrombotic treatment in patients with atrial fibrillation has to consider the net clinical benefit of each drug. However, all non-vitamin K antagonist oral anticoagulants have a better efficacy/safety profile than warfarin in patients with atrial fibrillation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Warfarin

This study was designed to compare effectiveness and safety of warfarin, direct thrombin inhibitor dabigatran, Xa factor inhibitors rivaroxaban and apixaban used to prevent stroke in 280 elderly patients in patients with age-specific non-valvular atrial fibrillation. The treatment of patients aged 65-74 and 75-80 yearsfor 2 years with dab itragan (110 mg b.i.d), apixaban (5 mg b. i. d), and rivaroxaban (20 mg once daily) prevented stroke as effectively as warfarin therapy but less frequently caused severe intracranial hemorrhage. It is concluded that these new anticoagulants can be used as alternative medication for antithrombotic therapy of elderly patients with age-specific non-valvular atrialfibrillation.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Drug Monitoring; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

 Epidemiology and clinical management of acute venous thromboembolism (VTE) are not readily available in Japan..  The Japan VTE Treatment Registry (JAVA) is a multicenter cohort study of consecutive patients with an objectively confirmed, symptomatic acute pulmonary embolism (PE), symptomatic acute deep vein thrombosis (DVT), or asymptomatic acute proximal DVT. Of the 1,076 patients enrolled with acute VTE, 68.7% presented with an isolated DVT; 17.0% had PE alone; and 14.4% had both. VTE management was characterized by a high rate of inferior vena cava filter insertion (40.6%), frequent thrombolysis (21.1%), and sub-therapeutic unfractionated heparin-based anticoagulation, followed by warfarin prescription, mostly targeting an international normalized ratio of 2.0 (range, 1.5-2.5). During a mean observation period of 252.5 days, 29 recurrent cases of VTE were documented, yielding an incidence rate of 3.9 per 100 patient-years. A total of 123 patients died during the study period, corresponding to a rate of 16.6 deaths per 100 patient-years. The incidence of major bleeding was 3.2% per patient-year, including 2 fatal hemorrhages and 7 intracranial hemorrhages..  VTE management in Japan is characterized by a highly aggressive strategy in the acute phase, in contrast to protocols that use low-level anticoagulation. The VTE recurrence rates in Japan and Western countries are similar, but mortality is higher in Japan, with significant variability depending on patient and management characteristics. 

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Japan; Male; Middle Aged; Retrospective Studies; Thrombolytic Therapy; Vena Cava Filters; Venous Thromboembolism; Warfarin

Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation.. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used.. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73).. Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

Topics: Aged; Anticoagulants; Asian People; Atrial Fibrillation; Black People; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Morpholines; Prospective Studies; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries.. There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used.. Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3-4.7; P=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03-0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06-0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19-0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13-0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year).. Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups.. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Asia; Asian People; Atrial Fibrillation; Benzimidazoles; Brain Ischemia; Dabigatran; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyridines; Stroke; Warfarin

Compared with warfarin, dabigatran is associated with less intracranial hemorrhage, but an increased risk of myocardial infarction. To explore these phenomena, we compared their effects on thrombin generation. Thrombin generation in plasma from 10 patients taking therapeutic doses of warfarin (mean INR 2.6) was compared with that in plasma containing 250 ng/mL dabigatran. Although lag times were similar when thrombin generation was induced by recalcification or with a range of tissue factor concentrations, there was a greater reduction in peak thrombin generation and endogenous thrombin potential in plasma from warfarin-treated patients than in dabigatran-containing plasma. Similar results were obtained when thrombin generation was determined in plasma samples from 18 warfarin or 36 dabigatran treated patients entered into the RE-LY trial. Warfarin suppresses thrombin generation more efficiently than dabigatran. Greater suppression of normal hemostatic mechanisms in the brain and pathological thrombosis at sites of atherosclerotic plaque disruption may explain the higher rate of intracranial bleeding and lower rate of myocardial infarction with warfarin compared with dabigatran.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Thrombin; Warfarin

Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined.. Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily).. During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001).. The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Radiography; Risk Factors; Warfarin

The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF.. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050).. J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Morpholines; Prospective Studies; Rivaroxaban; Stroke; Thiophenes; Warfarin

The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding.. ARISTOTLE was a double-blind, randomised trial that enrolled 18,201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2·0-3·0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984.. Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or ≥3, p for interaction=0·4457; or CHA(2)DS(2)VASc 1, 2, or ≥3, p for interaction=0·1210) or bleeding (HAS-BLED 0-1, 2, or ≥3, p for interaction=0·9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0·4018; CHA(2)DS(2)VASc, p for interaction=0·2059; HAS-BLED, p for interaction=0·7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0·22, 95% CI 0·10-0·48) than in those with HAS-BLED scores of 0-1 (HR 0·66, 0·39-1·12; p for interaction=0·0604).. Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2, CHA2DS2VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events.. Bristol-Myers Squibb and Pfizer.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Risk Assessment; Stroke; Treatment Outcome; Warfarin

Oral anticoagulation with warfarin is widely used to treat venous and arterial thromboembolic disease (Ansell et al. Chest 133(6 suppl):160S-198S, 2008). Its administration is associated with a risk of intracranial hemorrhage (ICH), a devastating complication which usually results in death or severe disability (Fang et al. Am J Med,120(8):700-705, 2007; Rosand et al. Arch Intern Med, 164(8):880-884, 2004). The international normalized ratio (INR) is one of the factors which can help determine the risk of ICH in a given individual (Singer et al. Circ Cardiovasc Qual Outcomes, 2(4):297-304, 2009). Using the DoseResponse(®) patient database at our institution, we carried a retrospective nested matched case-control study to identify patient characteristics associated with the occurrence of ICH. The database was queried for the years 2004-2009. Each case was matched by month to four control patients having a routine INR determination for the monitoring of chronic anticoagulation. The following characteristics were captured: bleeding type, INR, age, sex, blood pressure, hemoglobin, creatinine, presence or history of pertinent comorbid conditions, intake of antiplatelet agents (aspirin or thienopyridine) and indication for anticoagulation. The relationship between those risk factors and the odds ratio of ICH was determined with conditional logistic regression. Fifty cases of ICH were retrieved. When correcting for pertinent variables, the odds ratio of ICH increased significantly for higher INR values, with a quadratic relationship noted in the model. Increasing mean blood pressure seemed to be associated with a higher risk of ICH, also in an exponential manner. Rising hemoglobin values on the other hand seemed to have a protective effect against such events. About 50% of cases of ICH occurred in or below the therapeutic INR range. The intake of antiplatelet agent was found to be associated with ICH in univariate analysis only. The INR is an important predictor for the incidence of ICH, but in this study an elevated measurement was found in only half of cases. Mean blood pressure appears to be another important determinant of the risk of ICH in the anticoagulated patient population.

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Blood Pressure; Case-Control Studies; Databases, Factual; Female; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Male; Models, Cardiovascular; Platelet Aggregation Inhibitors; Pyridines; Risk; Sex Factors; Warfarin

The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients.. Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA.. Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Embolism; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyridines; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

Intraparenchymal hemorrhage (IPH) volume is a powerful predictor of 30-day mortality. Warfarin-related intracranial hemorrhage (ICH) has a higher mortality than ICH without anticoagulation, possibly due to continued growth after 24 h, larger average size, and extension to extraparenchymal compartments. We compared 2 methods of measuring ICH volume in patients with warfarin-related ICH.. ICH volume was estimated using the ABC/2 method and a computer-assisted method (Analyze 6.0 software) applied to the initial head computed tomographic scans in a consecutive series of 8 patients with warfarin-related ICH. The 2 methods were compared for relative and absolute differences in estimated hematoma volumes.. The ABC/2 method underestimated hematoma volume in 4 of 5 patients with IPH, inaccurately calculated intraventricular hemorrhage volume in 2 patients (overestimated by 9%, underestimated by 23%), and underestimated a complex subdural hematoma in 1 patient by 24% despite use of the Gebel modification. The mean percentage difference between the Analyze and ABC/2 methods was 24% in ellipsoid hemorrhages and 28% in nonellipsoid hemorrhages (P = 0.77). The mean of the absolute difference between the 2 methods was 6.7 cm3 in ellipsoid hemorrhages and 38.0 cm3 in nonellipsoid hemorrhages (P = 0.18).. The ABC/2 method accurately and quickly estimates smaller, ellipsoid intraparenchymal hematomas but is inaccurate for larger, complex-shaped warfarin-related intraparenchymal, intraventricular, and subdural hematomas. Warfarin-related ICH mortality may be underestimated by the ABC/2 method because of larger, complex-shaped, and multicompartmental hematomas.

Topics: Algorithms; Anticoagulants; Cohort Studies; Humans; Image Processing, Computer-Assisted; Intracranial Hemorrhages; Predictive Value of Tests; Reproducibility of Results; Tomography, X-Ray Computed; Warfarin

To determine the strength of oral anticoagulation therapy in atrial fibrillation that provides the best balance between the prevention of thromboembolism and the occurrence of bleeding complications.. We studied 435 patients with atrial fibrillation who were hospitalized from 2000 to 2002 and given warfarin for prevention of thromboembolism. INR-specified rates for both ischemic and major hemorrhagic events were analyzed and the optimal levels of anticoagulation in atrial fibrillation patients determined.. The average dose of warfarin was (2.77 +/- 0.83) mg and the median duration of anticoagulation is 7 months (from 1 month to 3 years). In total, there were 31 confirmed bleeding events, with major hemorrhage occurring in 5 patients. Age of the patients in the hemorrhage group is not significantly higher than that in control group (65.09 +/- 9.99 vs 62.01 +/- 12.19, P = 0.259). Chronic heart failure or hypertension increased the risk of bleeding during warfarin therapy. Multivariate analysis showed that INR >or= 3.0 is an independent risk factor for hemorrhage (OR = 3.7435, 95% CI 1.2819 - 8.9838). The risk of stroke or thromboembolism rose steeply with INR below 1.5.. To achieve optimal levels of anticoagulation with the lowest risk in patients with atrial fibrillation, values of INR below 1.5 and above 3.0 should be avoided.

Topics: Adult; Anticoagulants; Atrial Fibrillation; China; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Risk Factors; Treatment Outcome; Warfarin

Anticoagulation-treated patients presenting with intracranial hemorrhage, including subdural hematoma, epidural hematoma, subarachnoid hemorrhage, and intracerebral hemorrhage, require urgent correction of their coagulopathy to prevent worsening hemorrhage and to facilitate surgical intervention when necessary. In this study, we compared the use of fresh frozen plasma (FFP) with that of Factor IX complex concentrate (FIXCC) to achieve rapid correction of warfarin anticoagulation.. Patients admitted to a tertiary care center with computed tomography-proven intracranial hemorrhage and a prothrombin time of more than 17 seconds were considered for inclusion in the study protocol. Complete data sets were obtained for eight patients randomized to treatment with FFP and five patients randomized to treatment with FFP supplemented with FIXCC. The prothrombin time and International Normalized Ratio were measured every 2 hours for 14 hours. Correction of anticoagulation was defined as an International Normalized Ratio of < or =1.3.. A difference in repeated International Normalized Ratio measurements during the first 6 hours of correction was observed between the FIXCC and FFP groups (P < 0.03). The rate of correction was greater (P < 0.01) and the time to correction was shorter (P < 0.01) for the FIXCC-treated group. No difference in neurological outcomes was detected between groups, but a higher complication rate was observed for the FFP-treated group.. The use of FIXCC accelerated correction of warfarin-related anticoagulation in the presence of intracranial hemorrhage.

Topics: Factor IX; Glasgow Coma Scale; Humans; Infusions, Intravenous; International Normalized Ratio; Intracranial Hemorrhages; Plasma; Treatment Outcome; Warfarin

We assessed the cumulative incidence of recurrent stroke, major bleeding and all-cause mortality associated with restarting antithrombotic treatment, in patients experiencing an anticoagulation-related event (stroke or major bleeding), occurred during anticoagulation therapy for AF.. We performed a retrospective population-based analysis on linked claims data of patients resident in the Veneto Region, treated with DOACs for AF and discharged (2013-2020) from the hospital for stroke, intracranial haemorrhage (ICH), and major bleeding. To adjust for competing risk of death and reduce confounding, we started the follow up after a 120-days blanking period, counting events in patients resuming oral anticoagulation versus those that did not. Risks of all-cause mortality, ischemic stroke (IS)intracranial haemorrhage (ICH), and other major bleeding events (MB) were estimated with multivariable Cox proportional hazard models and propensity score to adjust for differences in baseline characteristics. Overall, 1029 patients (mean age 77 years) were included in the final cohort: 23% experienced an IS, 18% an ICH, and 59% MB. Of these, 77% resumed anticoagulation. The cumulative incidence of events was significantly lower in patients resuming therapy. In the multivariable analysis considering age, sex and propensity score as covariates, resumption of anticoagulation significantly reduced the risk of a cumulative event (HR 0.45, 95%CI 0.35-0.57, p < 0.01). Stratifying for the index event, among patients with IS (92% resumed therapy), we observed a risk reduction of 81%; in patients with ICH (64% resumed therapy), we observed a risk reduction of 64% and for patients with MB (76% resuming therapy), we observed a risk reduction of 49%.. In patients with AF who experienced an anticoagulation-related event, resuming oral anticoagulation was associated with better outcomes for all-cause mortality and subsequent events as compared with patients who did not resume treatment.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Retrospective Studies; Stroke; Warfarin

Background We aimed to determine the effect of integrating Atrial Fibrillation Better Care pathway compliance in relation to achievement of systolic blood pressure (SBP) targets and good control of time in therapeutic range (TTR) on clinical outcomes in patients with atrial fibrillation. Methods and Results We prospectively enrolled patients with nonvalvular atrial fibrillation  from 27 hospitals in Thailand. All clinical outcomes were recorded. Main outcomes were the composite of all-cause death or ischemic stroke/systemic embolism (SSE), as well as secondary outcomes of all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure. An SBP of 120 to 140 mm Hg was considered good blood pressure control. Target TTR was a TTR ≥65%. A total of 3405 patients were studied (mean age 67.8 years, 41.8% female). Full ABC pathway compliance was evident in 42.7%. For blood pressure control, 41.9% had SBP within target, whereas 35.9% of those on warfarin had TTR within target. The incidence rates of all-cause death/SSE, all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure were 5.29, 4.21, 1.51, 2.25, 0.78, and 2.84 per 100 person-years respectively. Adjusted hazard ratios and 95% CI of Atrial Fibrillation Better Care pathway compliance for all-cause death/SSE, all-cause death, and heart failure were 0.76 (0.62-0.94), 0.79 (0.62-0.99), and 0.69 (0.51-0.94), respectively, compared with noncompliance. Patients with Atrial Fibrillation Better Care compliance and SBP within target had a better outcome or TTR within target had better outcomes. Conclusions In COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Level in Patients With Non-Valvular Atrial Fibrillation in Thailand), a multicenter nationwide prospective cohort of patients with atrial fibrillation, achieving SBP within target and TTR ≥ 65% has added value to Atrial Fibrillation Better Care pathway compliance in the reduction of adverse clinical outcomes in patients with atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Pressure; Critical Pathways; Embolism; Female; Heart Failure; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

Liu S, McLeod SL, Atzema CL, et al.

Topics: Adult; Aged; Anticoagulants; Craniocerebral Trauma; Humans; Intracranial Hemorrhages; Retrospective Studies; Warfarin

Nationally, the volume of geriatric falls with intracranial hemorrhage is increasing. Our institution began observing patients with intracranial hemorrhage, Glasgow Coma Scale of 14 or greater, and no midline shift or intraventricular hemorrhage with hourly neurologic examinations outside of the ICU in a high observation trauma (HOT) protocol. We first excluded patients on anticoagulants or antiplatelets (HOT I), then included antiplatelets and warfarin (HOT II), and finally, included direct oral anticoagulants (HOT III). Our hypothesis is that HOT protocol safely reduces ICU use and creates cost savings in this patient population.. Our institutional trauma registry was retrospectively queried for all patients on HOT protocol. Patients were stratified based on date of admission (HOT I [2008-2014], HOT II [2015-2018], and HOT III [2019-2021]), and were compared for demographics, anticoagulant use, injury characteristics, lengths of stay, incidence of neurointervention, and mortality.. During the study period, 2,343 patients were admitted: 939 stratified to HOT I, 794 to HOT II, and 610 to HOT III. Of these patients, 331 (35%), 554 (70%), and 495 (81%) were admitted to the floor under HOT protocol, respectively. HOT protocol patients required neurointervention in 3.0%, 0.5%, and 0.4% of cases in HOT I, II, and III, respectively. Mortality among HOT protocol patients was found to be 0.6% in HOT I, 0.9% in HOT II, and 0.2% in the HOT III cohort (p = 0.33).. Throughout the study period ICU use decreased without an increase in neurosurgical intervention or mortality, indicating the efficacy of the HOT selection criteria in identifying appropriate candidates for stepdown admission and HOT protocol.

Topics: Aged; Anticoagulants; Brain Injuries, Traumatic; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Retrospective Studies; Warfarin

Background Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first-ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause-specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25-1.48], 1.63 [95% CI, 1.43-1.86], 1.32 [95% CI, 1.26-1.38], 0.96 [95% CI, 0.78-1.17], and 1.11 [95% CI, 0.99-1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. Conclusions AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Stroke; Warfarin

Elderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of intracranial hemorrhage (ICH) and its subtypes, as well as ischemic stroke, in patients taking direct oral anticoagulants (DOACs) compared with warfarin in a real-world setting. We also determined the baseline characteristics associated with both ICH and ischemic stroke.. Patients aged ⩾ 75 years with documented NVAF enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were evaluated. The co-primary endpoints were the incidence of ischemic stroke and ICH. Secondary endpoints included subtypes of ICH.. Of 32,275 patients (13,793 women; median age, 81.0 years) analyzed, 21,585 (66.9%) were taking DOACs and 8233 (25.5%) were taking warfarin. During the median 1.88-year follow-up, 743 patients (1.24/100 person-years) developed ischemic stroke and 453 (0.75/100 person-years) developed ICH (intracerebral hemorrhage, 189; subarachnoid hemorrhage, 72; subdural/epidural hemorrhage, 190; unknown subtype, 2). The incidence of ischemic stroke (adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.70-0.97), ICH (aHR 0.68, 95% CI 0.55-0.83), and subdural/epidural hemorrhage (aHR 0.53, 95% CI 0.39-0.72) was lower in DOAC users versus warfarin users. The incidence of fatal ICH and fatal subarachnoid hemorrhage was also lower in DOAC users versus warfarin users. Several baseline characteristics other than anticoagulants were also associated with the incidence of the endpoints. Of these, history of cerebrovascular disease (aHR 2.39, 95% CI 2.05-2.78), persistent NVAF, (aHR 1.90, 95% CI 1.53-2.36), and long-standing persistent/permanent NVAF (aHR 1.92, 95% CI 1.60-2.30) was strongly associated with ischemic stroke; severe hepatic disease (aHR 2.67, 95% CI 1.46-4.88) was strongly associated with overall ICH; and history of fall within 1 year was strongly associated with both overall ICH (aHR 2.29, 95% CI 1.76-2.97) and subdural/epidural hemorrhage (aHR 2.90, 95% CI 1.99-4.23).. Patients aged ⩾ 75 years with NVAF taking DOACs had lower risks of ischemic stroke, ICH, and subdural/epidural hemorrhage than those taking warfarin. Fall was strongly associated with the risks of intracranial and subdural/epidural hemorrhage.. The individual de-identified participant data and study protocol will be shared for up to 36 months after the publication of the article. Access criteria for data sharing (including requests) will be decided on by a committee led by Daiichi Sankyo. To gain access, those requesting data access will need to sign a data access agreement. Requests should be directed to yamt-tky@umin.ac.jp.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Female; Humans; Intracranial Hemorrhages; Ischemic Stroke; Prospective Studies; Registries; Stroke; Subarachnoid Hemorrhage; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Stroke; Warfarin

The purpose of this study is to assess efficacy of 4-factor prothrombin complex concentrates (4F-PCC) for direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) as compared to its use in warfarin-associated ICH. A retrospective cohort study was performed to compare the efficacy of 4F-PCC for reversal of apixaban and rivaroxaban versus warfarin for ICH at Cooper University Health Care from January 2015 to December 2019. Patients included were ≥ 18 years of age who developed an ICH while on apixaban, rivaroxaban, or warfarin. The primary outcome was to compare the percentage of patients with Excellent or Good hemostatic efficacy after 4F-PCC administration. Secondary outcomes were to describe functional outcomes at discharge, in-hospital mortality, and thrombotic complications after 4F-PCC administration. A total of 159 patients were included; 115 patients received warfarin and 44 patients received a DOAC (apixaban, n = 22; rivaroxaban, n = 22). 70 patients were evaluable for the primary endpoint. Thirty-four (66.7%) patients in the warfarin group versus 14 (73.7%) patients in the DOAC group were determined to have excellent or good hemostatic efficacy (p = 0.57). In-hospital mortality (30.4% vs. 40.9%, p = 0.21) and thrombotic complications (9.6% vs. 11.4%, p = 0.67) were comparable between the warfarin vs. DOAC groups, respectively. This small, retrospective study found no difference in patients with excellent/good hemostatic efficacy after reversal with 4F-PCC for DOAC-associated ICH compared to warfarin-associated ICH. This study is limited by its retrospective nature and sample size. Larger, prospective studies are needed to further determine the efficacy of 4F-PCC in reversing DOAC-associated ICH.

Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Hemostatics; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Warfarin

The aim of this paper is to assess the acute haemorrhage rate in patients who had CT head investigation out-of-hours with and without trauma and compare the rates of haemorrhage between warfarin and DOACs, at a busy teritary teaching hospital.. All CT heads performed between January 2008 and December 2019 were identified from the radiology information system (RIS) at Sheffield Teaching Hospitals (STH), with the requesting information being available from January 2015. The clinical information was assessed for the mention of trauma or anticoagulation, and the reports were categorised into acute and non-acute findings.. Between 2008 and 2019 the number of scans increased by 63%, with scans performed out of hours increasing by 278%. Between 2015 and 2019, the incidence of acute ICH was similar over the 5-year period, averaging at 6.9% and ranging from 6.1 to 7.6%. The rate of detection of acute haemorrhage following trauma was greater in those not anticoagulated (6.8%), compared with patients on anticoagulants such as warfarin (5.2%) or DOACs (2.8%).. Over 12 years, there has been a significant increase in the number of CT heads performed at STH. The rate of ICH has remained steady over the last 5 years indicating a justified increase in imaging demand. However, the incidence of ICH in patients prescribed DOACs is lower than the general population and those on warfarin.. This finding in a large centre should prompt discussion of the risk of bleeding with DOACs in relation to CT head imaging guidelines.

Topics: Adolescent; Adult; After-Hours Care; Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Tomography, X-Ray Computed; Trauma Centers; United Kingdom; Warfarin; Young Adult

 Intracranial hemorrhage (ICH) is one of the major devastating complications of anticoagulation. Matrix metalloproteinase (MMP) inhibition has been proposed as a novel pharmacological approach for ICH treatment..  We evaluated the effects of CM-352 (MMP-fibrinolysis inhibitor) in an experimental ICH model associated with oral anticoagulants as compared with clinically used prothrombin complex concentrate (PCC)..  ICH was induced by collagenase injection into the striatum of wild type (C57BL/6J) anticoagulated mice (warfarin or rivaroxaban) and.  Only PCC reduced hemorrhage volume and improved functional outcome in warfarin-ICH, but both PCC and CM-352 treatments diminished hemorrhage volume (46%,.  CM-352 treatment, by diminishing MMPs and rivaroxaban-associated fibrinolytic effects, might be a novel antihemorrhagic strategy for rivaroxaban-associated ICH.

Topics: Animals; Anticoagulants; Benzamides; Blood Coagulation Factors; Cerebral Hemorrhage; Disease Models, Animal; Hydroxamic Acids; Interleukin-6; Intracranial Hemorrhages; Matrix Metalloproteinase 10; Mice; Mice, Inbred C57BL; Plasminogen Activator Inhibitor 1; Rivaroxaban; Warfarin

Few studies assessed the association between major adverse cardiovascular events and adherence to warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). Therefore, we aimed to evaluate the effects of adherence to oral anticoagulants (OACs) in patients with AF using claims data (July 2014-April 2019). Using the initial 3-month medication possession rate (MPR), patients were categorized into adherent (MPR ≥ 0.8) or non-adherent (MPR < 0.8) groups. Propensity score matching of non-adherent group to adherent group was conducted for warfarin (1:1) and DOAC (1:3), respectively. Incidence of ischemic stroke, myocardial infarction (MI), intracranial hemorrhage, and all-cause death was assessed in the matched cohort (67,147 patients). The hazard ratio (HR) for adherence to OAC was estimated using the Cox proportional hazard model with adjusting covariate including age and sex. The risk for ischemic stroke, MI, and all-cause death was lower in the DOAC adherent group than in the DOAC non-adherent group (HR: 0.78; 95% confidence intervals: 0.73-0.84; 0.75, 0.60-0.94; 0.54, 0.51-0.57, respectively). Adherence to OAC was not associated with the risk of intracranial hemorrhage (1.01, 0.85-1.20). Commitment programs to improve adherence in patients with AF could maximize drug effectiveness and safety.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Ischemic Stroke; Myocardial Infarction; Retrospective Studies; Stroke; Warfarin

Background To investigate the effectiveness and safety of withholding or restarting antithrombotic agents, and different antithrombotic therapies among patients with atrial fibrillation post-intracranial hemorrhage. Methods and Results This is a nationwide retrospective cohort study involving patients with atrial fibrillation receiving antithrombotic therapies who subsequently developed intracranial hemorrhage between January 1, 2011 and December 31, 2017. The risk of ischemic stroke (IS), recurrent intracerebral hemorrhage (ICH), and all-cause mortality were investigated between patients receiving no treatment versus patients reinitiating oral anticoagulants (OACs) or antiplatelet agents, and warfarin versus non-vitamin K antagonist OACs. We applied inverse probability of treatment weighting to balance the baseline characteristics and Cox proportional hazards model to estimate the hazard ratios (HRs) of different outcomes of interest. Compared with no treatment, OACs reduced the risk of IS (HR, 0.61; 0.42-0.89), without increase in the risk of ICH (1.15, 0.66-2.02); antiplatelet agent users showed a similar risk of IS (1.13, 0.81-1.56) and increased risk of ICH (1.81, 1.07-3.04). Use of OACs or antiplatelet agents did not reduce the risk of all-cause mortality (0.85, 0.72-1.01; and 0.88, 0.75-1.03, respectively). Compared with warfarin, non-vitamin K antagonist OAC users showed a similar risk of IS (0.92, 0.50-1.70), non-significantly reduced risk of ICH (0.53, 0.22-1.30), and significantly reduced all-cause mortality (0.60, 0.43-0.84). Conclusions OACs are recommended in patients with atrial fibrillation and intracranial hemorrhage because they reduced the risk of IS with no increase in the risk of subsequent ICH. Non-vitamin K antagonist OACs are recommended over warfarin owing to their survival benefits.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Retrospective Studies; Stroke; Warfarin

In Denmark, physicians are legally obliged to report serious adverse drug reactions (ADRs), such as intracranial hemorrhage (ICH) following anticoagulant (AC) treatment, to the Danish Medicines Agency. We were therefore puzzled to discover a high number of reports concerning ICHs following treatment with the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin. This was surprising, as all DOACs have been found to be associated with a lower risk of ICH compared with warfarin in phase III randomized controlled trials.. The primary aim of the study was to estimate the level of underreporting of ICH as an ADR following treatment with warfarin, dabigatran, rivaroxaban, and apixaban.. This observational study covered a 5-year period (2014-2018). Using nationwide registries held by the Danish Health Data Authority, the number of users, exposure time in person-years, and related ICH events for each of the study drugs were estimated. Data on ADR-ICH reports were extracted from the interactive ADR overviews held by the Danish Medicines Agency.. From 2014 to 2018, 97.0% of the identified warfarin-related ICH events were not reported as ADRs. For the DOACs, the level of underreporting ranged from 88.8 to 90.8%.. We found a heavy and differentiated level of underreporting of ICH as an ADR following treatment with the four study drugs.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Denmark; Drug-Related Side Effects and Adverse Reactions; Humans; Intracranial Hemorrhages; Pyridones; Rivaroxaban; Warfarin

In trauma patients using warfarin, current guidelines recommend computed tomography of the brain (CTH), 24-hour observation, and repeat CTH to monitor for stability. Despite growing evidence of uncommon delayed hemorrhage, this remains standard practice even in mild traumatic brain injury without intracranial hemorrhage (ICH). Our study sought to determine the incidence and outcomes of delayed ICH (DICH) in trauma patients on supra-therapeutic warfarin without initial ICH.. A retrospective, single institutional study was performed of all adult trauma patients (>18 years old) who presented on prehospital warfarin with an international normalized ratio (INR) >3 and initial CTH that did not demonstrate ICH. Each of these patients underwent subsequent CTH within 24 hours and any DICH was identified. Those who demonstrated DICH were further examined to identify potential risk factors and outcomes such as need for further imaging or surgical intervention. Analyses were performed using Fisher's exact tests and Student's t-tests.. 225 patients were identified from January 2015 to April 2021 that met inclusion criteria. Of those identified, only 3 (1.33%) were found to develop any DICH on routine repeat CTH. Identified characteristics did not reach statistical significance due to the low number of DICH. None of the patients with DICH went on to require intervention.. In patients with identified traumatic injury on supra-therapeutic warfarin, an initial CTH without identified ICH alone is an adequate survey. DICH in these patients is uncommon and routine reimaging within 24 hours is unlikely to change clinical management in patients with intact neurologic status.

Topics: Adolescent; Adult; Anticoagulants; Craniocerebral Trauma; Humans; Intracranial Hemorrhages; Retrospective Studies; Warfarin

Hemoglobin levels and platelet counts have been associated with adverse clinical outcomes in patients with cardiovascular conditions. We aimed to assess the impact of oral anticoagulant use for patients with atrial fibrillation and concomitant anemia or thrombocytopenia.. We used medical data from a multicenter health care system in Taiwan including 37,074 patients with atrial fibrillation. Patients were categorized into 3 groups based on hemoglobin and platelet levels: Group 1 (hemoglobin >10g/dL and platelet>100 K/µL; n = 29,147), Group 2 (hemoglobin<10 g/dL or platelet<100 K/µL; n = 7078), and Group 3 (hemoglobin <10 g/dL and platelet <100 K/µL; n = 849). Patients in each category were further stratified as 3 groups according to their stroke prevention strategies: no oral anticoagulant use (non-OAC), warfarin, or nonvitamin K antagonist oral anticoagulants (NOACs).. A higher hemoglobin or platelet level was associated with a higher risk of ischemic stroke/systemic embolism but lower risks of intracranial hemorrhage and major bleeding. The composite risks of ischemic stroke/systemic embolism, intracranial hemorrhage and major bleeding were higher in Group 3 or Group 2, compared with Group 1 (6.79% a year vs 6.41% year vs 4.13% year). Compared to non-OACs, warfarin was not associated with a lower composite risk in the 3 groups. NOACs were associated with a lower composite risk in Group 1 (adjusted hazard ratio:0.68, [95% confidence interval:0.60-0.76]) and Group 2 (adjusted hazard ratio:0.73, [95% confidence interval:0.53-0.99]) but was nonsignificant in Group 3.. Patients with atrial fibrillation with anemia or thrombocytopenia were a high-risk population. Compared with no OAC use, NOACs were associated with better clinical outcomes for patients with atrial fibrillation and advanced anemia (hemoglobin <10g/dL) or thrombocytopenia (platelet <100 K/µL) but not for those with both conditions.

Topics: Administration, Oral; Anemia; Anticoagulants; Atrial Fibrillation; Embolism; Hemoglobins; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Risk Factors; Stroke; Thrombocytopenia; Warfarin

The objective of this study was to evaluate clinical outcomes associated with time to administration and dose of four-factor prothrombin complex concentrate (4F-PCC) in patients with ICH on warfarin.. This was a single-center retrospective analysis of patients with ICH on warfarin who received 4F-PCC.. The site of the study was a large, Level I trauma, academic medical center with a dedicated neurologic intensive care unit and an emergency department (ED) that has approximately 72,000 visits annually.. Patients were included if they were ≥18 years of age, diagnosed with ICH, had an INR >1 due to warfarin use, and received both 4F-PCC and IV vitamin K for anticoagulation reversal. Exclusion criteria included patients who were less than 18 years of age, were not currently taking warfarin, had a bleeding site other than ICH, were pregnant or incarcerated, had an inadequate medical record, had a left ventricular assist device, had known liver disease with Child-Pugh Class C, received anticoagulation with heparin therapy within 24 h of anticoagulation reversal, or did not receive vitamin K within 24 h of hospital admission.. Our primary outcome was a composite of hematoma expansion or death due to neurologic injury. Treatment groups were defined as receipt of 4F-PCC within 0-30, 31-60, 61-90, 91-120 min, or greater than 120 min. Hematoma expansion was defined as any increase in hematoma size as assessed by a radiologist via standard 6-h CT. Death due to neurologic injury was defined as death prior to a repeat CT being performed or documentation of a neurologic cause of death. Adequate INR reversal (INR ≤1.3 on repeat INR) vs. inadequate INR reversal and weight-based vs. fixed-dose 4F-PCC were also assessed.. A total of 94 patients met the inclusion criteria. Forty-one patients (43.6%) met the composite endpoint, including 60% of the 31-60 min group, 47.6% of the 61-90 min group, 71.4% of the 91-120 min group, and 30.6% of the >120-min group. A significant difference in primary outcome occurred between the 91-120 min and >120-min groups (71.4% vs. 30.6%; p= 0.005), but this difference was not observed when accounting for disparities in Glasgow Coma Scale (GCS). Patients with adequate INR reversal were less likely to meet the primary endpoint than those with inadequate INR reversal (28.1% vs. 58.6%; p= 0.0059). There was less failure of anticoagulation reversal with weight-based dosing compared with fixed dosing (24.2% vs. 65.0%; p< 0.001).. No difference in clinical outcomes among 4F-PCC dosing strategies or time windows to administration was observed in patients with GCS <15. Rates of repeat INR ≤1.3 were higher with weight-based dosing, suggesting investigation of populations in which fixed dosing may be inappropriate is warranted.

Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Hematoma; Humans; International Normalized Ratio; Intracranial Hemorrhages; Retrospective Studies; Vitamin K; Warfarin

Four-factor prothrombin complex concentrate 4F-PCC is the standard of care for warfarin reversal in patients with major bleed or requiring urgent surgery. Although the 4F-PCC dose is weight and international normalized ratio (INR) based, for practical purposes, a fixed-dose approach has been explored, especially for rapid reversal. We report our experience using two different fixed-dose 4F-PCC for warfarin reversal in patients presenting with intracranial hemorrhage (ICH).. We completed a retrospective chart review comparing high (4000 units) versus low (2000 units) dose 4F-PCC by evaluating patient characteristics, laboratory data, and pre-and post-4F-PCC brain imaging.. There was no significant difference between patient characteristics or INR correction (≤1.5) between the two groups. Eighty percent (12/15) of patients who received the low dose 4F-PCC had either improved or stable brain imaging as compared to 88% (14/16) of patients who received the high dose PCC. When the eight patients (4 from each arm of the study) who required neurosurgery were excluded, only two patients in each arm had worse imaging after 4F-PCC.. There was no significant difference between the INR correction and the brain imaging changes in patients with an ICH who received either the high or the low fixed-dose 4F-PCC for warfarin reversal.

Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Humans; International Normalized Ratio; Intracranial Hemorrhages; Retrospective Studies; Warfarin

To investigate effects of appropriately and inappropriately dosed apixaban/rivaroxaban versus warfarin on effectiveness and safety outcomes in patients with non-valvular atrial fibrillation (NVAF).. Cohort study with nested case-control analyses using primary care electronic health records (IQVIA Medical Research Data UK database).. UK primary care.. Patients aged ≥18 years with NVAF newly prescribed apixaban (N=14 701), rivaroxaban (N=14 288) or warfarin (N=16 175) between 1 January 2012 and 30 June 2018, and followed up to 31 December 2018.. Incident cases of ischaemic stroke/systemic embolism (IS/SE) and intracranial bleeding (ICB). Cases were matched to controls on age, sex and OAC naïve status. Using logistic regression, adjusted ORs with 95% CIs were calculated for the outcomes comparing apixaban/rivaroxaban use (appropriate or inappropriate dosing based on the product label criteria) and warfarin.. For IS/SE, ORs (95% CIs) for apixaban versus warfarin were 1.19 (0.92-1.52) for appropriate dose and 1.01 (0.67-1.51) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 1.07 (0.83-1.37) for appropriate dose and 1.21 (0.78-1.88) for inappropriate dose. For ICB, ORs (95% CIs) for apixaban versus warfarin were 0.67 (0.44-1.00) for appropriate dose and 0.45 (0.21-0.95) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 0.81 (0.55-1.20) for appropriate dose and 1.14 (0.56-2.31) for inappropriate dose.. Dosing appropriateness in NVAF was not associated with a significant difference in IS/SE risk or increase in ICB risk versus warfarin. These findings may reflect residual confounding and biases that were difficult to control, as also seen in other observational studies. They should, therefore, be interpreted with caution, and prescribers should adhere to the dosing instructions in the respective Summary of Product Characteristics. Further studies on this topic from real-world populations are needed.

Topics: Adolescent; Adult; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Cohort Studies; Embolism; Humans; Intracranial Hemorrhages; Ischemic Stroke; Primary Health Care; Pyrazoles; Pyridones; Rivaroxaban; United Kingdom; Warfarin

Elderly patients on oral anticoagulation are commonly seen in emergency departments (EDs). Oral anticoagulation, particularly warfarin, is associated with an increased risk of intracranial hemorrhage after head trauma. Data on delayed bleeds in anticoagulated patients are limited. The objective of this study was to examine risk of delayed intracranial hemorrhage in patients presenting to the ED with a head injury anticoagulated with warfarin or a direct oral anticoagulant, compared to patients not anticoagulated.. Cohort study using administrative data from Ontario of patients ≥ 65 years presenting to the ED with a complaint of head injury between 2016 and 2018. The primary outcome was delayed intracranial hemorrhage, defined as a new ICD-10 code for intracranial hemorrhage within 90 days of the initial ED visit for a head injury where no intracranial hemorrhage was diagnosed. The main exposure variable was oral anticoagulation use, which was a three-level variable (warfarin, direct oral anticoagulants, or no oral anticoagulation). We used multivariable logistic regression to determine the odds of delayed intracranial hemorrhage based on anticoagulation status.. 69,321 patients were included: 58,233 (84.0%) had not been prescribed oral anticoagulation, 3081 (4.4%) had a warfarin prescription, and 8007 (11.6%) had a direct oral anticoagulant prescription. Overall, 718 (1.0%) patients had a delayed intracranial hemorrhage within 90 days of ED visit for head injury. Among patients not anticoagulated, 586 (1.0%) had a delayed intracranial hemorrhage, 54 (1.8%) patients on warfarin, and 78 (1.0%) patients on a direct oral anticoagulant had a delayed intracranial hemorrhage. There was an increased odds of delayed intracranial hemorrhage with warfarin use compared with no anticoagulation (OR 1.5, 95% CI 1.1-2.1). There was no association between delayed intracranial hemorrhage and direct oral anticoagulant use compared to no anticoagulation (OR 0.9, 95% CI 0.6-1.1).. There was an increased odds of delayed intracranial hemorrhage within 90 days in older ED head injured patients prescribed warfarin compared to patients not on anticoagulation. direct oral anticoagulant use was not associated with increased risk of delayed intracranial hemorrhage.. RéSUMé: INTRODUCTION: Les patients âgés sous anticoagulation orale sont fréquemment accueillis dans les services d'urgence. L'anticoagulation orale, en particulier la warfarine, est associée à un risque accru d'hémorragie intracrânienne après un traumatisme crânien. Les données sur les saignements retardés chez les patients anticoagulés sont limitées. L'objectif de cette étude était d'examiner le risque d'hémorragie intracrânienne tardive chez les patients se présentant aux urgences avec un traumatisme crânien et anticoagulés avec de la warfarine ou un anticoagulant oral direct, par rapport aux patients non anticoagulés. MéTHODES: Étude de cohorte utilisant les données administratives de l'Ontario des patients ≥ 65 ans se présentant aux urgences avec une plainte de traumatisme crânien entre 2016 et 2018. L'issue primaire était l'hémorragie intracrânienne tardive, définie comme un nouveau code CIM-10 pour une hémorragie intracrânienne dans les 90 jours suivant la visite initiale aux urgences où aucune hémorragie intracrânienne n'a été diagnostiquée. La principale variable d'exposition était le recours à l'anticoagulation orale, qui était une variable à trois niveaux (warfarine, anticoagulants oraux directs ou pas d'anticoagulation orale). Nous avons utilisé une régression logistique multivariable pour déterminer les chances d'hémorragie intracrânienne tardive en fonction du statut d'anticoagulation. RéSULTATS: 69 321 patients ont été inclus : 58 233 (84,0 %) n'avaient pas reçu de prescription d'anticoagulant oral, 3 081 (4,4 %) avaient une prescription de warfarine et 8 007 (11,6 %) avaient une prescription directe d'anticoagulant oral. Dans l'ensemble, 718 (1,0 %) patients ont présenté une hémorragie intracrânienne tardive dans les 90 jours suivant leur visite aux urgences pour un traumatisme crânien. Parmi les patients non anticoagulés, 586 (1,0 %) ont eu une hémorragie intracrânienne retardée, 54 (1,8 %) patients sous warfarine et 78 (1,0 %) patients sous anticoagulant oral direct ont eu une hémorragie intracrânienne retardée. Le risque d'hémorragie intracrânienne tardive était plus élevé avec l'utilisation de la warfarine qu'en l'absence d'anticoagulation (OR : 1,5, IC 95 % : 1,1-2,1). Il n'y avait pas d'association entre l'hémorragie intracrânienne tardive et l'utilisation d'anticoagulants oraux directs par rapport à l'absence d'anticoagulation (OR : 0,9, IC 95 % : 0,6-1,1). CONCLUSIONS: Il y avait une probabilité accrue d'hémorragie intracrânienne re

Topics: Aged; Anticoagulants; Cohort Studies; Craniocerebral Trauma; Emergency Service, Hospital; Hemorrhage; Humans; Intracranial Hemorrhages; Retrospective Studies; Warfarin

Intracranial hemorrhage (ICH) after head injury is a concern among older adult patients on anticoagulation. We evaluated the risk of ICH after an emergency department visit for head injury among patients 65 years and older taking warfarin or a direct oral anticoagulant (DOAC) compared with patients not taking anticoagulants. We also evaluated risk of 30-day mortality and neurosurgical intervention among patients with ICH.. In this retrospective cohort study, we used population-based data of patients 65 years and older seen in an Ontario emergency department with a head injury. We matched patients on the propensity score to create 3 pairwise-matched cohorts based on anticoagulation status (warfarin v. DOAC, warfarin v. no anticoagulant, DOAC v. no anticoagulant). For each cohort, we calculated the relative risk of ICH at the index emergency department visit and 30-day mortality. We also calculated the hazard of neurosurgical intervention among patients with ICH.. We identified 77 834 patients with head injury, including 64 917 (83.4%) who were not on anticoagulation, 9214 (11.8%) who were on DOACs and 3703 (4.8%) who were on warfarin. Of these, 5.9% of patients had ICH at the index emergency department visit. Patients on warfarin had an increased risk of ICH compared with matched patients on DOACs (relative risk [RR] 1.43, 95% confidence interval [CI] 1.20-1.69) and patients not on anticoagulation (RR 1.36, 95% CI 1.15-1.61). We did not observe a difference in ICH between patients on DOACs compared with matched patients not on anticoagulation. In patients with ICH, 30-day mortality did not differ by anticoagulation status or type. Patients on warfarin had an increased hazard of neurosurgery compared with patients not on anticoagulation.. Patients on warfarin seen in the emergency department with a head injury had higher relative risks of ICH than matched patients on a DOAC and patients not on anticoagulation, respectively. The risk of ICH for patients on a DOAC was not significantly different compared with no anticoagulation. Further research should confirm that older adults using warfarin are the only group at higher risk of ICH after head injury.

Topics: Accidental Falls; Aged; Anticoagulants; Craniocerebral Trauma; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Intracranial Hemorrhages; Male; Ontario; Retrospective Studies; Warfarin

Intracranial hemorrhage (ICH) is a known complication in patients with ventricular assist devices (VAD). We present a case of a 42-year-old male with a VAD and on warfarin who presented to the emergency department with ICH necessitating anticoagulant reversal. An attenuated dose of 15 units/kg of 4-factor prothrombin complex-concentrates (4F-PCC) was given and the patient's coagulation profile was subsequently assessed using rotational thromboelastometry (ROTEM®) to determine appropriateness of reversal. ROTEM® analysis showed adequate reversal at the time of assessment and the patient ultimately returned home without further functional deficits, highlighting the role of ROTEM® to guide anticoagulation reversal in the VAD patient population.

Topics: Adult; Anticoagulants; Blood Coagulation Factors; Heart-Assist Devices; Humans; Intracranial Hemorrhages; Male; Thrombelastography; Warfarin

Inactivated four-factor prothrombin complex concentrate (I4F-PCC, Kcentra. This is a multicenter retrospective pragmatic registry study of adult patients admitted at a participating study site between January 1, 2014, and December 31, 2015, who received I4F-PCC for reversal of warfarin-related ICH. Practices around warfarin-related ICH reversal in context of I4F-PCC utilization are described, including repeat I4F-PCC dosing, adjunctive reversal agents, and dose rounding policies (i.e., rounding doses to nearest vial size vs preparing exact/unrounded doses). All research was approved by local human investigation committees at each institution.. Seventeen institutions contributed data on 528 patients to this registry. These institutions were primarily urban centers (74%), located in the southeast USA (47%), with Level 1 Trauma designation (79%), and with Comprehensive Stroke Center designation (74%). Most patients included in the study had sustained a non-traumatic ICH (68%), had a median admission GCS of 14 (IQR 7-15), and were receiving warfarin for atrial fibrillation (57.4%). There was substantial time latency between baseline INR and I4F-PCC (median 2.4 h, IQR 1.4-4.5 h). Most patients received adjunctive reversal agents, including vitamin K (89.5%) and fresh frozen plasma (FFP) (31.9%). A smaller proportion (6.0%) of patients received repeat I4F-PCC dosing. The median ICU length of stay (LOS) was 3 days (IQR 2-7 days), median hospital LOS was 6 days (IQR 3-12 days), and overall mortality rate was 28.8%. For institutions rounding doses to the nearest vial size, the first post-I4F-PCC dose INR was statistically but not clinically significantly lower than for institutions without vial size dose rounding, with comparable degrees of INR reduction from baseline. No differences were observed between dose rounding cohorts in adverse effects, ICU or hospital LOS, modified Rankin score at discharge, or mortality rates.. Most patients received single doses of I4F-PCC, with adjunctive reversal agents and rounding doses to vial size. The time difference from baseline INR to factor product administration is a potential opportunity for process improvement in the management of warfarin-related ICH.

Topics: Adult; Anticoagulants; Blood Coagulation Factors; Humans; International Normalized Ratio; Intracranial Hemorrhages; Retrospective Studies; Warfarin

Limited data support the benefits of non-vitamin K oral anticoagulants (NOACs) among atrial fibrillation patients with prior gastrointestinal bleeding (GIB). We aimed to evaluate the effectiveness and safety of NOACs compared with those of warfarin among atrial fibrillation patients with prior GIB.. Oral anticoagulant-naive individuals with atrial fibrillation and prior GIB between January 2010 and April 2018 were identified from the Korean claims database. NOAC users were compared with warfarin users by balancing covariates using the inverse probability of treatment weighting method. The primary outcomes were ischemic stroke, major bleeding, and the composite outcome (combined ischemic stroke and major bleeding). Fatal events from each outcome were evaluated as secondary outcomes.. A total of 42 048 patients were included (24 781 in the NOAC group and 17 267 in the warfarin group). The mean time from prior GIB to the initiation of oral anticoagulant was 3.1±2.6 years. After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups (mean age, 72 years; men, 56.8%; and mean CHA. NOACs were associated with lower risks of ischemic stroke and major bleeding than warfarin among atrial fibrillation patients with prior GIB.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Thromboembolism; Warfarin

Atrial fibrillation (AF) prevalence and its risk of stroke rise with ageing. We aimed to investigate the outcomes of NOAC and warfarin in AF patients aged ≥ 85 years.. This is a retrospective study using Taiwan National Health Insurance Research Database. A total of 15,361 patients aged ≥ 85 years with AF on oral anticoagulants were identified. The end points included ischaemic stroke, intracranial haemorrhage (ICH), major bleeding, all-cause mortality and composite adverse events (ICH or major bleeding or all-cause mortality). Clinical outcomes were compared between each NOAC and warfarin after propensity matching.. Before propensity matching, patients taking warfarin were older, more female with more comorbidities than NOACs users. After propensity matching, baseline characteristics did not differ significantly between matched subjects receiving warfarin and each NOAC. Compared to warfarin, dabigatran was associated with a lower risk of ICH (hazard ratio [HR] 0.496), mortality (HR 0.558) and adverse events (HR 0.628), while rivaroxaban was associated with a lower risk of ischaemic stroke (HR 0.781), ICH (HR 0.453), mortality (HR 0.558) and adverse events (HR 0.636). Apixaban was associated with a lower risk of mortality (HR 0.488) and adverse events (HR 0.557) compared to warfarin. (all P < .05).. For the efficacy, NOACs were associated with a comparable or lower risk of ischaemic stroke compared to warfarin. For adverse events, NOACs were associated with a lower risk of all-cause mortality and composite adverse events. In the elderly AF population, NOACs could be a more favourable choice for stroke prevention.

Topics: Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Mortality; Propensity Score; Pyrazoles; Pyridones; Stroke; Warfarin

This study aims to determine whether door-to-needle times (DNT) for reversal of anticoagulant-associated intracerebral haemorrhage (ICH) (1) have improved over time, (2) differ between warfarin and dabigatran and (3) are comparable to ischaemic stroke (IS) thrombolysis DNT, and (4) whether reversal is monitored.. Retrospective review of all warfarin- and dabigatran-associated ICH presenting to Christchurch Hospital over a 15-year period. DNT data from 2013-2018 were compared between warfarin-related ICH (WRICH), dabigatran-related ICH (DRICH) and IS thrombolysis.. 172 WRICH were identified. Over time there were significant reductions in door-to-first-reversal-agent (r=-0.21, p=0.01), scan-to-first-reversal-agent (r=-0.27, p=0.001) and scan-to-prothrombin-complex-concentrate (PCC) (r=-0.33, p=0.001) times. In the 2013-2018 cohort, WRICH had significantly slower DNT, door-to-scan time and scan-to-needle time compared to DRICH and IS thrombolysis (all p<0.001). There was no statistical difference between DRICH and IS. Median DNT was 183 minutes for WRICH, 72 minutes for DRICH and 52 minutes for IS. Median time to repeat international normalised ratio was 231 minutes, and the median time to repeat thrombin clotting time was 825 minutes.. Door-to-any-reversal-agent and scan-to-PCC times have improved over time, but they remain significantly longer than IS thrombolysis times. Monitoring of reversal is inadequate, particularly for WRICH receiving PCC.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Dabigatran; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; New Zealand; Retrospective Studies; Thrombolytic Therapy; Time Factors; Treatment Outcome; Warfarin

Real-world predictors of major bleeding (MB) have been well-studied among warfarin users, but not among all direct oral anticoagulant (DOAC) users diagnosed with atrial fibrillation (AF). Thus, our goal was to build a predictive model of MB for new users of all oral anticoagulants (OAC) with AF.. We identified patients hospitalized for any cause and discharged alive in the community from 2011 to 2017 with a primary or secondary diagnosis of AF in Quebec's RAMQ and Med-Echo administrative databases. Cohort entry occurred at the first OAC claim. Patients were categorized according to OAC type. Outcomes were incident MB, gastrointestinal bleeding (GIB), non-GI extracranial bleeding (NGIB) and intracranial bleeding within 1 year of follow-up. Covariates included age, sex, co-morbidities (within 3 years before cohort entry) and medication use (within 2 weeks before cohort entry). We used logistic-LASSO and adaptive logistic-LASSO regressions to identify MB predictors among OAC users. Discrimination and calibration were assessed for each model and a global model was selected. Subgroup analyses were performed for MB subtypes and OAC types.. Our cohort consisted of 14,741 warfarin, 3,722 dabigatran, 6,722 rivaroxaban and 11,196 apixaban users aged 70-86 years old. The important MB predictors were age, prior MB and liver disease with ORs ranging from 1.37-1.64. The final model had a c-statistic of 0.63 (95% CI 0.60-0.65) with adequate calibration. The GIB and NGIB models had similar c-statistics of 0.65 (95% CI 0.63-0.66) and 0.67 (95% CI 0.64-0.70), respectively.. MB and MB subtype predictors were similar among DOAC and warfarin users. The predictors selected by our models and their discriminative potential are concordant with published data. Thus, these models can be useful tools for future pharmacoepidemiologic studies involving older oral anticoagulant users with AF.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridones; Regression Analysis; Rivaroxaban; Warfarin

The intracranial hemorrhage (ICH) risk of oral anticoagulants/non-vitamin K antagonist oral anticoagulants (NOACs) remains largely unknown. Patients who need oral anticoagulants such as aspirin or warfarin often suffer from obvious complications.. This network meta-analysis intended to assess the ICH risk in patients taking NOACs. The data from PubMed, the Cochrane database, and Embase were reviewed. All phase III randomized controlled trials of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), aspirin and warfarin were reviewed.. Twenty-three trials involving 137,713 participants were included, involving 6 regimens. Warfarin had the first risk of ICH (surface under the cumulative ranking area: 0.82), followed by dabigatran, edoxaban, aspirin, apixaban, rivaroxaban, and placebo. Dabigatran had the lowest risk of all-cause mortality (surface under the cumulative ranking area: 0.63), followed by apixaban, edoxaban, warfarin, rivaroxaban, aspirin, and placebo.. Warfarin significantly increased the risk of ICH in patients taking oral anticoagulants compared with 4 NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) and aspirin. Apixaban is least likely to induce all-cause mortality.

Topics: Administration, Oral; Antithrombins; Aspirin; Clinical Trials, Phase III as Topic; Humans; Intracranial Hemorrhages; Mortality; Network Meta-Analysis; Randomized Controlled Trials as Topic; Risk Assessment; Warfarin

Low dose direct acting oral anticoagulants (LDDOACS) were approved for elderly atrial Fibrillation (AF) patients with limited information. A retrospective analysis collecting baseline characteristics and outcomes in AF patients ≥ 80 prescribed LDDOAC or warfarin (W), from a multidisciplinary practice between 1/1/11 (First LDDOAC available) and 5/31/17 was conducted. From 9660 AF patients, 514 ≥ 80 received a LDDOAC and 422 W. A multivariable comparison found LDDOAC patients were older (p <0.001), had lower creatinine clearance (CrCl) (p = 0.006), used more anti-platelet drugs (p <0.001), and more often had new onset AF verses those prescribed W (p <0.001). There were no clinically significant differences among those patients receiving Dabigatran 75 mgs BID (D), Rivaroxaban 15mgs (R) or Apixaban 2.5mgs BID (A). Forty-eight and 50% of the patients remained on their LDDOAC or W for the observation period (p = 0.55). Stroke/systemic embolism (SSE) and CNS bleeds were 1.16 vs 2.22%/yr., (p = 0.143) and 1.46 vs 0.93%/yr., (p = 0.24). Mortality and major bleeds were 6.26 vs 1.67%/yr., and 12.3vs 3.77%/yr. (p <0.001). SSE were 1.1%/yr for D, R, and A (p = 0.94). CNS bleeds were 2.2 for D, 1.7 for R and 0.8%/yr. for A: p = 0.53. Major bleeding was: 14.3 for D, 14.1 for R and 9.1%/yr. for A, p = 0.048 (with A < R, p = 0.01). Mortality was 5.5 for D, 4.2 for R and 9.5% for A, p = 0.031. In conclusion, half the patients remained on their assigned anti-coagulant. SSE and intracranial bleed rates were similar and low. Major bleeds and deaths were different between groups emphasizing the need for prospective randomized trials in this growing population with AF.

Topics: Age Factors; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Multivariate Analysis; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Four-factor prothrombin complex concentrate (4PCC) is the preferred reversal agent for warfarin reversal, although the ideal dose is unknown. Fixed-dose 4PCC offers simplified dosing compared to standard-dosing algorithms with potentially lower risks of thromboembolic complications given lower doses are typically utilized.. Retrospective, observational, multicentered, pre- post- study of patients who received 4PCC for warfarin reversal among four hospitals within the same regional health system. Standard-dose patients received variable doses ranging from 25 to 50 units/kg based on total body weight and initial INR and fixed-dose patients received 2000 units. The primary outcome was achievement of a target INR ≤ 1.4 on the first post-4PCC INR result.. After exclusions, 48 and 42 patients were analyzed in the standard-dose and fixed-dose groups, respectively. There was no difference in the ability to achieve a target INR of ≤1.4 (82.6% vs 81.5%, p = 0.14). Both groups received the same median dose of 2000 units, although fixed-dose patients actually received a higher weight-based dose than standard-dose patients (27 units/kg vs 24.5 units/kg).. A fixed-dose 4PCC regimen of 2000 units among patients with ICH was as effective as standard-dose 4PCC for INR reversal among patients with ICH. However, fixed-doses of 2000 units at times exceeded standard 4PCC doses which may be contradictory to the goals of fixed-dose 4PCC for warfarin reversal.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Statistics, Nonparametric; Warfarin

Globally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were <20 years old, who were not using OACs 6 months prior to ICH, or who had a CHA2DS2-VASc score of ≤1. We also excluded patients who died during admission for ICH, with follow-up for <6 weeks after discharge, or who started OAC >6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20-0.76) and IS/SE (HR = 0.12, 95% CI = 0.03-0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34-0.93) and IS/SE (HR = 0.26, 95% CI = 0.09-0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Female; Hospitalization; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Factors; Taiwan; Warfarin; Young Adult

Head injury is a frequent reason for admission to the emergency department. In parallel, there is a growing use of anticoagulants in an increasingly aging population, which renders this particular group of trauma patients more frequent. In several countries, including Portugal, a 24-h surveillance period followed by repetition of head computed tomography (CT) is the standard procedure for these patients. However, these recommendations have not been based on studies of prevalence of intracranial hemorrhages in control head CTs, namely in this group of anticoagulated patients. This study intends to evaluate the prevalence of de novo intracranial hemorrhages in control head CTs in anticoagulated patients.. An observational study was carried out, which included patients admitted to Hospital de Braga between June 2017 and January 2018, victims of head injury and on anticoagulation therapy, whose admission head CT excluded intracranial hemorrhage.. We collected a total of 201 patients, with a mean age of 81.6 years, and 57.5% of them were prescribed warfarin; 181 of these patients repeated the head CT 24 h later. Of these 181 patients, 3 (1.66%) exhibited intracranial hemorrhage in control CT, without surgical indication. All patients were followed up 1 month after the trauma, and there was no readmission requiring hospitalization, surgery or death.. In conclusion, de novo intracranial hemorrhage in control head CT of anticoagulated patients is rare. We propose that these patients may be discharged if the admission CT does not reveal intracranial hemorrhage, providing that they are accompanied by a caregiver and informed about red flags.

Topics: Aged; Anticoagulants; Craniocerebral Trauma; Humans; Infant, Newborn; Intracranial Hemorrhages; Retrospective Studies; Tomography, X-Ray Computed; Warfarin

Antithrombotic therapy is administered after left ventricular assist device (LVAD) implantation to prevent thromboembolic events. Intracranial hemorrhage (ICH) is a life-threatening adverse event requiring immediate discontinuation of antithrombotics. We investigated the timing of antithrombotic resumption after ICH in patients with LVADs and the association between timing and risk of recurrent hemorrhage and thrombotic events.. We performed a multicenter, retrospective analysis of patients with ICH occurrence during LVAD antithrombotic regimen with subsequent resumption of antithrombotics from January 1, 2010, to December 31, 2017. Covariates included age, international normalized ratio, antithrombotic dosing, timing of resumption, modified Rankin score, and subsequent hemorrhagic and thrombotic events within 1 year post-ICH. Patients who did not resume anticoagulation were excluded.. Of 673 patients with LVADs, 85 (12.6%) developed ICH while being treated with antithrombotics. Forty-three were excluded due to death prior to resumption and one due to lack of resumption. The remaining 41 patients were on antithrombotics with a median (interquartile range [IQR]) international normalized ratio at ICH onset of 2.6 (1.8-3.6). Aspirin and warfarin were resumed at a median (IQR) of 5.5 (1.3-8.8) and 6.5 (4.0-15.5) days post-ICH, respectively. A continuous unfractionated heparin infusion was initiated in 16 (39.0%) patients at a median (IQR) of 2.5 (1.0-7.8) days post-ICH. During the 1-year follow-up after anticoagulation resumption, 11 (26.8%) patients suffered secondary hemorrhages and two (4.9%) suffered secondary thrombotic events. Using Kaplan-Meier method and log-rank test, we compared all patients who resumed anticoagulation by 6 days post-ICH to those who resumed after 6 days. There was no difference in freedom from secondary hemorrhagic event between the two groups (P = 0.75).. Despite timing of resumption of antithrombotic therapy after ICH, recurrent hemorrhagic events can be expected in one-quarter of these patients over the subsequent year.

Topics: Aged; Anticoagulants; Aspirin; Deprescriptions; Female; Fibrinolytic Agents; Heart Failure; Heart-Assist Devices; Heparin; Humans; International Normalized Ratio; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Thromboembolism; Time Factors; Warfarin

Patients with mechanical heart valves are at high thrombotic risk and require warfarin. Among those developing intracranial hemorrhage, limited data are available to guide clinicians with antithrombotic reinitiation. This 13-patient case series of warfarin-associated intracranial hemorrhages found the time to reinitiate antithrombotic therapy (17 days, interquartile range 21.5 days), and changes to international normalized ratio targets were variable and neither correlated with the type, location, or etiology of bleed, nor the valve and associated thromboembolic risk. The initial presentation significantly impacted prognosis, and diligent assessment and follow-up may support positive long-term outcomes.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Aortic Valve; Aspirin; Blood Coagulation Factors; Cerebral Hemorrhage; Female; Heart Valve Prosthesis; Hematoma, Subdural; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Mitral Valve; Plasma; Platelet Aggregation Inhibitors; Pregnancy; Retrospective Studies; Subarachnoid Hemorrhage; Subarachnoid Hemorrhage, Traumatic; Thromboembolism; Vitamin K; Warfarin

Background and Purpose- Warfarin is associated with a better net clinical benefit compared with no treatment in patients with nonvalvular atrial fibrillation (AF) and history of intracranial hemorrhage (ICH). There are limited data on nonvitamin K antagonist oral anticoagulants (NOACs) in these patients, especially in the Asian population. We aimed to compare the effectiveness and safety of NOACs to warfarin in a large-scale nationwide Asian population with AF and a history of ICH. Methods- Using the Korean Health Insurance Review and Assessment database from January 2010 to April 2018, we identified patients with oral anticoagulant naïve nonvalvular AF with a prior spontaneous ICH. For the comparisons, warfarin and NOAC groups were balanced using propensity score weighting. Ischemic stroke, ICH, composite outcome (ischemic stroke+ICH), fatal ischemic stroke, fatal ICH, death from composite outcome, and all-cause death were evaluated as clinical outcomes. Results- Among 5712 patients with AF with prior ICH, 2434 were treated with warfarin and 3278 were treated with NOAC. Baseline characteristics were well-balanced after propensity score weighting (mean age 72.5 years and CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Proportional Hazards Models; Recurrence; Republic of Korea; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

To determine and compare the rates of acute intracranial haemorrhage (ICH) in emergency computed tomography (CT) head studies performed on patients treated with either warfarin or a direct-acting oral anticoagulant agent (DOAC) in a real-world acute setting from a radiology service perspective.. A retrospective automated search was undertaken via the hospital's radiology information system (RIS) for emergency CT head studies performed over a 2-year period where the clinical details indicated treatment with warfarin or a DOAC. The report of each scan was reviewed for the presence of unequivocal ICH. Duplicate and follow-up scans were excluded. Other parameters (trauma history and time of scan) were also reviewed.. Following exclusions, 2,359 cases were eligible for analysis; 1,822 patients were treated with warfarin and 537 treated with DOACs. One hundred and nineteen CT heads, of which 104 were treated with warfarin and 15 treated with DOACs, were positive for various types of ICH. The positive rate for ICH was lower in the DOACs group than the warfarin group; 2.7% (number needed to scan: 37) versus 5.7% (number needed to scan: 17.5; p=0.0067). This is also true in a cohort of patients who had traumatic head injury; 2.14% (number needed to scan: 46.7) versus 5.80% (number needed to scan: 17.2; p=0.02).. The present study has shown a lower rate of ICH in patients treated with DOACs compared to those treated with warfarin in an acute setting. A similar trend is demonstrated in a cohort of patients with a history of traumatic head injury.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Warfarin

Guidelines for imaging anticoagulated patients following a traumatic injury are unclear. Interval CT head (CTH) is often routinely performed after initial negative CTH to assess for delayed intracranial hemorrhage (ICH-d). The rate of ICH-d for patients taking novel oral anticoagulants (NOACs) is unknown. We hypothesized that the incidence of ICH-d in patients on NOACs would be similar, if not lower to that of warfarin, and routine repeat CTH after initial negative would not change management, and thus, may not be indicated.. Anticoagulated patients presenting with blunt trauma to a level I trauma center between 2016 and 2018 were evaluated. Exclusion criteria included: positive initial CTH and those taking nonoral anticoagulation or antiplatelet agents alone (without warfarin or NOAC). Outcomes included: ICH-d, discharge GCS, administration of reversal agents, neurosurgical intervention, readmission, and death. Multivariable regression was performed to evaluate patient factors associated with the development of ICH-d.. A total of 332 patients met the inclusion criteria. Patients were divided into a warfarin group (n = 191) and NOAC group (n = 141). The incidence of ICH-d in the warfarin group was 2.6% (5/191) and 2.1% (3/141) in the NOAC group (P = 0.77). There were no reversal agents administered, neurosurgical interventions, readmissions, or deaths in the NOAC group.. Little is known about the impact of NOACs in the setting of trauma, especially regarding risks of ICH-d following traumatic injury. In the NOAC group, ICH-d occurred only 2.1% of the time. In addition, there were no reversal agents given, neurosurgical interventions, or deaths. These data, taken together, suggest the limited utility of repeat imaging in this patient population.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Head; Head Injuries, Closed; Humans; Incidence; Intracranial Hemorrhages; Male; Neurosurgical Procedures; Patient Readmission; Practice Guidelines as Topic; Tomography, X-Ray Computed; Trauma Centers; Warfarin

The Safety of Oral Anticoagulants Registry (SOAR) was designed to describe the evaluation and management of patients with oral anticoagulant (OAC)-related major bleeding or bleeding concerns who present to the emergency department (ED) with acute illness or injury. Patients in the ED are increasingly taking anticoagulants, which can cause bleeding-related complications as well as impact the acute management of related or unrelated clinical issues that prompt presentation. Modifications of emergency evaluation and management due to anticoagulation have not previously been studied.. This was a multicenter observational in-hospital study of patients who were judged to be experiencing an active OAC effect and had (a) an obvious bleeding event or (b) were deemed at risk for serious bleeding spontaneously, after injury, or during an indicated invasive procedure. Diagnostic testing, therapies employed, and clinical outcomes were collected.. Thirty-one US hospitals contributed data to SOAR. Of 1513 subjects, acute hemorrhage (AH) qualified 78%, while 22% had a bleeding concern (BC). Warfarin was the index OAC in 37.3%, dabigatran in 13.3%, and an anti-Factor X. Care of anticoagulated patients in the acute care setting is inconsistent, reflecting the diversity of presentation. As the prevalence of OAC use increases with the aging of the US population, further study and targeted educational efforts are needed to drive more evidence-based care of these patients.

Topics: Aged; Aged, 80 and over; Dabigatran; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Registries; Warfarin

Incidence of delayed intracranial hemorrhage (DICH) in patients on warfarin has been controversial. No previous literature has reported the utility of international normalized ratio (INR) in predicting traumatic DICH.. Utilizing INR to risk stratify head trauma patients who may be managed without repeat imaging.. This was a retrospective study at a Level II trauma center. All patients on warfarin with head injuries from March 2014 to December 31, 2017 were included. Each patient underwent an initial head computed tomography scan (HCT) and subsequent repeat HCT 12 h after. Patients presenting > 12 h after head injury received only one HCT. Two blinded neuroradiologists reviewed each case of DICH. Statistical analysis evaluated Glasgow Coma Scale (GCS), Injury Severity Score (ISS), heart rate, systolic blood pressure (SBP), age, and platelet count.. There were 395 patients who qualified for the protocol; 238 were female. Average age was 79 years. Seventy-seven percent of patients underwent repeat HCT. Five resulted in DICH (INR 2.6-3.0), three of which might have been present on initial HCT; incidence rate of 0.51-1.27%. One patient required neurosurgical intervention. Among 80 patients with INR < 2, no DICH was identified, resulting in high sensitivity, but with a wide confidence interval; sensitivity of 100% (95% confidence interval [CI] 47.8-100), specificity 21% (95% CI 16.6-28.9). Correlation of factors: ISS (p = 0.039), GCS (p = 0.978), HR (p = 0.601), SBP (p = 0.198), age (p = 0.014), and platelets (p = 0.281).. No patient with INR < 2 suffered DICH, suggesting that warfarin users presenting with INR < 2 may be managed without repeat HCT. For INR > 2, patients age and injury severity can be used for shared decision-making to discharge home with standard head injury precautions and no repeat HCT.

Topics: Aged; Anticoagulants; Craniocerebral Trauma; Female; Glasgow Coma Scale; Humans; Injury Severity Score; International Normalized Ratio; Intracranial Hemorrhages; Male; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Tomography, X-Ray Computed; Trauma Centers; Warfarin

The number of trauma patients on prehospital novel oral anticoagulants (NOACs) is increasing. After an initial negative computed tomography of the head (CTH), practice patterns are variable for obtaining repeat CTH to evaluate for delayed intracranial hemorrhage (ICH-d). However, the risks and outcomes of ICH-d for patients on NOACs are unclear. We hypothesized that, for these patients, the incidence of ICH-d is low, similar to that of warfarin, and when it occurs, it does not result in clinically significant worse outcomes.. Five level 1 trauma centers in Northern California participated in a retrospective review of anticoagulated trauma patients. Patients were included if their initial CTH was negative. Primary outcomes were incidence of ICH-d, neurosurgical intervention, and death. Patient factors associated with the outcome of ICH-d were determined by multivariable regression.. From 2016 to 2018, 777 patients met the inclusion criteria (NOAC, n = 346; warfarin, n = 431), 54% of whom received a repeat CTH. Delayed intracranial hemorrhage incidence was 2.3% in the NOAC group and 4% in the warfarin group (p = 0.31). No NOAC patient with ICH-d required neurosurgical intervention or died because of their head injury. Two warfarin patients received neurosurgical intervention, and three died from their head injury. Head Abbreviated Injury Scale ≥3 was associated with increased odds of developing ICH-d (adjusted odds ratio, 32.70; p < 0.01).. The incidence of ICH-d in patients taking NOAC is low. In this study, patients on NOACs who developed ICH-d after an initial negative CTH did not need neurosurgical intervention or die from their head injury. Repeat CTH in this patient population does not appear necessary.. Prognostic/epidemiologic study, level III.Therapeutic, level IV.

Topics: Administration, Oral; Anticoagulants; California; Craniocerebral Trauma; Humans; Incidence; Intracranial Hemorrhages; Practice Patterns, Physicians'; Prognosis; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Unnecessary Procedures; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Warfarin

Current guidelines recommend the use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). Data regarding warfarin sodium use compared with NOAC use in patients with AF with a history of intracranial hemorrhage (ICH) are limited.. To compare the clinical outcomes of warfarin use and NOAC use in patients with AF with a history of ICH using a nationwide cohort with AF.. A nationwide cohort study from January 1, 2012, to December 31, 2016, was performed using data from the Taiwan National Health Insurance Research Database. The dates of analysis were July 1 to September 1, 2019. The study population comprised patients with AF with a history of ICH and a CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, prior stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease], age 65-74 years, sex category [female]) of at least 1 for men or at least 2 for women who had received warfarin or NOACs. The clinical outcomes were examined using Cox proportional hazards regression analyses among the study population before and after propensity score matching.. Oral anticoagulation with warfarin or NOACs.. The clinical outcomes measured were all-cause mortality, ischemic stroke, ICH, major bleeding, and adverse events.. The study cohort included 4540 patients (mean [SD] age, 76.0 [10.5] years; 2653 men [58.4%]), with 1047 patients receiving warfarin (mean [SD] age, 75.1 [11.4] years; 571 men [54.5%]) and 3493 patients receiving NOACs (mean [SD] age, 76.3 [10.2] years; 2082 men [59.6%]). Compared with warfarin use, NOAC use was associated with statistically significantly lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.517; 95% CI, 0.457-0.585), ICH (aHR, 0.556; 95% CI, 0.389-0.796), and major bleeding (aHR, 0.645; 95% CI, 0.525-0.793), whereas the rate of ischemic stroke was similar in the 2 groups (aHR, 0.879; 95% CI, 0.678-1.141). These results were generally consistent after propensity score matching among 973 patients in each group.. Among patients with AF with prior ICH, NOAC use was associated with lower rates of ICH and major bleeding compared with warfarin use, whereas the rate of ischemic stroke was similar in the 2 groups. Among patients with AF with prior ICH, NOACs could be the preferred choice for stroke prevention.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Cohort Studies; Comorbidity; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Risk Factors; Stroke; Taiwan; Warfarin

Black patients are under-represented in randomized trials evaluating oral anticoagulants in non-valvular atrial fibrillation (NVAF). We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in African Americans with NVAF.. We performed an analysis using Optum® De-Identified Electronic Health Record (EHR) data from 1/1/2012-9/30/2018. We included adult African American patients with a diagnosis of NVAF who were anticoagulant-naïve during the 12-months prior to initiation of rivaroxaban or warfarin. Patients receiving rivaroxaban were 1:1 propensity score matched to warfarin patients. Our primary effectiveness and safety outcomes were the 2-year incidence rates (%/year) of stroke or systemic embolism (SSE) and major bleeding using an intention-to-treat approach. Cohorts were compared using doubly-robust Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).. We matched 4102 rivaroxaban and 4102 warfarin users with a median (interquartile range) available follow-up of 2.0 (0.9, 2.0) years. Median CHA2DS2-VASc and HASBLED scores were 3 (2, 4) and 2 (1, 3). Rivaroxaban use was associated with a lower risk of SSE (1.99 versus 2.48, HR = 0.77, 95%CI = 0.60-0.99), ischemic stroke (1.84 versus 2.37, HR = 0.76, 95%CI = 0.59-0.98) and major bleeding (4.22 versus 4.98, HR = 0.84, 95%CI = 0.70-0.99). No differences in intracranial hemorrhage or gastrointestinal bleeding were observed. Neither sensitivity analyses utilizing an on-treatment methodology nor inverse probability-of-treatment weighting showed significant differences in SSE or major bleeding between rivaroxaban and warfarin users.. Rivaroxaban appeared at least as effective and safe as warfarin when used to manage African American patients with NVAF in routine practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Black or African American; Embolism; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Management of warfarin-associated major haemorrhage in prosthetic valve diseases is difficult as there is a fine line between haemorrhage and thrombosis. An individual's propensity towards thrombosis, such as pregnancy, makes this situation even more complicated. Cases like these are very rare in the literature.. A 26 weeks pregnant, gravida two, para one, 35-year-old patient with prosthetic aortic and mitral valves presented to an external emergency clinic with clouding of consciousness. Her international normalised ratio(INR) was 8.9 at presentation. Brain MRI revealed a left subdural haematoma with no significant mass effect. Warfarin treatment was discontinued. On the second day of follow-up, she was referred to our centre for further evaluation of her clinical deterioration. She was haemodynamically stable on admission to the intensive care unit and followed up with a stable condition until the fourth day when she developed right eye drop and subsequent loss of consciousness. Her haematoma was surgically evacuated, and her condition improved. Eventually, she and a healthy newborn were discharged.. Intracranial haemorrhage during pregnancy is a relatively rare complication that requires a multidisciplinary management plan. Although the thrombogenic risk is high, it is vital to complete a reversal of warfarin anticoagulation in pregnant women with major bleeding.

Topics: Adult; Anticoagulants; Aortic Valve; Female; Heart Valve Prosthesis Implantation; Humans; Intracranial Hemorrhages; Live Birth; Mitral Valve; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombosis; Treatment Outcome; Warfarin

Evaluate reversal strategies in atrial fibrillation (AF) patients with warfarin-associated intracranial hemorrhage (ICH) in clinical care.. Observational cohort of AF patients with warfarin-associated ICH at two referral hospitals (2007-2010), with patient features, reversal agents, and outcomes collected from medical records.. Among 498 ICH patients 403 received fresh frozen plasma (FFP) without 3-factor prothrombin complex concentrates (PCCs) or recombinant factor VIIa (rFVIIa), 65 received PCCs or rFVIIa, mostly with FFP, and 30 received no acute reversal agents. Median time from presentation to reversal agent administration was 3.4 h (IQR 2.3-5.3). INR was reversed to ≤1.4 by 6 h post-presentation in 46% of patients receiving PCCs/rFVIIa versus 15% receiving FFP alone (p<0.0001). Among PCCs/rFVIIa recipients, 31% died in-hospital vs. 24% receiving FFP alone (p=0.27). Adjusted OR for death accounting for age and Glasgow Coma Score was 0.78 (0.36-1.69) for PCCs/rFVIIa vs FFP only and 1.16 (0.59-2.27) comparing those reaching vs. not reaching INR ≤ 1.4 at 6 h.. Treatment with PCCs/rFVIIa led to faster INR reversal than treatment with FFP alone. Neither treatment with PCCs/rFVIIa nor rapid INR reversal was associated with improved survival. Delays receiving PCCs may largely eliminate the benefit of treatment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Factors; Boston; Coagulants; Factor VIIa; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Plasma; Retrospective Studies; Time Factors; Treatment Outcome; Warfarin

In patients with acute ischemic stroke and atrial fibrillation, treatment with low molecular weight heparin increases early hemorrhagic risk without reducing early recurrence, and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage.. We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations.. We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 patients who met the DOAC versus warfarin analysis inclusion criteria. In adjusted Cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01-7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63-2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29-0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22-1.48]).. Our study suggests that patients with ischemic stroke and atrial fibrillation would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Embolism; Female; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Neuroimaging; Recurrence; Registries; Retrospective Studies; Risk Assessment; Stroke; Treatment Outcome; United States; Warfarin

There are various patterns in determining the choice of the first-line antithrombotic agent for acute stroke with non-valvular atrial fibrillation. We investigated the efficacy and safety of non-vitamin K oral anticoagulants as first-line antithrombotics for patients with acute stroke and non-valvular atrial fibrillation.. Patients with non-valvular atrial fibrillation and ischemic stroke or transient ischemic attack within 24 h from stroke onset were included. On the basis of the first regimen used and the regimen within 7 days after admission, the study population was divided into three groups: 1) antiplatelet switched to warfarin (A-W), 2) antiplatelet switched to NOAC (A-N), and 3) NOAC only (N only). We compared the occurrence of early neurologic deterioration, symptomatic intracranial hemorrhage, systemic bleeding, and poor functional outcome at 90 days.. Of 314 included patients, 164, 53, and 97 were classified into the A-W, A-N, and N only groups, respectively. Early neurologic deterioration was most frequently observed in the A-W group (9.1%), followed by the A-N (5.7%) and N only (1.0%) groups (p = 0.017). Multivariable analysis adjusting for potential confounders demonstrated that the N only group was independently associated with a lower rate of early neurologic deterioration (odds ratio [OR] 0.104, 95% CI 0.013-0.831) or poor functional outcome at 90 days (OR 0.450, 95% CI 0.215-0.940) than the A-W group. However, the rate of symptomatic intracranial hemorrhage or any systemic bleeding event did not differ among the groups.. Using non-vitamin K oral anticoagulants as the first-line regimen for acute ischemic stroke may help prevent early neurologic deterioration without increasing the bleeding risk.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Disability Evaluation; Drug Substitution; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Recovery of Function; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

Ischemic stroke (IS) and major bleeding, which are serious adverse events in patients with atrial fibrillation (AF), could have seasonal variations, but there are few reports.Methods and Results:In the Shinken Database 2004-2016 (n=22,018), 3,581 AF patients (average age, 63.5 years; 2,656 men, 74.2%; 1,388 persistent AF, 38.8%) were identified. Median CHADS. Significant seasonal variations were observed for IS, ECH, and ICH events in AF patients, and were consistently the highest in winter. A small peak of ECH was observed in summer, which seemed, in part, to be related to increased DOAC use.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Comorbidity; Female; Follow-Up Studies; Humans; Incidence; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Risk Factors; Seasons; Tokyo; Treatment Outcome; Warfarin

The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited.. We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years.. Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated.. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively).. NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Topics: Aged, 80 and over; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Republic of Korea; Stroke; Thiazoles; Vitamin K; Warfarin

Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal.. This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications.. A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC.. A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Topics: Aged; Aged, 80 and over; Blood Coagulation Factors; Chi-Square Distribution; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Warfarin

Current guidelines favor 4F-PCC over plasma for reversal of warfarin. Uncertainty remains on the hemostatic effectiveness and thrombotic risk of 4F-PCC for direct-acting oral anticoagulants (DOACs), particularly in patients with intracranial hemorrhage (ICH). This study sought to evaluate the effectiveness and safety of a lower dose protocol of 25 units/kg 4F-PCC for the management of DOAC-associated ICH in a real-world setting.. This was a retrospective study of adult patients who received at least one dose of 4F-PCC from March 2014 to December 2015 for DOAC-associated ICH. The primary outcome was hemostatic effectiveness within 24 hours. The secondary outcome was thromboembolic events within 14 days.. Twenty-two patients received 4F-PCC for DOAC-associated ICH and were included in the analysis. Hemostasis was evaluable in 19 patients with post-4F-PCC imaging available and occurred in 18/19 (94.7%) patients. Thromboembolism occurred in 2 out of 22 patients (9.1%).. The use of a lower dose protocol of 25 units/kg of 4F-PCC resulted in high rates of hemostasis in patients with DOAC-associated ICH. Two patients developed thrombotic events within 14 days of 4F-PCC administration.

Topics: Anticoagulants; Blood Coagulation Factors; Humans; Intracranial Hemorrhages; Retrospective Studies; Warfarin

The Achilles heel of mechanical valves appears to be the need for anticoagulation. Several different types of mechanical valves have come and gone. The success or lack thereof of these valves depended on their various designs. We compared the two most promising mechanical valves of different eras and the need for anticoagulation through a case review. Both the Medtronic-Hall tilting disc valve and the bileaflet On-X valve were compared and contrasted in terms of durability and management of anticoagulation in high-risk patient populations. We present two cases of challenging anticoagulation management: a patient who underwent a mitral valve replacement with a Medtronic-Hall tilting disc valve who was off anticoagulation for close to six years, and a patient who underwent On-X mitral and aortic valve replacements and suffered a subsequent intracranial bleed requiring surgical intervention. We explore the ethical dilemmas associated with these patients and the risk of restarting anticoagulation for each.

Topics: Adult; Anticoagulants; Aortic Valve; Bioethical Issues; Bioprosthesis; Drug Administration Schedule; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Intracranial Hemorrhages; Loeys-Dietz Syndrome; Lung Diseases; Male; Middle Aged; Mitral Valve; Postoperative Complications; Prosthesis Design; Prosthesis Failure; Retreatment; Time Factors; Warfarin

The purpose of the study is to evaluate the impact of validation on the identification of major bleeding events in The Health Improvement Network (THIN) database in patients receiving anticoagulant therapy.. Patients aged 2 to 89 years with a first prescription for an anticoagulant (rivaroxaban or warfarin) between 2012 and 2015 were identified in THIN. Major bleeding events, defined as bleeding events necessitating hospitalization or referral to accident and emergency services or a specialist clinic, were identified using a 2-step ascertainment process based on read codes only, and then validated using a 2-step process requiring manual review of patients' records.. The positive predictive value for the ascertainment of major intracranial (IC) bleeds using only read codes was 96.9%, compared with 70.4% for gastrointestinal (GI) bleeds and 64.1% for urogenital (UG) bleeds. The incidence rate of major IC bleeding events was therefore similar when it was calculated before and after validation (0.32 per 100 person-years and 0.31 per 100 person-years, respectively). The incidence rate of major GI bleeds identified using read codes alone was reduced following validation from 2.05 to 0.94 per 100 person-years, and that of major UG bleeds decreased from 2.45 to 1.11 per 100 person-years.. Major GI and UG bleeding events ascertained from THIN using read codes require validation using additional information to prevent outcome misclassification. The absence of validation may lead to overestimated incidence rates of major bleeding for GI and UG bleeds.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Emergency Service, Hospital; Female; Female Urogenital Diseases; Gastrointestinal Hemorrhage; Hospitalization; Humans; Incidence; Intracranial Hemorrhages; Male; Male Urogenital Diseases; Middle Aged; Predictive Value of Tests; Primary Health Care; Registries; Risk Assessment; Risk Factors; Rivaroxaban; Validation Studies as Topic; Warfarin; Young Adult

Ischemic stroke and major bleeding, mostly due to intracranial hemorrhage (ICH), cause about the same rates of death in pivotal randomized trials of direct oral anticoagulants (DOACs) versus warfarin for stroke prevention in atrial fibrillation (AF). We analyzed our AF inpatient database to determine whether any ICH-related deaths were potentially preventable. Among 5008 patients admitted to our institution between May 2008 and September 2014 with a diagnosis of AF, eight had fatal ICH between admission and 90 days follow-up. The mean age of these patients was 85 years; 62% were male. Localization of the ICH was intraparenchymal in 62% and subdural in 38%. CHA

Topics: Accidental Falls; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Databases, Factual; Female; Humans; Inpatients; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Essentials Uncertainty remains about antiplatelets for vascular access patency in hemodialysis patients. 95 971 people under hemodialysis were followed in a claims database in Taiwan. Aspirin reduced vascular access failure rate and did not increase major bleeding rate. Clopidogrel, Aggrenox, and warfarin might increase major bleeding rate. SUMMARY: Background Dialysis adequacy is a major determinant of survival for patients with end-stage renal disease. Good vascular access is essential to achieve adequate dialysis. Objectives This study evaluated the impacts of different drugs on the vascular access failure rate of an arteriovenous fistula or an arteriovenous graft and the rate of major bleeding in hemodialysis patients. Patients and methods We studied patients with end-stage renal disease registered in the Taiwan National Health Insurance program from 1 January 1997 to 31 December 2012. A total of 95 971 patients were enrolled in our study. Vascular access dysfunction was defined as the need for thrombectomy or percutaneous angioplasty. Major bleeding was defined as emergency department visits or hospitalization with a primary diagnosis of gastrointestinal bleeding or intracerebral hemorrhage. The adjusted odds ratios between person-quarters with or without antiplatelet or oral anticoagulant use were calculated using a generalized estimating equation. Results The odds ratio of vascular access failure was 0.21 (0.11-0.39) for aspirin, 0.76 (0.74-0.79) for clopidogrel, 0.67 (0.59-0.77) for dipyridamole, 0.67 (0.53-0.86) for Aggrenox and 0.96 (0.90-1.03) for warfarin. The highest odds ratio for intracerebral hemorrhage was 5.33 (1.25-22.72) in younger patients using Aggrenox. The highest odds ratio for gastrointestinal bleeding was 1.34 (1.10-1.64) for clopidogrel. Conclusion Antiplatelet agents, but not warfarin, might reduce the vascular access thrombosis rate. The gastrointestinal bleeding rate was increased in the group using clopidogrel. Aggrenox should be used with caution in young individuals because it might increase the rate of intracerebral hemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arteriovenous Shunt, Surgical; Aspirin; Aspirin, Dipyridamole Drug Combination; Blood Vessel Prosthesis Implantation; Clopidogrel; Databases, Factual; Female; Gastrointestinal Hemorrhage; Graft Occlusion, Vascular; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Protective Factors; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Thrombosis; Treatment Failure; Warfarin; Young Adult

Antithrombotic therapy, including direct oral anticoagulants, is recommended in patients with non-valvular atrial fibrillation (NVAF) who are at intermediate-to-high risk of stroke. The aims of this study were to assess the patterns of oral anticoagulant (OAC) prescription in Japanese patients with NVAF and compare the effectiveness and safety of dabigatran and warfarin.. This was a retrospective observational study of adults with NVAF who initiated dabigatran or warfarin between March 14, 2011 and June 30, 2016, using electronic claims data of approximately 12.94 million patients from 230 hospitals. Propensity score matching was used to derive equal patient cohorts. Outcomes included the combined incidence of stroke, systemic embolism, and intracranial bleeding (primary endpoint) and the incidence of major bleeding (secondary endpoint).. Overall, 400,884 patients were included. Among those prescribed an OAC, warfarin was the most common (34.3%). For the comparison of dabigatran and warfarin, 4606 patients were propensity-score matched in each cohort. Dabigatran recipients had lower incidences of stroke, systemic embolism, and intracranial bleeding [29.0 vs. 35.6 per 1000 patient-years; hazard ratio (HR), 0.72; 95% confidence interval (CI): 0.53-0.97; p=0.031] and major bleeding (6.4 vs. 11.3 per 1000 patient-years; HR, 0.55; 95% CI: 0.30-0.99; p=0.048). The most common type of bleeding in both groups was gastrointestinal and the incidence was lower in dabigatran recipients (1.6 vs. 6.4 per 1000 patient-years; HR, 0.24; 95% CI: 0.08-0.69; p=0.009).. In Japan, dabigatran was associated with a lower risk of stroke, systemic embolism, and intracranial bleeding and major bleeding compared with warfarin in patients with NVAF.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comparative Effectiveness Research; Dabigatran; Databases, Factual; Embolism; Female; Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Japan; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

This retrospective study investigated the efficacy and safety of prothrombin complex concentrates (PCCs) for management of major bleeding events (MBE) in 344 patients receiving the anticoagulants rivaroxaban, apixaban or warfarin during the period January 2016 to April 2018. Median (range) PCC dose was 2000 units (1000-4500). Intracranial haemorrhage (ICH) was the most common indication (137/344, 39·8%) for PCC use followed by gastrointestinal bleeding (93/344, 27%). ICH patients more frequently received rivaroxaban (62·5%) or apixaban (52·5%) compared to warfarin (34·5%), P = 0·002; and visceral bleeding patients received warfarin more frequently (24·2%) than rivaroxaban (5%) or apixaban (10%), P = 0·003. Median rivaroxaban and apixaban levels were 230 ng/ml (47-759) and 159 ng/ml (45-255). Median International Normalised Ratio pre- and post-PCC in patients on warfarin were 3·4 (1·9-15·4) and 1·2 (1·0-1·9). Blood products use was the same between groups. Thirty-day mortality and re-bleeding rates in patients with ICH were 35% (P = 0·50) and 18% (P = 0·90) with no differences between the groups. Thrombosis occurred in 4·1% patients within 30 days with no difference between groups. Two of 91 (2·2%) patients with ICH only (both on warfarin) had ischaemic strokes within 30 days post-PCC. In conclusion, there was no difference in the safety (thrombosis) or efficacy (30-day mortality, re-bleeding) in use of PCC for MBE in patients on warfarin, rivaroxaban or apixaban.

Topics: Aged; Aged, 80 and over; Blood Coagulation Factors; Disease-Free Survival; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Survival Rate; Warfarin

The correlation between direct oral anticoagulants (DOACs) or Vitamin K Antagonist (VKAs) intake and the incidence of intracranial complications after minor head injury (MHI) is still object of debate: preliminary observation seems to demonstrate lower incidence in intracranial bleeding complications (ICH) in patients taking DOACs than VKA. METHODS. This prospective and observational study was performed to clarify the incidence of ICH in patients in DOACs compared to VKAs. Between January 2016 and April 2018 we have recorded in our ED patients with MHI taking oral anticoagulants. Their hemorragic risk score was calculated and recorded for each patient (Has Bled, Atria and Orbit). RESULTS A total of 402 patients with MHI taking anticoagulant were collected: 226 were receiving one of the four DOACs (dabigatran, rivaroxaban, apixaban or edoxaban) while 176 patients were in therapy with VKA. The rate of intracranial complications was significantly lower in patients receiving DOACs than in patients treated with VKA (p < 0.01). In the VKA group two patients died because of intracranial bleeding. No deaths were recorded in the DOACs group. DISCUSSION patients with MHI who take DOACs have a significant lower incidence of intracranial bleeding complications than those treated with vitamin k antagonists. This statement is supported by the observation that the hemorrhagic risk, measured according to the chosen scores, was similar between the two groups.

Topics: Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Dabigatran; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Risk; Rivaroxaban; Thiazoles; Vitamin K; Warfarin

Intracranial hemorrhage (ICH) is a devastating complication of oral anticoagulation. The aim of this study was to describe the spectrum of ICH and to evaluate the association of warfarin control with the risk of ICH in a nationwide cohort of unselected atrial fibrillation (AF) patients. Methods and Results: The FinWAF is a retrospective registry-linkage study. Data were collected from several nationwide Finnish health-care registers and laboratory databases. The primary outcome was any ICH (traumatic or non-traumatic). The quality of warfarin therapy was assessed continuously by calculating the time in therapeutic range in a 60-day window (TTR60). Adjusted Cox proportional hazard models were used. A total of 53,953 patients were included (53% men; mean age, 73 years; mean follow-up, 2.94 years; mean TTR, 63%). In 129,684 patient-years, 1,196 patients had ICH (non-traumatic, 53.5%; traumatic, 43.6%; traumatic subdural, 38.6%); crude annual rate, 0.92%; 95% CI: 0.87-0.98). A lower TTR60 was significantly associated with higher risk of ICH (TTR60 ≤40% vs. TTR60 >80%; adjusted hazard ratio, 2.16; 95% CI: 1.83-2.54). Other variables independently associated with ICH included age >65 years, previous stroke, male sex, low hemoglobin, thrombocytopenia, elevated alanine aminotransferase, and previous bleeding other than ICH.. Poor control of warfarin treatment was associated with elevated risk of ICH. Approximately half of the ICH were traumatic, mainly subdural.

Topics: Aged; Atrial Fibrillation; Female; Finland; Humans; Intracranial Hemorrhages; Male; Registries; Retrospective Studies; Risk Factors; Warfarin

Background and Purpose- Recurrent bleeding associated with oral anticoagulants (OACs) causes a dilemma in patients with atrial fibrillation (AF) sustaining an intracerebral hemorrhage. Treatment recommendations guiding clinical practice on optimal OAC agent selection in this population are lacking. This study aimed to investigate the comparative effectiveness and safety of non-vitamin K antagonist OAC (NOAC) versus warfarin in patients with AF sustaining an intracerebral hemorrhage. Methods- We conducted a nationwide observational cohort study including patients with AF sustaining an intracerebral hemorrhage and who subsequently claimed an OAC prescription. Contrasts of 1-year risks for ischemic stroke and intracerebral hemorrhage risks were obtained and evaluated by inverse probability treatment weighted absolute risk reduction and risk ratios. Results- Among 622 AF patients with intracerebral hemorrhage, 274 claimed a warfarin prescription and 348 a NOAC prescription. Mean age was 76 years (39% females); 72% had an index nonsevere event and 28% moderate to severe index event according to the Scandinavian Stroke Severity scale. The 1-year ischemic stroke risk was 7.85% for warfarin and 4.01% for NOACs, with a weighted absolute risk reduction of 3.78% (95% CI, -0.15% to 7.71%); the weighted risk ratio was 0.52 (0.27-1.00). For recurrent intracerebral hemorrhage, the risk was 7.00% for warfarin and 5.07% for NOACs. The absolute risk reduction was 1.93% (-2.02% to 5.87%), with an a weighted risk ratio of 0.72 (0.38-1.38). Conclusions- NOACs were associated with a nonsignificant lower risk of ischemic stroke and recurrent intracerebral hemorrhage compared with warfarin. The results add to current recommendations of selecting a NOAC agent for stroke prophylaxis treatment in patients with AF, including those with sustaining an intracerebral hemorrhage.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Female; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Risk; Severity of Illness Index; Stroke; Treatment Outcome; Warfarin

Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months.. This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups.. The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs.. This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Incidence; Intracranial Hemorrhages; Japan; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Prospective Studies; Recurrence; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Patients with cerebral microbleeds have increased risk of intracranial hemorrhage and ischemic stroke. No trial specifically informs antithrombotic therapy for patients with cerebral microbleeds and atrial fibrillation. We investigated the safety of anticoagulation versus no anticoagulation with regard to cerebrovascular outcomes and mortality.. All consecutive atrial fibrillation patients from 2015 to 2018 with MRI evidence of ≥1 cerebral microbleed at time of imaging were reviewed. Patients were treated with warfarin, direct oral anticoagulants, or neither. Primary outcome was all-cause mortality informed by National Death Registry and the composite of ischemic and hemorrhagic stroke. All statistical tests were 2-sided and significant at P < .05.. The median interval from patient identification until the end of electronic health record surveillance was 9.93 months (interquartile range, 2.83-19.17 months). We identified 308 atrial fibrillation patients with cerebral microbleeds; 128(41.6%) were on warfarin, 88(28.6%) on direct oral anticoagulants, and 92(29.9%) on neither. Over the surveillance interval, 87 deaths, 51 ischemic strokes, and 14 hemorrhagic strokes occurred. The estimated likelihoods of the composite stroke outcome and ischemic stroke only did not differ significantly among the 3 groups. However, patients taking direct oral anticoagulants had a significantly smaller likelihood of all-cause mortality than patients who were not anticoagulated (adjusted hazard ratio: .44[.23, .83], P=.012).. In patients with coprevalent atrial fibrillation and cerebral microbleeds, we did not detect differences in subsequent ischemic stroke, hemorrhagic stroke, or both, comparing warfarin, direct oral anticoagulants, or neither. Patients treated with direct oral anticoagulants had better survival than nonanticoagulated patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Clinical Decision-Making; Electronic Health Records; Female; Florida; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Middle Aged; Prevalence; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

Prescribers' concern regarding falls resulting in intracranial hemorrhage is often cited as a justification for under-utilization of oral anticoagulation. We evaluated the safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls. Using MarketScan claims from 11/2012-3/2017, we identified adult, oral anticoagulation-naïve, new-initiators of oral factor Xa inhibitors or warfarin with nonvalvular atrial fibrillation, ≥ 12 months of insurance coverage prior to starting oral anticoagulation and a predicted 2-year risk of falls ≥ 15%. Differences in baseline covariates between cohorts were balanced using inverse probability-of-treatment weights based on propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for intracranial hemorrhage and stroke or systemic embolism were estimated. Among 25,144 nonvalvular atrial fibrillation patients at high-risk for falls (observed fall rate = 11.8%/person-year), oral factor Xa inhibitor use was associated with a 43% (95% CI = 5-65%) reduced hazard of intracranial hemorrhage compared to warfarin. Oral factor Xa inhibitors did not significantly reduce the hazard of stroke or systemic embolism versus warfarin (HR = 0.86, 95% CI = 0.66-1.11). Findings for the intracranial hemorrhage and stroke or systemic embolism endpoints were similar when apixaban and rivaroxaban were evaluated separately versus warfarin (p-interaction ≥ 0.64 for all). Oral factor Xa inhibitors reduced patients' risk of intracranial hemorrhage and were at least as effective in preventing stroke or systemic embolism as warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.

Topics: Accidental Falls; Aged; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Stroke; Treatment Outcome; Warfarin

Warfarin-associated intracranial hemorrhage(w-ICH)usually increases and results in unfavorable outcomes. Administration of prothrombin complex concentrate(PCC)can reverse anticoagulation and correct prothrombin time-international normalized ratio(PT-INR)immediately; it is recommended by some guidelines for cases of w-ICH. We assessed the effect of PCC on blood coagulation.. We administered PCC and vitamin K to 11 patients with w-ICH who were admitted to our hospital between October 2016 and November 2017. We measured the PT-INR at baseline and immediately, 1 hour, 6 hours, and on the day after PCC administration.. Patients' mean(range)PT-INR normalized from 1.92(1.64-3.26)to 1.08(1.03-1.29)immediately after receiving PCC. Patients' PT-INR was 1.17(1.08-1.29)1 hour after receiving PCC, 1.22(1.16-1.52)6 hours after receiving PCC, and 1.17(1.05-1.29)on the day after receiving PCC. In all the cases, no side effects emerged. Five patients had a safe operation. All the patients' modified Rankin Scale scores at discharge were stable or within a permissive limit in comparison with the symptoms on admission.. In our cases, administration of PCC corrected the PT-INR immediately and contributed to a better outcome of w-ICH.

Topics: Anticoagulants; Blood Coagulation Factors; Humans; Intracranial Hemorrhages; Retrospective Studies; Warfarin

Background and Purpose- In the daily practice, low-dose nonvitamin K antagonist oral anticoagulants are commonly used among Asian patients with atrial fibrillation (AF). The aim of the present study was to compare the risks of ischemic stroke, intracranial hemorrhage, and net clinical benefit of Asian patients with AF treated with off-label low-dose and on-label dosing rivaroxaban. Methods- A total of 2214 patients with AF aged ≥20 years treated with rivaroxaban at a tertiary medical center in Taiwan were studied. Patients were categorized into 2 groups: (1) on-label dose (n=1630): ROCKET-AF or J-ROCKET dosage criteria; and (2) off-label low-dose (10 mg/d for patients with an estimated glomerulus filtration rate >50 mL/min, n=584). The risks of ischemic stroke and intracranial hemorrhage were compared between 2 groups. Results- Compared with the on-label dose group, off-label low-dose rivaroxaban was associated with an increased risk of ischemic stroke with an adjusted hazard ratio of 2.75; 95% CI =1.62-4.69; P<0.001). The risk intracranial hemorrhage did not differ significantly between the on-label and off-label low-dosing groups (adjusted hazard ratio =0.62; 95% CI =0.32-1.20; P=0.213). Compared with off-label low-dose group, on-label dosing rivaroxaban was associated with a positive net clinical benefit in different weighted models. The results were consistent among the propensity-matched cohort. Conclusions- Off-label low-dosing rivaroxaban should be avoided for Asian patients with AF giving the higher risk of ischemic stroke without risk reduction in intracranial hemorrhage compared with on-label dosing.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Factors; Rivaroxaban; Stroke; Warfarin

Background and Purpose- Hypertrophic cardiomyopathy patients with atrial fibrillation are at increased risk of stroke, and anticoagulation is strongly recommended. However, limited data are available regarding the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) for primary prevention of stroke. Methods- Using the Korean Health Insurance Review and Assessment Service database, we identified 2397 patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation on oral anticoagulation from 2013 to 2016 without history of ischemic stroke, intracranial hemorrhage (ICH), or gastrointestinal bleeding (992 on warfarin and 1405 on NOACs). Inverse probability of treatment weighting with propensity scores was used to balance covariates between treatment groups. Risk for ischemic stroke, ICH, gastrointestinal bleeding, death, and their composite outcome associated with NOAC use was assessed with warfarin use as the reference. Results- During a mean follow-up of 1.6 years, the incidence rates of ischemic stroke, ICH, gastrointestinal bleeding, death, and composite outcome were all significantly lower in the NOAC than in the warfarin group (stroke, 2.8 versus 5.0; ICH, 0.5 versus 1.3; gastrointestinal bleeding, 2.3 versus 3.0; death, 3.0 versus 5.1; composite, 7.5 versus 12.5 events per 100 person-years). NOACs were associated with significantly lower risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.32-0.68), ICH (HR, 0.31; 95% CI, 0.14-0.69), gastrointestinal bleeding (HR, 0.62; 95% CI, 0.40-0.96), death (HR, 0.45; 95% CI, 0.31-0.65), and the composite outcome (HR, 0.48; 95% CI, 0.38-0.61) than warfarin. The same trend was observed regardless of the NOAC dose and across various high-risk subgroups. In analysis of individual NOACs, all NOACs were associated with lower risks of ischemic stroke and composite outcome. Conclusions- NOACs showed superior effectiveness and safety versus warfarin in the primary prevention of stroke versus warfarin in real-world Asian hypertrophic cardiomyopathy with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Primary Prevention; Stroke; Treatment Outcome; Warfarin

Four-factor prothrombin complex concentrates (PCC) produce a more rapid and complete INR correction compared with 3-factor PCC in patients receiving warfarin. It is unknown if this improves clinical outcomes in the setting of intracranial hemorrhage (ICH).. This multicenter, retrospective cohort study included patients presenting with warfarin-associated ICH reversed with either 4- or 3-factor PCC. The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, discharge location, intensive care unit (ICU) and hospital-free days, INR reversal, and thromboembolic (TE) events at 90 days. Each was analyzed using regression analysis. Continuous and binary outcomes were analyzed using linear and logistic regression, respectively, while ordinal regression was used for discharge location.. Of the 103 patients, 63 received 4-factor PCC. Median age was 79 years [interquartile intervals(IQI 73-84)], median presenting INR was 2.7 (2.2-3.3), and presenting ICH was intraparenchymal in 51% of patients. In-hospital and 30-day mortality were 25 and 35%, respectively. In-hospital mortality was greater among those who received 4-factor PCC, yet was not statistically significant (OR 2.2, 95% CI 0.59-9.4, p = 0.26), as having Glasgow Coma Scale (GCS) ≤8 explained most of the difference (OR 48, 95% CI 14-219, p <0.001). The effect of 4-factor PCC was not statistically significant in any of the secondary analyses. Crude rates of TE events were higher in the 4-factor PCC group (19 vs. 10%), though not significantly.. In-hospital mortality was not improved with the use of 4- versus 3-factor PCC in the emergent reversal of warfarin-associated ICH. Secondary clinical outcomes were similarly nonsignificant.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Emergency Medical Services; Female; Hospital Mortality; Humans; Intracranial Hemorrhages; Male; Outcome Assessment, Health Care; Retrospective Studies; Warfarin

Topics: Anticoagulants; Brain Infarction; Delivery of Health Care; Heparin, Low-Molecular-Weight; Humans; Intracranial Hemorrhages; Neurologists; Practice Patterns, Physicians'; Sinus Thrombosis, Intracranial; State Medicine; Surveys and Questionnaires; United Kingdom; Warfarin

The issue of anticoagulation in individuals with nonvalvular atrial fibrillation (NVAF) and 1 non-gender-related (NGR) risk factor is subject to debate. The reported risk of stroke in untreated individuals is not uniform, and the rate of hemorrhage associated with anticoagulation in this group of individuals is not well defined. To this end, we assessed the rate of stroke and major hemorrhage in individuals treated with warfarin.. individuals were extracted from the START register, an observational, multicenter, dynamic inception cohort study that collects data on NVAF individuals starting anticoagulation therapy. Risk of stroke is stratified using the CHA. Overall, 431 individuals with 1 NGR risk factor were followed up for 604 person-years. One nonfatal ischemic stroke was recorded (0.17 per 100 person-years) during follow-up. On the other hand, there were 9 major bleeding events (1.49 per 100 person-years), with 4 being intracranial hemorrhage (0.66 per 100 person-years), 1 of which was fatal. No difference in patient characteristics, bleeding risk factors, and quality of treatment were found between individuals who bled versus those who did not. However, a trend toward more bleeding events was observed in individuals <65 years old.. We found an elevated risk of major bleeding and intracranial hemorrhage in NVAF individuals treated with warfarin with 1 NGR risk factor for stroke. These data call for caution when treating with warfarin these individuals.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Decision Support Techniques; Drug Prescriptions; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Predictive Value of Tests; Registries; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

Reversal of therapeutic anticoagulation prior to emergency neurosurgical procedures is required in the setting of intracranial hemorrhage. Multifactor prothrombin complex concentrate (PCC) promises rapid efficacy but may increase the probability of thrombotic complications compared to fresh frozen plasma (FFP).. To compare the rate of thrombotic complications in patients treated with PCC or FFP to reverse therapeutic anticoagulation prior to emergency neurosurgical procedures in the setting of intracranial hemorrhage at a level I trauma center.. Sixty-three consecutive patients on warfarin therapy presenting with intracranial hemorrhage who received anticoagulation reversal prior to emergency neurosurgical procedures were retrospectively identified between 2007 and 2016. They were divided into 2 cohorts based on reversal agent, either PCC (n = 28) or FFP (n = 35). The thrombotic complications rates within 72 h of reversal were compared using the χ2 test. A multivariate propensity score matching analysis was used to limit the threat to interval validity from selection bias arising from differences in demographics, laboratory values, history, and clinical status.. Thrombotic complications were uncommon in this neurosurgical population, occurring in 1.59% (1/63) of treated patients. There was no significant difference in the thrombotic complication rate between groups, 3.57% (1/28; PCC group) vs 0% (0/35; FFP group). Propensity score matching analysis validated this finding after controlling for any selection bias.. In this limited sample, thrombotic complication rates were similar between use of PCC and FFP for anticoagulation reversal in the management of intracranial hemorrhage prior to emergency neurosurgical procedures.

Topics: Aged; Anticoagulants; Blood Coagulation Factors; Female; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Propensity Score; Retrospective Studies; Thromboembolism; Trauma Centers; Warfarin

To determine the effect of direct oral anticoagulants (DOACs) compared with warfarin on the 30-day readmission rates in patients with traumatic intracranial hemorrhage (ICH).. We conducted a retrospective review of patients from our hospital's trauma database admitted between June 2011 and October 2015 to our level II trauma center after sustaining a traumatic ICH while receiving anticoagulant therapy. Patients were stratified based on the anticoagulation drug (DOAC or warfarin) prescribed on admission. The readmission rates between the 2 groups were compared using χ. Over the 4-year period, 160 patients were admitted with traumatic ICH. Seventy-nine were receiving warfarin and 57 were receiving a DOAC at admission. Data collected included age, sex, injury severity score, admission Glasgow Coma Score, Abbreviated Injury Scale (head), mechanism of injury, hospital and intensive care unit lengths of stay, discharge destination (eg, home, rehabilitation facility, nursing facility), comorbidities, operative interventions, readmissions, and reasons for the readmissions. The rate of readmission for rebleeding of ICH was significantly lower in the DOAC group compared with the warfarin group (5.3% vs. 17.7%; P = 0.04). Multivariate logistic regression suggests that warfarin use, but not DOAC use, is associated with increased readmission both for all causes and for ICH rebleeding.. Warfarin use is associated with higher readmission rates in patients with intracranial bleeding for both all-cause readmissions and for intracranial rebleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Comorbidity; Female; Humans; Intracranial Hemorrhages; Logistic Models; Male; Multivariate Analysis; Patient Readmission; Recurrence; Retrospective Studies; Treatment Outcome; Warfarin

Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

Topics: American Heart Association; Amyloid; Anticoagulants; Cerebral Small Vessel Diseases; Clinical Decision-Making; Expert Testimony; Humans; Intracranial Hemorrhages; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; United States; Vitamin K; Warfarin

Topics: Administration, Intravenous; Aged; Anticoagulants; Atrial Fibrillation; Brain; Emergency Service, Hospital; Factor V; Factor Xa; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Paresis; Plasma; Tomography, X-Ray Computed; Vitamin K; Warfarin

The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance.. In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of 36 173 rivaroxaban and 79 520 warfarin initiators were variable-ratio matched within 2 monitoring periods.. Statistically significant signals were observed for ischemic stroke (IS) (first period) and intracranial hemorrhage (ICH) (second period) favoring rivaroxaban, and gastrointestinal bleeding (GIB) (second period) favoring warfarin. In follow-up analyses using primary position diagnoses from inpatient encounters for increased definition specificity, the hazard ratios (HR) for rivaroxaban vs warfarin new users were 0.61 (0.47, 0.79) for IS, 1.47 (1.29, 1.67) for GIB, and 0.71 (0.50, 1.01) for ICH. For GIB, the HR varied by age: <66 HR = 0.88 (0.60, 1.30) and 66+ HR = 1.49 (1.30, 1.71).. This study demonstrates the capability of Sentinel to conduct prospective safety monitoring and raises no new concerns about rivaroxaban safety.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Atrial Fibrillation; Brain Infarction; Factor Xa Inhibitors; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pilot Projects; Prospective Studies; Rivaroxaban; United States; United States Food and Drug Administration; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Renal Insufficiency, Chronic; Stroke; Warfarin

The objective of this study is to evaluate the effectiveness of different rivaroxaban dosage regimens in preventing ischemic stroke and systemic thromboembolism among Asians. A retrospective cohort study was conducted on data from nationwide insurance claims in Taiwan. Patients with non-valvular atrial fibrillation under warfarin or rivaroxaban therapy were included. Propensity score matching was used to balance the covariates, and Cox-proportional hazard models were applied to compare the effectiveness and safety of each treatment group. Rivaroxaban was associated with a significantly lower risk of venous thromboembolism (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.29-0.92, P = 0.02) and intracranial hemorrhage (HR: 0.48; 95% CI: 0.32-0.72, P < 0.001) than warfarin. Rivaroxaban 20 mg and 15 mg were associated with a significantly lower risk of ischemic stroke (20 mg, HR: 0.48; CI: 0.29-0.80, P = 0.005; 15 mg, HR: 0.69; CI: 0.53-0.90, P = 0.005), but rivaroxaban 10 mg was not. In the subgroup analysis of patients older than 65 years, the results were generally the same, except that rivaroxaban had a significantly lower risk of ischemic stroke than warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Intracranial Hemorrhages; Male; Retrospective Studies; Rivaroxaban; Stroke; Taiwan; Treatment Outcome; Venous Thromboembolism; Warfarin

Stroke prevention with oral anticoagulants (OACs) is the cornerstone for the management of atrial fibrillation (AF). However, data about the use of OACs among patients ≥90 years of age are limited. We aimed to investigate the risk of ischemic stroke and intracranial hemorrhage (ICH) and the net clinical benefit of OAC treatment for very elderly patients with AF (≥90 years of age).. This study used the National Health Insurance Research Database in Taiwan. Risks of ischemic stroke and ICH were compared between 11 064 and 14 658 patients with and without AF ≥90 years of age without antithrombotic therapy from 1996 to 2011. Patients with AF (n=15 756) were divided into 3 groups (no treatment, antiplatelet agents, and warfarin), and the risks of stroke and ICH were analyzed. The risks of ischemic stroke and ICH were further compared between patients treated with warfarin and nonvitamin K antagonist OACs (NOACs) from 2012 to 2015 when NOACs were available in Taiwan.. Compared with patients without AF, patients with AF had an increased risk of ischemic stroke (event number/patient number, incidence = 742/11 064, 5.75%/y versus 1399/14 658, 3.00%/y; hazard ratio, 1.93; 95% confidence interval, 1.74-2.14) and similar risk of ICH (131/11 064, 0.97%/y versus 206/14 658, 0.54%/y; hazard ratio, 0.85; 95% confidence interval, 0.66-1.09) in competing risk analysis for mortality. Among patients with AF, warfarin use was associated with a lower stroke risk (39/617, 3.83%/y versus 742/11 064, 5.75%/y; hazard ratio, 0.69; 95% confidence interval, 0.49-0.96 in a competing risk model), with no difference in ICH risk compared with nontreatment. When compared with no antithrombotic therapy or antiplatelet drugs, warfarin was associated with a positive net clinical benefit. These findings persisted in propensity-matched analyses. Compared with warfarin, NOACs were associated with a lower risk of ICH (4/978, 0.42%/y versus 19/768, 1.63%/y; hazard ratio, 0.32; 95% confidence interval, 0.10-0.97 in a competing risk model), with no difference in risk of ischemic stroke.. Among patients with AF ≥90 years of age, warfarin was associated with a lower risk of ischemic stroke and positive net clinical benefit. Compared with warfarin, NOACs were associated with a lower risk of ICH. Thus, OACs may still be considered as thromboprophylaxis for elderly patients, with NOACs being the more favorable choice.

Topics: Administration, Oral; Age Factors; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Clinical Decision-Making; Databases, Factual; Female; Fibrinolytic Agents; Humans; Incidence; Intracranial Hemorrhages; Male; Patient Selection; Platelet Aggregation Inhibitors; Propensity Score; Risk Assessment; Risk Factors; Stroke; Taiwan; Time Factors; Treatment Outcome; Warfarin

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

Topics: Aged; Anticoagulants; Drug Interactions; Female; Finland; Gastrointestinal Hemorrhage; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Factors; Simvastatin; Thromboembolism; Treatment Outcome; Warfarin

Different strategies exist for dosing four-factor prothrombin complex concentrate (PCC4) for international normalized ratio (INR) reversal in the setting of life-threatening bleeding. Fixed doses ranging from 1000 IU to 1750 IU have demonstrated efficacy similar to weight-based dosing, however, few studies look exclusively at intracranial hemorrhage (ICH).. Our aim was to evaluate whether a fixed dose of 1000 IU of PCC4 achieves INR reversal similar to weight-based dosing in patients with ICH who were anticoagulated with warfarin.. We compared a weight-based dose vs. 1000 IU PCC4 between January 2014 and January 2017. The primary end point was achieving an INR < 1.5. Secondary end points included in-hospital mortality, patient disposition, and reversal defined by INR < 1.6.. A total of 31 patients were included in the weight-based group and 30 were included in the fixed-dose group, with baseline INRs of 2.98 and 2.84, respectively (p = 0.39). Twenty-two patients (71%) achieved an INR < 1.5 in the weight-based group vs. 16 (53%) in the fixed-dose group (p = 0.15), while 25 (81%) achieved an INR < 1.6 in the weight-based group vs. 22 (73%) in the fixed-dose group (p = 0.49). There was no difference in the number of patients discharged to home (19% vs. 20%; p = 0.95) or in-hospital mortality (26% vs. 27%; p = 0.93).. We found a non-statistically significant difference in warfarin reversal to an INR goal of < 1.5 when comparing a fixed dose of 1000 IU PCC4 and a weight-based dose for ICH. Further studies correlating clinical outcomes with INR reversal are needed.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Cohort Studies; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Retrospective Studies; Warfarin

To determine the likelihood that head injured patients on Warfarin with a negative initial head CT will have a positive repeat head CT. A retrospective chart review of our institution's trauma registry was performed for all patients admitted for blunt head trauma and on Warfarin anti-coagulation from January 2009 to April 2014. Inclusion criteria included patients over 18 years of age with initial GCS ≥ 13, INR greater than 1.5 and negative initial head CT. Initial CT findings, repeat CT findings and INR were recorded. Interventions performed on patients with a delayed bleed were also investigated.. 394 patients met the study inclusion criteria. 121 (31%) of these patients did not receive a second CT while 273 patients (69%) underwent a second CT. The mean INR was 2.74. Six patients developed a delayed bleed, of which two were clinically significant. No patients had any neurosurgical intervention. Our results demonstrate a low rate of delayed bleeding. The utility of repeat head CT in the neurologically stable patient is thus questioned. Patients who have an abnormal baseline neurological status and those with INR >3 may represent a subgroup of patients in whom repeat head CT should be performed.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Head Injuries, Closed; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Time Factors; Tomography, X-Ray Computed; Warfarin; Young Adult

Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality.. Data are collected prospectively on all patients with LVADs implanted at Brigham and Women's Hospital. We added retrospectively collected clinical data for these analyses.. From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93-515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2-3.5) and all received aspirin (81-325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14-7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99-40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34-11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13-8.85).. Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic stroke. Although any stroke increases mortality, post-LVAD hemorrhagic stroke was associated with higher mortality compared with ischemic stroke.

Topics: Aged; Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Female; Heart Failure; Heart-Assist Devices; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Quality of Life; Retrospective Studies; Risk Factors; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Cohort Studies; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Stroke; Warfarin

A target international normalized ratio (INR) of 2-3 has been recommended for patients with atrial fibrillation (AF) and risk factors for thromboembolism. This recommendation is largely based on evidence from observational studies a decade ago. This study utilized collective data from modern trials with warfarin controls to examine the relationship of warfarin anticoagulation, as assessed by INR, on the clinical outcome events of interest.. Data on warfarin-treated patients from three clinical studies supporting the approval of dabigatran (Pradaxa), apixaban (Eliquis), and edoxaban (Savaysa) were pooled. Ischemic stroke, intracranial hemorrhage (ICH), and all-cause death were selected as the outcome events of interest. Multivariate Cox regression modeling was performed to examine the association between time-dependent INR and each outcome event. Benefit-risk assessment was evaluated by summing the estimated annual event rate for ischemic stroke and ICH.. A total of 21,883 patients representing 322 ischemic strokes, 288 ICHs, and 657 all-cause deaths were included in the analysis. The models used suggest that the risk of ischemic stroke is greatly reduced when INR exceeds 2; in contrast, the risk of ICH increases monotonically as INR increases. When combining ischemic stroke and ICH events, the lowest estimated annual event rate was observed between INR of 2 and 2.5; the risk only slightly increased between INR of 1.8 and 3.0. Similarly, a U-shaped relationship between INR and the risk of all-cause death was found.. This study using collective warfarin data from recent large prospective trials indicates that INR between 2 and 2.5 provides the best balance between ischemic stroke and ICH, as well as optimal protection against death in patients with AF.

Topics: Aged; Atrial Fibrillation; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Randomized Controlled Trials as Topic; Stroke; United States; Warfarin

Background and Purpose- Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE. Nontraumatic intracranial hemorrhage (ICH) is one of the most devastating potential complications of anticoagulation therapy. We sought to compare the rates of ICH in patients treated with DOACs versus those treated with warfarin for DVT/PE. Methods- The MarketScan Commercial Claims and Medicare Supplemental databases were used. Adult DVT/PE patients without known atrial fibrillation and with prescriptions for either a DOAC or warfarin were followed for the occurrence of inpatient admission for ICH. Coarsened exact matching was used to balance the treatment cohorts. Cox proportional-hazards regressions and Kaplan-Meier survival curves were used to estimate the association between DOACs and the risk of ICH compared with warfarin. Results- The combined cohort of 218 620 patients had a median follow-up of 3.0 months, mean age of 55.4 years, and was 52.1% women. The DOAC cohort had 26 980 patients and 8 ICH events (1.0 cases per 1000 person-years), and the warfarin cohort had 191 640 patients and 324 ICH events (3.3 cases per 1000 person-years; P<0.0001). The DOAC cohort had a lower hazard ratio for ICH compared with warfarin in both the unmatched (hazard ratio=0.26; P=0.0002) and matched (hazard ratio=0.20; P=0.0001) Cox proportional-hazards regressions. Conclusions- DOACs show superior safety to warfarin in terms of risk of ICH in patients with DVT/PE.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Follow-Up Studies; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Venous Thrombosis; Warfarin

Clinical variables including hypertension could be linked with major bleeding events and death beyond vitamin K antagonist (warfarin) or direct oral anti-coagulants (DOACs) treatment strategy.. Subgroup analysis of major bleeding (primary endpoint) associated with clinical variables, site of bleeding, ongoing antithrombotics, reversal treatment or blood transfusion, outcomes (secondary endpoints) was performed in patients with bleeding events submitted to hard 5:1 propensity-score matching for hypertension.. Enrolled patients were 2,792 (mean age, 65.6 ± 19.9 years) during 2-year survey including 166,000 visits, of 200,000 inhabitants catchment area; 8,239 patients received warfarin and 3,797 DOACs. Hypertension account for 1,077 (39%) patients; major bleeding for 474 (17%); death for 29 (1%), and 72 (3%) on 1-month and 1-year, respectively. Hypertension, age, glucose, cancer, ischemic vascular disease, and CHA2D2VASc score were more likely to link with major bleeding. On multivariate analysis, only age (odds ratio [OR], 1.02; P < 0.001), CHA2DS2VASc score ≥ 2 (OR, 2.14; P = 0.001), and glucose (OR, 1.01; P = 0.005) were predictors of major bleeding. Kaplan-Meier analysis demonstrated patients with hypertension as compared with patients without showed 60% versus 20% death on 1-month (P < 0.001). Warfarin compared with DOACs was more likely to present with major bleeding (0.7% versus 0.2%; OR, 2.8; P = 0.005). Receiver operator characteristics analysis showed high value (0.61) of age and glucose over creatinine and systolic arterial pressure (P = NS).. Four in 10 patients with major bleeding showed hypertension; of these 8 in 10 will die within 1 month. Warfarin compared with DOACs was more likely to present with major bleeding.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Blood Glucose; Blood Transfusion; Cardiovascular Diseases; Creatinine; Dabigatran; Emergency Service, Hospital; Epistaxis; Female; Gastrointestinal Hemorrhage; Hematuria; Hemoptysis; Hemorrhage; Humans; Hypertension; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prognosis; Propensity Score; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Severity of Illness Index; Sex Factors; Thiazoles; Warfarin

Intracranial hemorrhage (ICH) is a complication of warfarin-associated anticoagulation resulting in significant morbidity and mortality. The purpose of this study was to assess whether interhospital transfer delays the administration of 4-factor prothrombin complex concentrate to patients with warfarin-associated ICH.. This was a retrospective cohort study of all patients presenting to a 60,000 visit academic ED between August 2013 and July 2017 requiring emergent anticoagulation reversal for warfarin-associated ICH. Patients were divided into 2 cohorts: (1) transfer patients who arrived at the academic center after receiving care in a local community hospital and (2) control patients who presented directly to the academic center ED. The primary outcome was time to administration of 4-factor prothrombin complex concentrate. Secondary outcomes included hematoma expansion, guideline-adherent vitamin K administration (10mg IV), intensive care unit and hospital length of stay, disposition at discharge, and in-hospital mortality.. This study included 203 patients (177 transfer patients, 26 control). The median time to arrival in transfer patients was 186 minutes (IQR 145-242). The median time to administration of guideline-adherent therapy in transfer patients was 296 minutes, compared to 119 minutes in patients who were not transferred (median difference= -176, 95% confidence interval -143 to -208, P ≤ .001). Delay in anticoagulation reversal did not result in hematoma expansion, intensive care unit and hospital length of stay, discharge disposition, or in-hospital mortality.. Patients requiring interhospital transfer experienced significant delays in guideline-adherent anticoagulation reversal for warfarin-associated ICH, but this delay was not associated with worse outcomes.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Coagulants; Drug Administration Schedule; Female; Guideline Adherence; Hospital Mortality; Hospitals, Community; Humans; Intracranial Hemorrhages; Length of Stay; Male; Patient Discharge; Patient Transfer; Practice Guidelines as Topic; Retrospective Studies; Risk Factors; Time Factors; Time-to-Treatment; Treatment Outcome; Vitamin K; Warfarin

Advancements in the treatment of warfarin-associated intracranial hemorrhage (ICH) include the use of four-factor prothrombin complex concentrate (4F-PCC), which has demonstrated more rapid reversal of the international normalized ratio (INR) when compared with fresh frozen plasma. A pharmacist-driven protocol for 4F-PCC was implemented within our institution, which allows for pharmacist approval of 4F-PCC in patients diagnosed with warfarin-associated ICH and an INR ≥2. The pharmacist is responsible for determining the appropriate dose of 4F-PCC, preparation, bedside delivery, and order entry into the electronic medical record. Prior to implementation of the new protocol, the blood bank was responsible for 4F-PCC approval, dosing, product preparation, and arranging delivery with emergency department (ED) staff. The purpose of this study was to evaluate the impact of a pharmacist-driven protocol on time to 4F-PCC administration in warfarin-associated ICH.. We performed a retrospective review of consecutive patients who received 4F-PCC in a single ED from September 2015 through February 2017. Patients ≥18 years old were eligible for inclusion based on three criteria: confirmed diagnosis of ICH; confirmed warfarin use; and INR ≥2. Secondary outcomes included dose of 4F-PCC in concordance with INR and weight-based dosing recommendations and hospital protocol, as well as concomitant intravenous vitamin K administration.. A total of 48 patients met inclusion criteria for the study with 24 patients in each protocol group. The median time to administration of 4F-PCC in the pharmacist-driven protocol group was 35 minutes (interquartile range [IQR] [25-62]; range, 11-133) compared with 70 minutes (IQR [34-89]; range, 14-244) in the pre-protocol group (p=0.034). We saw no differences for appropriate 4F-PCC dosing based on INR and patient weight between the two groups.. Implementation of a pharmacist-driven protocol for 4F-PCC in the ED at our institution significantly reduced time to administration in patients presenting with warfarin-associated ICH.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Pharmacists; Retrospective Studies; Time Factors; Warfarin

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Background and Purpose- The increased use of novel oral anticoagulants (NOACs) to control atrial fibrillation is largely driven by the assumption that they are equally effective as warfarin at preventing ischemic stroke while putting patients at lower risk of hemorrhages. To test this hypothesis, a retrospective study of the relative incidence of strokes among patients taking NOACs versus those taking warfarin is performed. Methods- Relative stroke incidence in the 2 groups of patients was compared using odds ratios and Fisher exact tests for significance using a data set of 71 365 on NOACs and 59 546 patients on warfarin. In addition, the 7033 patients with a record of both warfarin and NOAC use were analyzed as a separate cohort. Results- There is a significantly higher (odds ratio=1.29, <0.001) frequency of ischemic strokes among patients prescribed NOACs compared with those on warfarin. The relative frequency of ischemic strokes was also higher for every individual NOAC compared with warfarin (these higher frequencies are statistically significant for dabigatran and apixaban, though not for edoxaban and rivaroxaban). There is a lower incidence of intracranial hemorrhages and nontraumatic hemorrhages in general among patients taking NOACs, consistent with the published literature. Comparisons of the demographic and clinical profiles of the patients taking NOACs to those on warfarin do not show significantly higher background stroke risk in NOAC patients; in fact, patients on NOACs tend to be at lower background risk overall for ischemic strokes. Conclusions- Because NOAC use is associated with higher ischemic stroke risk together with a lower risk of hemorrhages than warfarin use, it can be concluded that patients on warfarin are more strongly anticoagulated. The observed effect could be a secondary consequence of dosage control or alternatively a result of different anticoagulant effects among the different medications.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Dabigatran; Female; Humans; Incidence; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Thiazoles; Warfarin

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antithrombins; Dabigatran; Humans; Intracranial Hemorrhages; Stroke; Warfarin

A historical cohort analysis of the Japan medical data center (JMDC) claims databases was performed to compare the incidence rates of bleeding events with warfarin (WF) versus direct oral anticoagulant (DOAC) treatment in patients with non-valvular atrial fibrillation. The aim of this study is to clarify the risk factors for bleeding events in younger patients newly treated with WF or DOAC in clinical practice setting. Patients who newly initiated WF or DOAC treatment from April 2012 to March 2015 were selected from the JMDC claims database. A 1:1 propensity score matching analysis was used for new users of WF or DOAC. Kaplan-Meier curves were generated to depict the time to bleeding event (total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage) during the follow-up period. Cox proportional regression models were used to estimate the hazard ratios for total bleeding events caused by oral anticoagulants. Overall, 2,046 patients (503 WF and 1,543 DOAC) were included. After applying propensity score matching, Kaplan-Meier analysis of the WF and DOAC groups displayed comparable incidences of total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage. Cox proportional hazards modeling showed that the use of WF was not associated with total bleeding events compared with DOAC (hazard ratio: 1.21, 95% confidence interval: 0.93-1.54,

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Child; Child, Preschool; Databases, Factual; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Infant; Infant, Newborn; Intracranial Hemorrhages; Japan; Male; Middle Aged; Time Factors; Warfarin; Young Adult

Oral anticoagulants (OACs) effectively reduce the risk of stroke in atrial fibrillation (AF). Three non-vitamin K antagonist OACs (NOACs) are introduced in regular care based on promising results compared with warfarin in randomized trials. This study compares outcomes with NOAC vs. warfarin treatment in OAC naïve AF patients in routine care, including primary care, in a large region with decentralized anticoagulant treatment.. Population-based cohort study. Individuals with non-valvular AF who initiated treatment with NOAC (n = 9279) or warfarin (n = 12 919) from 2012 to 2015 were identified in the Stockholm administrative health data register (population 2.2 million). Adjusted Cox regression analyses were performed to evaluate TIA/ischaemic or unspecified stroke/death, and severe bleeds (co-primary endpoints); and secondarily for components of the composites. NOAC patients were younger (72.9 vs. 74.1 years) and had lower CHA2DS2VASc scores (3.42 vs. 3.68) than warfarin patients. NOAC vs. warfarin treatment was associated with similar risks for TIA/ischaemic or unspecified stroke/death [hazard ratio (HR) 0.94; 0.85-1.05] and severe bleeds (HR 1.02; 0.88-1.19); lower risks of intracranial bleeds (HR 0.72; 0.53-0.97) or haemorrhagic stroke (HR 0.56; 0.34-0.93), but a higher risk for gastrointestinal bleeds (HR 1.28; 1.04-1.59). The advantages with NOAC treatment were most pronounced with standard dose in patients below 80 years, and with dose reduction in patients aged 80 and above.. This population-based cohort study of routine care indicates similar or better effectiveness and safety with NOAC compared with warfarin treatment. NOACs were associated with fewer intracranial bleeds, but more gastrointestinal bleeds.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Registries; Risk Factors; Stroke; Sweden; Time Factors; Treatment Outcome; Warfarin

The number of anticoagulated trauma patients is increasing. Trauma patients on warfarin have been found to have poor outcomes, particularly after intracranial hemorrhage (ICH). However, the effect of novel oral anticoagulants (NOAs) on trauma outcomes is unknown. We hypothesized that patients on NOAs would have higher rates of ICH, ICH progression, and death compared with patients on traditional anticoagulant and antiplatelet agents.. This was a prospective observational trial across 16 trauma centers. Inclusion criteria was any trauma patient admitted on aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, or apixaban. Demographic data, admission vital signs, mechanism of injury, injury severity scores, laboratory values, and interventions were collected. Outcomes included ICH, progression of ICH, and death.. A total of 1,847 patients were enrolled between July 2013 and June 2015. Mean age was 74.9 years (SD ± 13.8), 46% were female, 77% were non-Hispanic white. At least one comorbidity was reported in 94% of patients. Blunt trauma accounted for 99% of patients, and the median Injury Severity Score was 9 (interquartile range, 4-14). 50% of patients were on antiplatelet agents, 33% on warfarin, 10% on NOAs, and 7% on combination therapy or subcutaneous agents.Patients taking NOAs were not at higher risk for ICH on univariate (24% vs. 31%) or multivariate analysis (incidence rate ratio, 0.78; confidence interval 0.61-1.01, p = 0.05). Compared with all other agents, patients on aspirin (90%, 81 mg; 10%, 325 mg) had the highest rate (35%) and risk (incidence rate ratio, 1.27; confidence interval, 1.13-1.43; p < 0.001) of ICH. Progression of ICH occurred in 17% of patients and was not different between medication groups. Study mortality was 7% and was not significantly different between groups on univariate or multivariate analysis.. Patients on NOAs were not at higher risk for ICH, ICH progression, or death.. Prognostic/epidemiologic study, level III.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Clopidogrel; Dabigatran; Female; Humans; Injury Severity Score; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Ticlopidine; Trauma Centers; Warfarin; Wounds and Injuries; Wounds, Nonpenetrating

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Warfarin

: When patients on anticoagulation present with intracranial bleeding, stopping the bleeding is paramount. Despite the availability of multiple options to reverse anticoagulation, no study has directly compared the effectiveness of the procoagulants recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination, and 4-factor PCC on improving patient outcomes compared with a control. This study examined the medical records of 197 warfarin patients with intracranial hemorrhage, an initial international normalized ratio (INR) greater than 1.5, and who received rFVIIa (26), the combination (84), 4-PCC (50), or no procoagulant, the control group (37). Mortality, length of stay, location discharged, change in INR prior to and postdrug administration, plasma use, and number of thromboembolic complications were used to assess effectiveness. Although INR decreased in all groups (1.31 rFVIIa vs. 2.04 combination vs. 1.41 4-PCC vs. 1.20 control, P = 0.07), the combination group had the greatest percentage to reach an INR of less than 1.3 (46.2 vs. 73.8 vs. 58.0 vs. 43.2%, P = 0.004). The combination and control groups experienced a high, though nonsignificant, number of thromboembolic complications (5.6 vs. 19.0 vs. 7.7 vs. 12.9%, P = 0.533). The rFVIIa group used the most plasma and had the longest length of stay. Mortality did not differ significantly among groups. Although the combination improved INR compared with control, this had a high number of complications. Judicious use of procoagulants is recommended due to their expense and lack of significant improvement in outcomes compared with control.

Topics: Aged; Aged, 80 and over; Blood Coagulation Factors; Case-Control Studies; Drug Therapy, Combination; Factor VIIa; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Length of Stay; Male; Middle Aged; Mortality; Recombinant Proteins; Thromboembolism; Warfarin

Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes.. We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1.6-1.9) in the setting of both traumatic and spontaneous intracranial bleeding.. A total of 21/134 (15.7%) patients with either spontaneous or traumatic intracranial hemorrhage presented with an INR value of 1.6-1.9. Nine patients (43%) presented with traumatic bleeding and 12 (57%) with spontaneous bleeding. The median (IQR) presenting INR was 1.8 (1.7, 1.9) which decreased to 1.3 (1.2, 1.3) following the administration of low-dose 4F-PCC (median dose = 1062 units; 15.2 units/kg). A total of 19/20 (95%) patients achieved a goal INR value of ≤1.5 on the first check following dosing and 17/20 (85%) achieved an INR value ≤1.3. One patient did not have follow-up INR testing due to withdrawal of life support. No patient experienced hematoma expansion within 48 h of 4F-PCC, and there were no thromboembolic events within 72 h of administration.. The administration of low dose (15 units/kg) of 4F-PCC for urgent warfarin reversal in the setting of CNS hemorrhage was effective in correcting the INR in patients presenting with INR values of 1.6-1.9. Further assessment of low-dose PCC for urgent reversal of modest INR elevation is warranted.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Humans; International Normalized Ratio; Intracranial Hemorrhage, Traumatic; Intracranial Hemorrhages; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Warfarin

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Craniocerebral Trauma; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Stroke; Thiazoles; Warfarin

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Vitamin K; Warfarin

The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry.. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models.. Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Renal Dialysis; Republic of Korea; Stroke; Thromboembolism; Warfarin

Topics: Atrial Fibrillation; Brain Ischemia; Humans; Intracranial Hemorrhage, Traumatic; Intracranial Hemorrhages; Stroke; Warfarin

To determine the incidence and severity of bleeding events requiring hospitalization among patients with atrial fibrillation (AF) receiving anticoagulants (dabigatran or warfarin) or antiplatelet agents (eg, aspirin and clopidogrel).. This was a single-center, retrospective cohort study involving 1494 patients with AF hospitalized from November 1, 2010, to November 1, 2011, with prior warfarin, dabigatran, or antiplatelet therapy.. Overall bleeding events in the dabigatran group compared to the warfarin group were 24% and 12%, respectively ( P = .004). Of these events, individually, there were no significant differences in major (56% vs 58%, P = .88), life-threatening (25% vs 36%, P = .38), or minor bleeding (44% vs 42%, P = .06). Gastrointestinal (GI) bleeding occurred more in the dabigatran group compared to the warfarin group ( P = .02). Intracranial bleeding occurred in 15% of patients in the warfarin group and did not occur at all in the dabigatran group. Warfarin patients had significantly more overall bleeding events compared to antiplatelet therapy ( P < .001), with an increasing trend seen in major bleeding ( P = .06). GI bleeding, however, favored the warfarin group over the antiplatelet group (48% vs 73%, P = .04).. Anticoagulation with dabigatran was associated with an overall increased occurrence of bleeding requiring hospital admission compared to warfarin. GI bleeding was more prevalent with dabigatran and antiplatelets than with warfarin. There were more intracranial hemorrhages seen in the warfarin group.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cohort Studies; Dabigatran; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Retrospective Studies; Warfarin

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse.. To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE) and intracranial bleeding in AF.. Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized differences in 1-year absolute risks.. Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient-specific follow-up limited to the first 2 years, 1054 stroke/TE occurred and 261 intracranial bleedings. Standardized absolute risk (95% CI) of stroke/TE at 1 year after initiation of VKA was 2.01% (1.80% to 2.21%). In relation to VKA, the absolute risk differences were for dabigatran 0.11% (-0.16% to 0.42%), rivaroxaban 0.05% (-0.33% to 0.48%), and apixaban 0.45% (-0.001% to 0.93%). For the intracranial bleeding outcome, the standardized absolute risk at 1 year was for VKA 0.60% (0.49% to 0.72%); the corresponding absolute risk differences were for dabigatran -0.34% (-0.47% to - 0.21%), rivaroxaban -0.13% (-0.33% to 0.08%), and apixaban -0.20% (-0.38% to - 0.01%).. Among anticoagulant-naïve AF patients, treatment with NOACs was not associated with significantly lower risk of stroke/TE compared with VKA, but intracranial bleeding risk was significantly lower with dabigatran and apixaban.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Dabigatran; Denmark; Female; Hospitalization; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Stroke; Taiwan; Treatment Outcome; Warfarin

The objective of this study was to study the association between antithrombotic treatment and risk of hemorrhagic stroke (HS) in patients with atrial fibrillation (AF) treated in primary health care.. Study population included all adults (n = 12,215) 45 years and older diagnosed with AF at 75 primary care centers in Sweden 2001-2007. Outcome was defined as a first hospital episode with a discharge episode of HS after the AF diagnosis. Association between HS and persistent treatment with antithrombotic agents (warfarin, acetylsalicylic acid (ASA), clopidogrel) was explored using Cox regression analysis, with hazard ratios (HRs) and 95 % CIs. Adjustment was made for age, socioeconomic status, and co-morbid cardiovascular conditions.. During a mean of 5.8 years (SD 2.4) of follow-up, 162 patients (1.3 %; 67 women and 95 men) with HS were recorded. The adjusted risk associated with persistent warfarin treatment compared to no antithrombotic treatment consistently showed no increased HS risk, HR for women 0.53 (95 % CI 0.23-1.27) and for men 0.55 (95 % CI 0.29-1.04); corresponding HRs for ASA were, for women, 0.45 (95 % CI 0.14-1.44) and, for men, 0.56 (95 % CI 0.24-1.29).. In this clinical setting, we found no evidence pointing to an increased risk of HS with antithrombotic treatment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Primary Health Care; Stroke; Sweden; Ticlopidine; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Intracranial Hemorrhages; Risk Factors; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Intracranial Hemorrhages; Risk Factors; Stroke; Warfarin

The aim of this study was to review and describe the use of Prothrombinex by a physician-led retrieval service based remote from a hospital blood bank.. This is a retrospective observational study. Patients to whom Prothrombinex was administered by the retrieval team were identified from the retrieval service patient database. The paper case cards of the identified patients were then manually reviewed and the data matched to patients in the state-wide electronic laboratory record.. Between 1 January 2010 and 30 November 2013 38 cases were identified. For 28 the indication was warfarinisation associated with life-threatening bleeding (most commonly intracranial or gastrointestinal tract). In the remaining 10 cases, Prothrombinex was used to treat coagulopathy associated with liver disease or massive haemorrhage. The median time saved by the retrieval team administering PTX-VF, rather than waiting to the receiving centre, was 120 min (interquartile range: 85-195 min). The median dose of PTX-VF administered was 23.25 IU/kg (interquartile range: 20-33 IU/kg). Paired international normalised ratios (INRs) were available for 33 of the 38 patients. In the warfarin group, all patients had an improvement in their INR and 21 of 25 had correction of their INR. In the non-warfarin group, the effect on INR was more variable.. Prothrombinex is a clinically useful product that can be relatively easily stored and used by retrieval services, even if they are based in isolation from a hospital blood bank. More research is required to look at the utility of Prothrombinex for non-warfarin-related bleeding in the pre-hospital and retrieval environment.

Topics: Adult; Aged; Anticoagulants; Blood Banks; Blood Coagulation Disorders; Blood Coagulation Factors; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Liver Diseases; Male; Middle Aged; Retrospective Studies; Statistics, Nonparametric; Time-to-Treatment; Warfarin

Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics.. The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use.. Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use.. Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.

Topics: Aged; Anticoagulants; Cohort Studies; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Humans; Hypolipidemic Agents; Incidence; Insurance Benefits; Intracranial Hemorrhages; Male; Medicare; Middle Aged; Propensity Score; United States; Warfarin

The increase in the risk for bleeding associated with antithrombotic therapy causes a dilemma in patients with atrial fibrillation (AF) who sustain an intracranial hemorrhage (ICH). A thrombotic risk is present; however, a risk for serious harm associated with resumption of anticoagulation therapy also exists.. To investigate the prognosis associated with resuming warfarin treatment stratified by the type of ICH (hemorrhagic stroke or traumatic ICH).. This nationwide observational cohort study included patients with AF who sustained an incident ICH event during warfarin treatment from January 1, 1998, through February 28, 2016. Follow-up was completed April 30, 2016. Resumption of warfarin treatment was evaluated after hospital discharge.. No oral anticoagulant treatment or resumption of warfarin treatment, included as a time-dependent exposure.. One-year observed event rates per 100 person-years were calculated, and treatment strategies were compared using time-dependent Cox proportional hazards regression models with adjustment for age, sex, length of hospital stay, comorbidities, and concomitant medication use.. A total of 2415 patients with AF in this cohort (1481 men [61.3%] and 934 women [38.7%]; mean [SD] age, 77.1 years [9.1 years]) sustained an ICH event. Of these events, 1325 were attributable to hemorrhagic stroke and 1090 were secondary to trauma. During the first year, 305 patients with a hemorrhagic stroke (23.0%) died, whereas 210 in the traumatic ICH group (19.3%) died. Among patients with hemorrhagic stroke, resuming warfarin therapy was associated with a lower rate of ischemic stroke or systemic embolism (SE) (adjusted hazard ratio [AHR], 0.49; 95% CI, 0.24-1.02) and an increased rate of recurrent ICH (AHR, 1.31; 95% CI, 0.68-2.50) compared with not resuming warfarin therapy, but these differences did not reach statistical significance. For patients with traumatic ICH, resuming warfarin therapy also was associated with a lower rate of ischemic stroke or SE (AHR, 0.40; 95% CI, 0.15-1.11); however, in contrast to patients with hemorrhagic stroke, therapy resumption was associated with a significantly lower rate of recurrent ICH (AHR, 0.45; 95% CI, 0.26-0.76). A reduction in mortality was associated with resuming warfarin therapy among patients with hemorrhagic stroke (AHR, 0.51; 95% CI, 0.37-0.71) and those with traumatic ICH (AHR, 0.35; 95% CI, 0.23-0.52).. Resumption of warfarin therapy after spontaneous hemorrhagic stroke in patients with AF was associated with a lower rate of ischemic events and a higher rate of recurrent ICH. Among patients with a traumatic ICH, a similar lower rate of ischemic events was found; however, a lower relative risk for recurrent ICH despite resuming warfarin treatment was also revealed.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Denmark; Female; Follow-Up Studies; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Medication Therapy Management; Outcome and Process Assessment, Health Care; Patient Selection; Proportional Hazards Models; Risk Adjustment; Stroke; Time Factors; Warfarin

Not all patients with warfarin-related acute intracranial hemorrhage (ICH) achieve full reversal of international normalized ratio (INR) after the first dose of weight-based prothrombin complex concentrate (PCC). We sought to identify factors associated with anticoagulation reversal failure after the first dose of PCC.. Consecutive patients who were hospitalized with warfarin-related acute ICH at a tertiary center between 1 January 2010 and 31 December 2012 were studied. Anticoagulation reversal failure was defined as INR ≥ 1.5 after the first dose of PCC. Logistic regression was performed to determine the predictors of anticoagulation reversal failure.. Fifty-one patients with acute ICH received PCC for warfarin reversal using a weight-based protocol. Overall, 23 (45%) patients did not achieve full reversal of INR after the first dose. Those with anticoagulation reversal failure were obese (body mass index > 30 kg/m(2)) (41% vs. 14%, p = 0.03), had a higher initial INR (3.0 ± 1.4 vs. 2.0 ± 0.7, p = 0.001), and had a higher prevalence of initial INR >2.0 (22% vs. 67%, p = 0.001), compared with those who were successfully reversed. Multivariable logistic regression identified obesity (odds ratio 7.88, 95% CI 1.12 to 55.68) and initial INR >2.0 (odds ratio 12.49, 95% CI 2.27 to 68.87) as independent predictors of anticoagulation reversal failure.. Obesity and elevated initial INR are independently associated with anticoagulation reversal failure using the weight-based PCC protocol in patients with warfarin-related acute ICH. Further studies are needed to determine more effective dosing protocols and individualized strategies for anticoagulation reversal after acute ICH, especially among obese patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Body Mass Index; Comorbidity; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Models, Biological; Obesity; Retrospective Studies; Risk; Treatment Failure; Warfarin

New oral anticoagulants (NOACs) are now clinically available. However, few studies have demonstrated which patients with non-valvular atrial fibrillation (NVAF) actually receive NOACs in a clinical setting. We analyzed 182 NVAF patients who received oral anticoagulants. Clinical backgrounds and the risk of stroke, systemic embolism, and bleeding associated with oral anticoagulants were investigated. Seventy-three (40 %) patients were treated with NOACs and 109 (60 %) patients were treated with warfarin. A significantly lower mean number of bleeding risk factors was observed among the patients treated with NOACs than among those treated with warfarin (P = 0.010). Of the bleeding risk factors, NOACs were significantly less frequently prescribed in patients with a bleeding history and elderly subjects (>65 years) than in those who received warfarin (P < 0.001 and P = 0.029). A multivariate logistic regression analysis revealed that CHF and bleeding history were independently and significantly associated with the administration of NOACs (P = 0.047 and P = 0.003). The rate of a history of intracranial hemorrhage was comparable between the patients treated with NOACs and those treated with warfarin (P = 1.000). Significantly lower rates of a history of gastrointestinal and other minor bleeding were observed in the patients who received NOACs versus those who received warfarin (P = 0.001 and P = 0.026). NOACs were less frequently prescribed in patients with a history of bleeding, especially those with a history of gastrointestinal bleeding in a clinical setting.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Drug Prescriptions; Drug Utilization Review; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Patient Selection; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

In elderly patients (≥ 75 years), evidence of dabigatran efficacy is lacking and increased vigilance is warranted. We aimed to assess dabigatran effectiveness and safety in elderly patients in real-world practice. We conducted a population-based study using administrative databases, in Quebec (1999-2013). Dabigatran users (110/150 mg) were compared with matched warfarin users with regard to stroke and bleeding events. Age was categorised into < 75 or ≥ 75 years. Propensity score adjusted models were used. The cohort consisted of 15,918 dabigatran users and 47,192 matched warfarin users, with 67.3% being elderly patients. The elderly predominantly used the lower dose (80.1%) while younger patients mainly used the higher dose (80.0%). In multivariable analyses adjusted for propensity score, the risk of stroke in elderly patients using dabigatran, was no different than the risk in warfarin users (HR 1.05, 95% CI: 0.93, 1.19) regardless of dabigatran dose. However, dabigatran was associated with lower rates of intracranial haemorrhage (HR 0.60, 95% CI: 0.47-0.76) and higher rates of gastrointestinal bleeding (HR 1.30 95% CI: 1.14-1.50) when compared to warfarin. Based on real-life experience, dabigatran can offer an alternative to warfarin in elderly patients, with fewer intracranial bleeding events. However, caution is warranted for gastrointestinal bleeding.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Blood Coagulation; Dabigatran; Databases, Factual; Drug Utilization Review; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Multivariate Analysis; Propensity Score; Proportional Hazards Models; Quebec; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

Little is known about the clinical benefit of a non-vitamin K antagonist oral anticoagulant compared with warfarin in elderly Chinese patients with atrial fibrillation (AF).. The purpose of this study was to evaluate the clinical benefit of dabigatran in elderly (age ≥80 years) Chinese patients with nonvalvular AF with regard to the risk of ischemic stroke and intracranial hemorrhage (ICH).. This was an observational study.. We studied 571 Chinese patients (mean age 84.8 ± 4.0 years; 58.1% women) with nonvalvular AF. The primary outcome was hospital admission for ischemic stroke, and the secondary outcome was admission for ICH. The mean CHA2DS2-VASc (congestive heart failure [1 point], hypertension [1 point], age 65-74 years [1 point] and age ≥75 years [2 points], diabetes mellitus [1 point], prior stroke or transient ischemic attack [2 points], vascular disease [1 point], sex category [female] [1 point]) and HAS-BLED (hypertension [1 point], abnormal renal/liver function [1 point], stroke [1 point], bleeding history [1 point] or predisposition [1 point], labile international normalized ratio [1 point], elderly [age >65 years] [1 point], drugs/alcohol concomitantly [1 point]) scores were 4.8 ± 1.6 and 2.4 ± 0.8, respectively. Of 571 patients, 129 (22.6%) were taking dabigatran 110 mg twice daily and the remaining were on warfarin. After a mean follow-up of 2.6 years (a total of 1471 patient-years), ischemic stroke occurred in 83 patients on warfarin (6.9% per year) compared with 4 patients on dabigatran (1.4% per year) (hazard ratio 0.22; 95% confidence interval 0.23-0.67). There were 8 incidences of ICH: 7 in patients on warfarin (0.59% per year) and 1 patient on dabigatran (0.35% per year). Dabigatran was associated with a substantially lower ischemic stroke risk (1.4% per year vs 5.4% per year) and similar ICH risk (0.35% per year vs 0.36% per year) as compared with warfarin with time in therapeutic range (TTR) ≥55%.. In elderly Chinese patients with AF, this study suggested that dabigatran achieved superior stroke risk reduction and similar risk of ICH compared with warfarin with TTR ≥55%. Dabigatran may be preferable to warfarin in elderly patients with AF for stroke prevention, particularly in those with poor TTR.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; China; Dabigatran; Female; Humans; Intracranial Hemorrhages; Male; Outcome Assessment, Health Care; Stroke; Warfarin

Prothrombin complex concentrates (PCCs) are commonly used to rapidly reverse warfarin-associated coagulopathy; however, venous thromboembolism (VTE) is an established adverse event.. To determine risk factors for VTE AFTER administration of a three-factor prothrombin complex concentrate (3F-PCC) for warfarin-associated intracranial hemorrhage (ICH).. Retrospective chart review of all patients with a warfarin-associated ICH who received a 3F-PCC at a single tertiary care hospital between 2008 and 2013. Outcomes were VTE events (defined as deep vein thrombosis [DVT], pulmonary embolism [PE], limb ischemia, transient ischemic attack, cerebrovascular accident, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction, and unexplained sudden death) occurring within 30 days of 3F-PCC administration. Risk factors in subjects with and without VTE complications were compared via Fisher's exact test, Student's t-test, Mann-Whitney U test, and univariate logistic regression as appropriate.. Two hundred nine subjects received 3F-PCC for warfarin-associated ICH. There were 22 VTE events in 19 subjects (9.1%). Baseline characteristics of subjects with and without VTE were similar. There was a significant increase in VTE events in 29 subjects who were taking warfarin for a previous PE or DVT (36.8% vs. 11.6%, p = 0.007; logistic regression odds ratio 4.455, p = 0.005).. Patients with a prior history of PE or DVT who were given 3F-PCC for warfarin-associated ICH were 4.5 times more likely to sustain a VTE within 30 days. A careful analysis of risks and benefits of rapidly reversing anticoagulation must be made prior to the administration of 3F-PCC in this patient population.

Topics: Aged; Anticoagulants; Blood Coagulation Factors; Emergency Service, Hospital; Female; Humans; Intracranial Hemorrhages; Logistic Models; Male; Pulmonary Embolism; Retrospective Studies; Risk Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

The U.S. Food and Drug Administration recently approved a four-factor prothrombin complex concentrate (4-PCC) for warfarin reversal. The literature supporting its use over three-factor prothrombin complex concentrate (3-PCC) is limited.. Our objective was to retrospectively compare the efficacy of 3-PCC to 4-PCC in reversing warfarin in patients who were actively bleeding.. We conducted a single-center, retrospective cohort analysis of adult patients who received 3-PCC or 4-PCC for international normalized ratio (INR) reversal. Our study excluded patients not actively bleeding and not on warfarin. The main outcome was the percentage of patients who achieved warfarin reversal defined as INR ≤ 1.3 at first INR check post factor administration. We recorded baseline data including PCC dose, location of bleed, pre- and posttreatment INR, and time to INR reversal.. We included a total of 53 patients. Intracranial hemorrhage was the most common site of bleeding (26 [74.3%] in 3-PCC vs. 12 [66.7%] in 4-PCC). The mean dose of 3-PCC was 25.5 units/kg, compared to 27.9 units/kg of 4-PCC. The mean baseline INR was 2.3 in the 3-PCC group and 3 in the 4-PCC group (p = 0.03), and the first posttreatment INRs were 1.4 and 1.2, respectively (p < 0.01). Warfarin reversal was achieved in 15 (42.9%) patients who received 3-PCC and 15 (83.3%) patients who received 4-PCC (p < 0.01). Faster time to INR reversal was noted in the 4-PCC group vs. the 3-PCC group (3.7 vs. 5 h, p = 0.48).. A higher percentage of patients achieved warfarin reversal with 4-PCC compared to 3-PCC treatment. A prospective randomized control trial is necessary to confirm our results.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Retrospective Studies; Warfarin

We investigated delayed outcomes of patients with minor head injury, warfarin, and a normal initial head computer tomographic (CT) scan finding.. We conducted a single-center, retrospective study on such patients who were admitted. A second CT was not mandatory. International normalized ratios were classified into subtherapeutic, therapeutic, and supratherapeutic ranges. We traced them 2 weeks after discharge for delayed intracranial hemorrhage (ICH). Primary outcomes were proportions with ICH on second CT, fresh-frozen plasma (FFP) and/or vitamin K administration, and neurosurgical intervention. Secondary outcomes were hospital length of stay and the proportion with ICH 2 weeks after discharge. We explored differences in proportions of ICH during hospital stay among different strata (age ≥65 years, antiplatelet therapy, supratherapeutic international normalized ratio ranges, and FFP administration). Data were analyzed using descriptive statistics. P values less than .05 were considered statistically significant.. We recruited 298 patients. Of admissions (N = 295), 11 (3.7%) had a second CT, with one (0.3%) abnormality. There were 7 (2.4%) and 8 (2.7%) patients who received FFP and vitamin K, respectively. One patient (0.3%) required neurosurgical intervention. The median hospital length of stay was 3 (interquartile range, 2) days. No patients reattended 2 weeks after discharge. There were no statistically significant differences in the proportions of ICH during hospital stay among the 4 strata.. Delayed ICH was rare with no predictive factors. Clinical monitoring before deciding on second CT was safe. The optimal period and mode of observation had yet to be determined.

Topics: Aged; Anticoagulants; Craniocerebral Trauma; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Retrospective Studies; Risk Factors; Time Factors; Tomography, X-Ray Computed; Warfarin

Atrial fibrillation (AF) is the commonest cardiac arrhythmia including in end-stage renal failure patients, but controversy remains whether these patients benefit from anticoagulation. We reviewed the characteristics, management and outcomes of end-stage renal failure patients on dialysis with AF.. All patients started on dialysis at Middlemore Hospital between January 2000 and December 2008 who had AF were studied. Data regarding demographics, co-morbidities, renal disease, AF and embolic, bleeding and/or mortality events were recorded.. There were 141 out of 774(18.2%) dialysis patients with AF followed-up for 4.4+/-2.5 years, and 41.8%(59) were on warfarin. Incidence of all embolic events, ischaemic stroke, all bleeding and intracranial bleed were 4.1, 3.1, 9.6 and 0.82/100 person years respectively. Warfarin anticoagulation was associated with increased risk of intracranial bleed (hazards ratio=11.1, P=0.038), but not total embolic, bleeding events or mortality during follow-up (P=0.317-0.980). All three scores (CHADS2, CHA2DS2-VASc and HAS-BLED) could detect all embolic events (c=0.808-0.838), but not bleeding events (c=0.459-0.498).. Anticoagulation with warfarin didn't significantly reduce embolism or mortality in dialysis patients with AF, but increased the risk of intracranial bleeds. Convention risk scores predict embolic but not bleeding events in these patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Follow-Up Studies; Humans; Intracranial Hemorrhages; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Risk Factors; Warfarin

Warfarin is the most commonly used oral anticoagulant and serious bleeding remains the most feared complication. Excessive warfarin anticoagulation (EWA) can be associated with adverse outcome. We aimed to identify the predictors of adverse clinical outcomes in patients admitted with EWA.. Medical records of patients admitted with EWA from March-2004 through Feb-2015 were reviewed. EWA was defined as international normalized ratio (INR)>3.5 in patients who have been receiving warfarin. Primary outcome was death within hospital and secondary outcome was major composite complications (MCC) defined as intracranial hemorrhage (ICH), a need for transfusing ≥ 4 units packed red blood cell (PRBC), a need for surgical intervention for hemostasis or death within hospital.. 267 patients (153 females and 114 male) were enrolled. 25 patients (9.4%) died during hospitalization. ICH, upper gastrointestinal bleeding and hemoptysis were more common in patients who did not survive (P-value: <0.001, 0.033 and 0.028; respectively). There was no correlation between indication for anticoagulation and death within hospital or development of MCC. In multivariate analysis, O blood group, ICH and the number of transfused PRBC and fresh frozen plasma units were identified as independent predictors of death within hospital. Lower hemoglobin concentrations and higher pulmonary pressures on admission were independent predictors of MCC, which occurred in 47 patients (17.6%).. Hospital mortality correlated with the severity of bleeding (requiring ≥ 4 units PRBC), intracranial hemorrhage and O blood group, while MCC associated with lower hemoglobin and pulmonary hypertension at the time of admission.

Topics: Anticoagulants; Aspirin; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hospital Mortality; Humans; Incidence; Intracranial Hemorrhages; Iran; Male; Platelet Aggregation Inhibitors; Prescription Drug Overuse; Risk Factors; Survival Rate; Thromboembolism; Warfarin

The optimum international normalized ratio (INR) monitoring frequency for hospitalized patients receiving warfarin is unknown.. Assess relationship between daily versus less frequent INR monitoring and overanticoagulation and warfarin-related adverse events.. Retrospective cohort study using Medicare Patient Safety Monitoring System data.. Randomly selected acute care hospitals across the United States.. Patients hospitalized from 2009 to 2013 for pneumonia, acute cardiac disease, or surgery who received warfarin.. None.. (1) Association between frequency of INR monitoring and an INR ≥6.0 or warfarin-related adverse event. (2) Association between the rate of change of the INR and a subsequent INR ≥5.0 and ≥6.0.. Among 8529 patients who received warfarin for ≥3 days, for 1549 (18.2%) the INR was not measured on 2 or more days. These patients had higher propensity-adjusted odds ratios (ORs) of having a warfarin-associated adverse event (OR: 1.48, 95% confidence interval [CI]: 1.02-2.17) for cardiac patients and surgical patients (OR: 1.73, 95% CI: 1.20-2.48), with no significant association for pneumonia patients. Cardiac and pneumonia patients with 1 day or more without an INR measurement had higher propensity-adjusted ORs of having an INR ≥6.0 (OR: 1.61, 95% CI: 1.07-2.41 and OR: 1.92, 95% CI: 1.36-2.71, respectively). A 1-day increase in the INR of ≥0.9 occurred in 621 patients (12.5%) and predicted a subsequent INR of ≥6.0 (positive likelihood ratio of 4.2).. Daily INR measurement and recognition of a rapidly rising INR might decrease the frequency of warfarin-associated adverse events in hospitalized patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Drug Monitoring; Forecasting; Heart Arrest; Hospitalization; Humans; International Normalized Ratio; Intracranial Hemorrhages; Medicare; Middle Aged; Patient Harm; Random Allocation; United States; Warfarin

Whether dabigatran is associated with different risks of cardiovascular, bleeding events, and mortality from warfarin in Asian patients with nonvalvular atrial fibrillation remains unclear.. We used the Taiwan National Health Insurance Research Database to obtain 9940 and 9913 nonvalvular atrial fibrillation patients taking dabigatran and warfarin, respectively, from June 1, 2012, to December 31, 2013, as the dynamic cohort. Inverse probability of treatment weighting using propensity scores was used to balance covariates across 2 study groups. Patients were followed up until the first occurrence of any study outcome or end date of study.. During a median follow-up period of 0.67 years, there were 526 outcomes for dabigatran group. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.62 (0.52-0.73; P<0.0001); myocardial infarction, 0.67 (0.43-1.05; P=0.0803); intracranial hemorrhage, 0.44 (0.32-0.60; P<0.0001); major gastrointestinal bleeding, 0.99 (0.66-1.49; P=0.9658); all hospitalized major bleeding, 0.58 (0.46-0.74; P<0.0001); and all-cause mortality, 0.45 (0.38-0.53; P<0.0001). Dabigatran did not increase the risk of myocardial infarction or major gastrointestinal bleeding in all age groups when compared with warfarin. Total 8772 patients (88%) took a 110-mg dose in dabigatran group. The magnitude of effect for each outcome of 110-mg was comparable with that of 150-mg dose in the subgroup analysis.. In real-world practice, dabigatran was associated with a reduced risk of ischemic stroke, intracranial hemorrhage, all hospitalized major bleeding, and all-cause mortality compared with warfarin in Asian patients with nonvalvular atrial fibrillation. Dabigatran did not increase the risk of major gastrointestinal bleeding or myocardial infarction compared with warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Asian People; Atrial Fibrillation; Brain Ischemia; Cardiovascular Diseases; Case-Control Studies; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Mortality; Myocardial Infarction; Proportional Hazards Models; Risk Factors; Stroke; Taiwan; Warfarin

Oxidative stress has been reported to be a main cause of neuronal cell death in ischemia reperfusion injury (IRI). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important factor involved in anti-oxidative responses. We previously reported that bardoxolone methyl (BARD), an Nrf2 activator, prevented damage induced by IRI. In this study, we investigated the effect of BARD on hemorrhagic transformation in the context of blood brain barrier (BBB) protection.. Mice received pre-treatment with warfarin (4.0 mg/kg, p.o.). IRI was subsequently induced 18 h after the warfarin administration by transient middle cerebral artery occlusion (MCAO) for 6 h. BARD (0.06, 0.2, 0.6 or 2.0 mg/kg) or saline was injected intravenously immediately after reperfusion. The infarct volume, neurological score, intracranial hemorrhage volume, and BBB permeability were evaluated 24 h after MCAO. The survival rate and behavioral functional recovery were evaluated for 7 days following IRI. Furthermore, the effects of BARD on BBB components were investigated by western blotting and immunostaining analysis.. BARD suppressed warfarin-mediated increases in the intracranial hemorrhage volume without affecting the infarct volume. BBB permeability was also suppressed by administration of BARD. Western blotting showed that BARD increased expression of BBB components such as endothelial cells, pericytes, and tight junction proteins. Furthermore, immunostaining showed that BARD induced localization of Nrf2 to endothelial cells and pericytes.. BARD suppressed the exacerbation hemorrhage caused by warfarin pretreatment and ameliorated BBB disruption by protecting endothelial cells, pericytes, and tight junction protein expressions. These results indicate that Nrf2 activators may be an effective therapy against hemorrhagic transformation caused by anticoagulant drugs.

Topics: Animals; Anticoagulants; Antigens, CD; Behavior, Animal; Blood-Brain Barrier; Brain Ischemia; Cadherins; Endothelial Cells; Intracranial Hemorrhages; Male; Mice; Neurons; NF-E2-Related Factor 2; Oleanolic Acid; Pericytes; Reperfusion Injury; Survival Analysis; Tight Junction Proteins; Warfarin

Intracranial hemorrhage (ICH) is the most feared adverse event with oral anticoagulant therapy in patients with atrial fibrillation. The health economic aspects of resuming oral anticoagulant therapy after ICH are unknown. The aim was to estimate hospitalization costs of thromboembolism and hemorrhage subsequent to ICH in 2 patient groups with atrial fibrillation surviving the first 90 days post ICH: (1) patients resuming warfarin therapy within 90 days post ICH and (2) patients discontinuing therapy.. Retrospective data from Danish national registries were linked to identify patients with atrial fibrillation who suffered an ICH between January 1, 1997, and April 1, 2011. Study start was 90 days after incident ICH. Mortality was evaluated using the Kaplan-Meier estimate. Occurrence of hospitalization-requiring thromboembolism and hemorrhage was used to estimate hospitalization costs by linkage of International Classification of Diseases, Tenth Revision, codes to Danish Diagnosis-Related Group tariffs. The effect of resuming warfarin therapy on average 3-year hospitalization costs was estimated by regression analysis adjusted for between-group differences in baseline characteristics.. In the inclusion period, 2162 patients had an ICH; 1098 survived the first 90 days and were included for analysis, and of those, 267 resumed warfarin therapy. Therapy resumption reduced the mean 3-year hospitalization cost of hospitalized patients significantly by US$ 1588 (95% confidence interval, -2925 to -251) and was significantly correlated with fewer hospitalization days per hospitalized patient (-4.6 [95% confidence interval, -7.6 to -1.6]). The marginal effect of therapy resumption on hospitalization costs per patient was US$ -407 (95% confidence interval, -815 to 2).. Resuming warfarin therapy within 90 days after ICH in patients with atrial fibrillation is associated with a decrease in average hospitalization costs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Health Care Costs; Hospitalization; Humans; Intracranial Hemorrhages; Male; Middle Aged; Registries; Retrospective Studies; Warfarin

Time in therapeutic range (TTR), albeit the standard measure of quality of anticoagulation control for warfarin, is underused in everyday clinical practice because of its tedious calculation. In contrast, the percentage of international normalized ratio measurements in range (PINRR) is a convenient alternative. Our objective was to investigate the correlation between PINRR and TTR and whether PINRR has clinical utility for prediction of ischemic stroke and intracranial hemorrhage in a "real-world" atrial fibrillation (AF) cohort.. This is an observational study based on a hospital-based AF registry.. Among 1428 Chinese patients with AF who were taking warfarin (76.2 ± 8.7 years; mean CHA. Among patients with AF who are taking warfarin, the PINRR is a user-friendly alternative to TTR, having a high sensitivity and positive predictive value in predicting TTR. As with TTR, PINRR is associated with clinical adverse events, ie, ischemic stroke and intracranial hemorrhage.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Hong Kong; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Predictive Value of Tests; Registries; Stroke; Warfarin

The risk of further intracranial hemorrhage (ICH) and the benefit of stroke risk reduction with the use of oral anticoagulants for patients who have atrial fibrillation with a history of ICH remain unclear. We aimed to investigate the risks and benefits in patients who have atrial fibrillation with a previous ICH treated with warfarin or antiplatelet drugs in comparison with no antithrombotic therapies.. This study used the National Health Insurance Research Database in Taiwan. Among 307 640 patients who have atrial fibrillation with a CHA2DS2-VASc score ≧2, 12 917 patients with a history of ICH were identified and were assigned to 1 of 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Among patients with previous ICH, the rate of ICH and ischemic stroke in untreated patients was 4.2 and 5.8 per 100 person-years, respectively. The annual ICH and ischemic stroke rates in warfarin users were 5.9% and 3.4%, respectively. Among users of antiplatelet agents, the rates were 5.3% per year and 5.2% per year, respectively. The number needed to treat for preventing 1 ischemic stroke was lower than the number needed to harm for producing 1 ICH with warfarin use for patients with a CHA2DS2-VASc score ≧6 (37 versus 56). The number needed to treat was higher than the number needed to harm for patients with a CHA2DS2-VASc score <6 (63 versus 53).. Warfarin use may be beneficial for patients who have atrial fibrillation with a previous ICH having a CHA2DS2-VASc score ≧6. Whether the use of non-vitamin K antagonist oral anticoagulants could lower the threshold for treatment deserves further study.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Follow-Up Studies; Humans; Intracranial Hemorrhages; Male; Middle Aged; Population Surveillance; Stroke; Taiwan; Warfarin

The efficacy and safety of warfarin therapy for stroke prevention in atrial fibrillation (AF) depends on the time in therapeutic range (TTR). We aimed to assess the predictive ability of SAMe-TT2R2 score in Chinese AF patients on warfarin, whose TTR is notoriously poor.. This is a single-centre retrospective study. Patients with non-valvular AF on warfarin diagnosed between 1997 and 2011 were stratified according to SAMe-TT2R2 score, and TTR was calculated using Rosendaal method. The predictive power of SAMe-TT2R2 scores for good TTR i.e. >70% was assessed. We included 1,428 Chinese patients (mean age 76.2±8.7 years, 47.5% male) with non-valvular AF on warfarin. The mean and median TTR were 38.2±24.4% and 38.8% (interquartile range: 17.9% and 56.2%) respectively. TTR decreased progressively with increasing SAMe-TT2R2 score (p = 0.016). When the cut-off value of SAMe-TT2R2 score was set to 2, the sensitivity and specificity to predict TTR<70% were 85.7% and 17.8%, respectively. The corresponding positive and negative predictive values were 10.1% and 92.0%. After a mean follow-up of 4.7±3.6 years, 338 patients developed an ischemic stroke (4.96%/year). Patients with TTR≥70% had a lower annual risk of ischemic stroke of 3.67%/year compared with than those with TTR<70% (5.13%/year)(p = 0.08). Patients with SAMe-TT2R2 score ≤2 had the lowest risk of annual risk of ischemic stroke (3.49%/year) compared with those with SAMe-TT2R2 score = 3 (4.56%/year), and those with SAMe-TT2R2 score ≥4 (6.41%/year) (p<0.001). There was also a non-significant trend towards more intracranial hemorrhage with increasing SAMe-TT2R2 score.. The SAMe-TT2R2 score correlates well with TTR in Chinese AF patients, with a score >2 having high sensitivity and negative predictive values for poor TTR. Ischemic stroke risk increased progressively with increasing SAMe-TT2R2 score, consistent with poorer TTRs at high SAMe-TT2R2 scores.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Incidence; Intracranial Hemorrhages; Male; Retrospective Studies; Risk Factors; Stroke; Warfarin

Concomitant use of vitamin K antagonist (VKA) and aspirin (ASA) is becoming increasingly prevalent among atrial fibrillation (AF) patients. We quantified the net clinical benefit of adding ASA to a VKA using nationwide prospective AF registry data.. We studied 6074 patients (VKA monotherapy: 83% and VKA+ASA: 17%) between January 2009 and July 2009, and followed them for a mean follow-up period of 2years. The risk of strokes and bleeding was calculated by the CHA2DS2-VASc and HAS-BLED scores. The net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by VKAs minus intracranial hemorrhages attributable to the VKA+ASA, multiplied by an impact weight of 1.5.. Patients on a VKA+ASA were older with more medical comorbidities than those on VKA alone. Using VKA monotherapy as a reference, higher major bleeding rates and all-cause death were evident in those on VKA+ASA. The net clinical benefit of VKA+ASA for the overall cohort was -0.1%/year (95% confidence interval, -0.74% to 0.46%). There was a trend toward a negative net clinical benefit from VKA+ASA in patients with a CHA2DS2-VASc≥2 and HAS-BLED≤2 (-1.17%/year). The VKA+ASA yielded a positive net clinical benefit in patients with a CHA2DS2-VASc≥2 and HAS-BLED≥3 (1.16%/year). The result patterns were relatively constant using impact weight of 1.0 and 2.0.. Our estimates of the net clinical benefit can provide a useful anchoring point for adding ASA to VKA in patients with AF.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Prospective Studies; Risk Assessment; Stroke; Treatment Outcome; Warfarin

Topics: Aged; Anticoagulants; Blood Coagulation Factors; Coagulants; Fatal Outcome; Humans; Hypotension; Intracranial Hemorrhages; Male; Warfarin

To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines.. We used the "National Health Insurance Research Database" in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively.. The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94).. In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF.

Topics: Administration, Oral; Age Distribution; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; Insurance Claim Review; Intracranial Hemorrhages; Male; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Risk Assessment; Sex Distribution; Stroke; Taiwan; Vascular Diseases; Warfarin

The use of vitamin K antagonists is an independent risk factor for the development of intracerebral hemorrhage (ICH). Four-factor prothrombin complex concentrate (4F-PCC) is recommended for urgent reversal of anticoagulation in this setting. The safety and efficacy of 4F-PCC in ICH with subtherapeutic levels of anticoagulation is yet to be determined.. This was a retrospective, observational study of 4F-PCC administration data from September 2013 to July 2015. Patients with spontaneous or traumatic ICH with initial INR 1.4-1.9 were compared to those with INR 2-3.9. A Fisher's exact test was used to compare the difference between the two groups in the effectiveness of 4F-PCC in reversing the INR to ≤1.3 and in the occurrence of thrombotic events within 7 days of administration.. A total of 131 patients with a presenting INR between 1.4 and 3.9 received 4F-PCC during the study period. Twenty-three of 29 patients (79 %) in the INR <2 group achieved an INR reduction to ≤1.3 after 4F-PCC administration compared to 47 of 92 patients (51 %) in the INR 2-4 group, p = 0.03. There was no difference in thrombotic complications within 7 days after administration (6.7 % in INR 1.4-1.9 group, 10 % in INR 2-3.9 group, p = 0.73).. The use of 4F-PCC in patients with INR between 1.4 and 1.9 results in an effective reduction in INR with similar thrombotic risks compared to patients presenting with an INR of 2-3.9.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Warfarin

Atrial fibrillation (AF) is a common cardiac arrhythmia. Dabigatran etixalate (DE) is one of the new oral anticoagulant drugs being used in nonvalvular AF (NVAF). There is no adequate real world data in different populations about DE. The aim of this registry was to evaluate the efficacy and safety of DE Consecutive NVAF patients treated with warfarin or both DE doses were enrolled during 18 months study period. The patients were re-evaluated at regular 6-month intervals during the follow-up period. During the follow-up period outcomes were documented according to RELY methodology A total of 555 patients were analyzed. There was no significant difference in ischemic stroke rates (p = 0.73), death rates (p = 0.15) and MI rates (p = 0.56) between groups. The rate of major bleeding was significantly higher in warfarin and dabigatran 150 mg group than dabigatran 110 mg (p < 0.001). Intracranial bleeding rate and relative risk were significantly lower in dabigatran 110 mg group than warfarin group (p = 0.004). Dyspepsia was significantly higher in both DE doses than warfarin (p = 0.004) Both DE doses are as effective as warfarin in reducing stroke rates in NVAF patients, without increasing MI rates. Intracranial bleeding rates are significantly lower in warfarin than both doses of DE and gastrointestinal bleeding risk increases with increased DE doses.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Dyspepsia; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Registries; Stroke; Warfarin

The optimal management of major bleeding associated with vitamin K antagonists remains unclear.. The aim of the study was to assess the determinants of outcome of vitamin K antagonists-associated major bleeding and the outcome of bleeding in relation with the therapeutic management.. Patients hospitalized for major bleeding while on vitamin K antagonists were included in a prospective, cohort study. Major bleeding was defined according to the criteria of the International Society of Thrombosis Haemostasis. The primary study outcome was death at 30days from major bleeding.. 544 patients were included in this study, of which 282 with intracranial hemorrhage. Prothrombin complex concentrates were used in 51% and in 23% of patients with intracranial hemorrhage or non-intracranial major bleeding, respectively (p<0.001); fresh frozen plasma was used in 7% and in 17% of patients with intracranial hemorrhage or non-intracranial major bleeding (p<0.001). Death at 30days occurred in 100 patients (18%), 72 patients with intracranial hemorrhage and 28 patients with non-intracranial major bleeding. Age over 85years, low Glasgow Coma Scale score and shock were independent predictors of death at 30days. Invasive procedures were associated with decreased risk of death.. Among the patients hospitalized for major bleeding while on vitamin K antagonists, the risk for death is substantial. The risk for death is associated with the clinical severity of major bleeding as assessed by the GCS score and by the presence of shock more than with the initial localization of major bleeding (ICH vs other sites).

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Disease Management; Female; Fibrinolytic Agents; Glasgow Coma Scale; Humans; International Normalized Ratio; Intracranial Hemorrhages; Italy; Length of Stay; Male; Middle Aged; Plasma; Prognosis; Proportional Hazards Models; Prospective Studies; Vitamin K; Warfarin

Randomized controlled trials (RCTs) have shown that dabigatran, rivaroxaban and warfarin cause similar bleeding rates.. We performed a retrospective population-based cohort study to determine the incidence of bleeding in patients with atrial fibrillation (AF) beginning dabigatran, rivaroxaban or warfarin. Consecutive patients initiating anticoagulation for AF during a 3year period were identified using a computerized database. Patients who bled and required hospitalization underwent chart review. Bleeding incidences were calculated per 100 patient-years of treatment.. 18,249 patients were included: 9564 (52.4%) received warfarin, 5976 (32.7%) dabigatran, and 2709 (14.8%) rivaroxaban. Bleeding incidences were 3.9 (95% CI, 3.6-4.4) in warfarin-treated patients, 4.2 (95% CI, 3.7-4.7) in dabigatran patients, and 4.1 (95% CI, 3.0-5.3) in rivaroxaban patients. Intracranial hemorrhage (ICH) rates were 0.71 (95% CI, 0.56-0.90) for warfarin, 0.4 (95% CI, 0.18-0.87) for dabigatran, and 0.27 (95%CI, 0.10-0.80) for rivaroxaban. GI hemorrhage rates were 1.88 (95%CI, 1.62-2.20) for warfarin, 2.98 (95% CI, 2.4-3.5) for dabigatran and 2.39 (95%CI, 1.6-3.5) for rivaroxaban.. We demonstrate similar bleeding rates with both dabigatran 150mg and 110mg and rivaroxaban compared to warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Israel; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

The use of antithrombotic medication (ATM) frequently is reported in patients with intracranial hemorrhage (ICH) and is associated with increased mortality. Unfortunately, ATMs sometimes are prescribed and/or used inappropriately. We sought to determine the rate of ATM misprescription/misuse among patients with ICH in a single-center retrospective study.. All patients admitted with ATM-related ICH in 1998-2014 were included. Charts were reviewed and demographic, clinical, and radiologic variables were recorded. The type of ATM, dose, and duration of treatment were analyzed critically. The adequacy of ATM prescription/use was assessed in light of the recommendations and guidelines of the American Heart Association, American Stroke Association, and French National Authority for Health, in effect at the time of admission.. A total of 106 patients with mean age 68 years were identified. Aspirin (53.8%) was the most commonly used drug, followed by oral anticoagulants (31.1%) and clopidogrel (22.6%). In only 80 patients (75.5%), the use of ATM was in line with contemporary guidelines. In the remaining 26 (24.5%), the use of ATMs was inappropriate, including bad drug combination, wrong dose, poor indication, wrong drug class, and/or incorrect treatment duration.. In this Lebanese cohort of patients with ICH, the 24.5% rate of ATM misprescription and/or misuse is highly alarming and the origin of this problem is likely multifactorial. Immediate measures should be undertaken, and efforts should be focused on regaining tight control of ATM prescription and fulfillment, ensuring good patient education, and offering more vigilant oversight on physician licensure.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Clopidogrel; Coronary Artery Disease; Enoxaparin; Female; Fibrinolytic Agents; Humans; Inappropriate Prescribing; Intracranial Hemorrhages; Lebanon; Male; Middle Aged; Platelet Aggregation Inhibitors; Prescription Drug Misuse; Retrospective Studies; Risk Factors; Stroke; Ticlopidine; Warfarin; Young Adult

Previous trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria.. This was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed.. Ninety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K.. 4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Cardiac Surgical Procedures; Dabigatran; Emergencies; Female; Gastrointestinal Hemorrhage; Heart Transplantation; Hemorrhage; Hemostatics; Heparin; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Laparotomy; Male; Middle Aged; Preoperative Care; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Surgical Procedures, Operative; Thrombocytopenia; Thromboembolism; Vitamin K; Warfarin

The effect of oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF) with a history of intracranial hemorrhage (ICH) is poorly defined.. The purpose of this study was to evaluate the efficacy and safety of OAT in patients with AF with an ICH history.. We retrospectively compared the composite end point, including thromboembolic and major bleeding events, between patients with AF with a history of ICH who were (OAT group, n = 254) and those who were not (no-OAT group, n = 174) taking OAT.. During a mean follow-up of 39.5 ± 31.9 months, 5.5 and 3.1 major bleeding events/100 patient-years were observed in the OAT and no-OAT groups, respectively (P = .024). Recurrent ICH was observed only in patient with OAT. Thromboembolic events occurred in 2.4 and 8.3 events/100 patient-years in OAT and no-OAT groups, respectively (P < .001). There was no significant differences in composite end points between OAT and no-OAT groups (11.5 events/100 patient-years vs 7.9 events/100 patient-years; P = .154). Patients with OAT who achieved a time-in-therapeutic range of ≥60% of the international normalized ratio of 2.0-3.0 demonstrated a better cumulative survival free of the composite end point (P < .001) than did patients without OAT. Early (<2 weeks) OAT after an index ICH did not improve composite end points because of the increased incidence of major bleeding events. However, OAT at 2 weeks after an index ICH was associated with decreased clinical events including thromboembolic events and composite end point.. In patients with AF who require anticoagulation and have a history of ICH, maintaining optimal OAT with time-in-therapeutic range ≥ 60% and the initiation of OAT at least 2 weeks after an index ICH were associated with improved clinical outcomes.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Assessment; Stroke; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Warfarin

It is unclear whether the non-vitamin K antagonist oral anticoagulant agents rivaroxaban and dabigatran are superior to warfarin for efficacy and safety outcomes in Asians with nonvalvular atrial fibrillation (NVAF).. The aim of this study was to compare the risk for thromboembolic events, bleeding, and mortality associated with rivaroxaban and dabigatran versus warfarin in Asians with NVAF.. A nationwide retrospective cohort study was conducted of consecutive patients with NVAF taking rivaroxaban (n = 3,916), dabigatran (n = 5,921), or warfarin (n = 5,251) using data collected from the Taiwan National Health Insurance Research Database between February 1, 2013 and December 31, 2013. The propensity score weighting method was used to balance covariates across study groups. Patients were followed until the first occurrence of any study outcome or the study end date (December 31, 2013).. A total of 3,425 (87%) and 5,301 (90%) patients were taking low-dose rivaroxaban (10 to 15 mg once daily) and dabigatran (110 mg twice daily), respectively. Compared with warfarin, both rivaroxaban and dabigatran significantly decreased the risk for ischemic stroke or systemic embolism (p = 0.0004 and p = 0.0006, respectively), intracranial hemorrhage (p = 0.0007 and p = 0.0005, respectively), and all-cause mortality (p < 0.0001 and p < 0.0001, respectively) during the short follow-up period. In comparing the 2 non-vitamin K antagonist oral anticoagulant agents with each other, no differences were found regarding risk for ischemic stroke or systemic embolism, intracranial hemorrhage, myocardial infarction, or mortality. Rivaroxaban carried a significantly higher risk for hospitalization for gastrointestinal bleeding than dabigatran (p = 0.0416), but on-treatment analysis showed that the risk for hospitalized gastrointestinal bleeding was similar between the 2 drugs (p = 0.5783).. In real-world practice among Asians with NVAF, both rivaroxaban and dabigatran were associated with reduced risk for ischemic stroke or systemic embolism, intracranial hemorrhage, and all-cause mortality without significantly increased risk for acute myocardial infarction or hospitalization for gastrointestinal bleeding compared with warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Asian People; Atrial Fibrillation; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Assessment; Rivaroxaban; Stroke; Thromboembolism; Warfarin

A 34-year-old man presented with an acute onset of upbeat nystagmus, slurred speech, and limb and truncal ataxias. The patient had a history of limb ataxia and gait disturbance previously treated as brainstem encephalitis with corticosteroids 3 years previously. Brain magnetic resonance imaging showed pontine developmental venous anomaly (DVA) and hemorrhagic infarction within the drainage territory of the DVA. Three months later, the patient exhibited recurrent limb ataxia, double vision, and numbness of the left side of the body. The brain magnetic resonance imaging revealed recurrent hemorrhagic venous infarction within the same territory of the pontine DVA. Laboratory tests disclosed a hypercoagulable state owing to a decrease of protein S activity despite the normal antigen level. Genetic testing indicated that the patient was a homozygous carrier of protein S Tokushima. The patient's severe disability remained unchanged in spite of treatment with anticoagulation therapy using warfarin. We propose that further research on hereditary coagulopathy be carried out in patients with recurrent episodes of DVA-related infarction.

Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Brain Infarction; Central Nervous System Vascular Malformations; Cerebral Angiography; Cerebral Veins; DNA Mutational Analysis; Homozygote; Humans; Intracranial Hemorrhages; Intracranial Thrombosis; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Mutation; Pons; Protein S; Protein S Deficiency; Recurrence; Treatment Outcome; Venous Thrombosis; Warfarin

Warfarin-related intracranial haemorrhage (WRICH) is a life-threatening complication of warfarin use. Rapid and complete reversal of the coagulopathy is required. Reversal protocols which include prothrombin complex concentrates (PCC) are now recommended. We report on a quality improvement project to implement and refine such a protocol.. Retrospective and then prospective audits of all WRICH patients presenting to a single centre. The protocol development and subsequent refinements are described. Outcomes included times to scanning, treatment and overall door-needle times, as well as use of PCC.. Across the three cohorts, use of PCC increased over time from 15% to 100% of eligible patients (p<0.001). There were significant improvements in median time to scanning (1.9 to 1.5 to 1.3 hours, p=0.03) and median door-needle times (4.5 to 2.9 to 1.9 hours, p=0.018). Key steps in the change process included (1) identifying need for change, (2) utilising senior clinical opinion leaders, (3) using "Plan-do-study-act" cycles, (4) involvement of all relevant stakeholders, (5) having a broad implementation and education plan, (6) a "change friendly" environment and (7) collaborating across departments.. The introduction (and revisions) of an anticoagulation reversal strategy for WRICH has led to increased PCC use and reduced times to both diagnosis and treatment. Further work is required to improve door-needle times and monitoring.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Humans; Intracranial Hemorrhages; Retrospective Studies; Time Factors; Treatment Outcome; Warfarin

Aortic false aneurysm is life-threatening with high morbidity and mortality rates. Surgical treatment varies according to the pathologic process, infection status, and site of origin of the aneurysm. We presented a case of false aneurysm of the ascending aorta, developing after type A acute aortic dissection repair. The operation was performed with the use of deep hypothermia and circulatory arrest to avoid massive uncontrollable hemorrhage.

Topics: Acute Disease; Aneurysm, False; Anticoagulants; Aortic Aneurysm; Aortic Dissection; Aortography; Blood Vessel Prosthesis Implantation; Circulatory Arrest, Deep Hypothermia Induced; Debridement; Drug Overdose; Fatal Outcome; Humans; Intracranial Hemorrhages; Male; Middle Aged; Reoperation; Stroke; Suture Techniques; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Edoxaban, an oral direct factor Xa inhibitor, has been found non-inferior to warfarin for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), with a lower rate of intracranial bleeding. The aim of our investigation was to assess the cost-effectiveness of edoxaban versus warfarin from the perspective of the Italian health-care system. A Markov decision model was used to evaluate lifetime cost and quality-adjusted life expectancy of NVAF patients treated with warfarin or edoxaban. Transition probabilities were obtained from the ENGAGE AF-TIMI 48 trial, cost estimates were based on Italian prices and tariffs, utilities were obtained from the literature. One-way and second-order sensitivity analyses were performed. In the base case, lifetime costs were €18,658 for edoxaban and €14,060 for warfarin. Discounted quality-adjusted survival was 9.022 years for edoxaban and 8.425 years for warfarin, leading to an incremental cost-utility ratio of €7,713 per quality-adjusted life year (QALY) gained. Results were sensitive to time horizon, time in therapeutic range of warfarin and to the relative impact of warfarin versus edoxaban therapy onto quality of life. Probabilistic sensitivity analysis showed edoxaban to be cost-effective versus warfarin in 92.3 % of the simulations at a willingness-to-pay threshold of €25,000 per QALY. In conclusion, edoxaban proved to be a cost-effective alternative to warfarin in patients with moderate-to-high-risk NVAF.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Humans; Intracranial Hemorrhages; Italy; Markov Chains; Pyridines; Quality-Adjusted Life Years; Stroke; Thiazoles; Warfarin

To maximize protection against stroke with minimal bleeding, warfarin therapy in nonvalvular atrial fibrillation (NVAF) requires tight control within a narrow therapeutic range, which might depend on racial variations.. The J-RHYTHM Registry followed 6404 NVAF patients treated with warfarin for 2 years. Using international normalized ratios (INRs) at or closest to the embolic and intracranial hemorrhagic (ICH) events, we determined odds ratios for ischemic stroke/systemic embolism (SE) and ICH according to any given INR with a reference INR range including 2.0.. Ischemic stroke and SE occurred in 97 of the patients and ICH occurred in 49. The estimated INR-risk relationships showed characteristics of Japanese NVAF patients. Compared to INR-risk relationships reported for Westerners, those observed in Japanese patients were virtually identical for ischemic stroke/SE and shifted leftward by approximately 0.5 INR for ICH.. This is the largest Japanese study providing fundamental data necessary to establish optimal anticoagulation intensities. Japanese NVAF patients may require narrower therapeutic ranges than Westerners.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Japan; Male; Middle Aged; Odds Ratio; Registries; Risk; Stroke; Warfarin

The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established.. We formed new-user cohorts of propensity score-matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67-0.96); intracranial hemorrhage, 0.34 (0.26-0.46); major gastrointestinal bleeding, 1.28 (1.14-1.44); acute myocardial infarction, 0.92 (0.78-1.08); and death, 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis.. In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Comorbidity; Dabigatran; Dose-Response Relationship, Drug; Follow-Up Studies; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Kidney Diseases; Medicare; Proportional Hazards Models; Retrospective Studies; Risk; Socioeconomic Factors; Stroke; Treatment Outcome; United States; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Stroke; Warfarin

Little is known about the impact of quality of anticoagulation control, as reflected by time in therapeutic range (TTR), on the effectiveness and safety of warfarin therapy in Chinese patients with atrial fibrillation. We investigated the risks of ischemic stroke and intracranial hemorrhage (ICH) in relation to warfarin at various TTRs in a real-world cohort of Chinese patients with atrial fibrillation receiving warfarin and compared with those on dabigatran, aspirin, and no therapy.. This is an observational study.. Of 8754 Chinese patients with atrial fibrillation and CHA2DS2-VASc ≥1 (79.5±9.2 years; CHA2DS2-VASc, 4.1±1.5; and Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly (>65 years), Drugs/Alcohol Concomitantly [HAS-BLED], 2.2±0.9), 16.3% received warfarin, 41.1% aspirin, 4.5% dabigatran, and 38.1% received no therapy. The incidence of ischemic stroke was highest in patients with no therapy (10.38%/y), followed by patients on aspirin (7.95%/y). The incidence of stroke decreased progressively with increasing TTR quartiles (<17.9%, 17.9%-38.8%, 38.8%-56.2%, and >56.2%) from 7.34%/y (first quartile) to 3.10%/y (fourth quartile). Patients on dabigatran had the lowest incidence of stroke among all groups (2.24%/y). The incidence of ICH was lowest in patients on dabigatran (0.32%/y) compared with those on warfarin (0.90%/y), aspirin (0.80%/y), and no therapy (0.53%/y). ICH incidence decreased with increasing TTR from 1.37%/y (first quartile) to 0.74%/y (fourth quartile).. In Chinese patients with atrial fibrillation, the benefits of warfarin therapy for stroke prevention and ICH risk are closely dependent on the quality of anticoagulation, as reflected by TTR. Even at the top TTR quartile, warfarin was associated with a higher stroke and ICH risk than dabigatran.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; beta-Alanine; China; Cohort Studies; Dabigatran; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Stroke; Time Factors; Warfarin

The risk of ischemic stroke/thromboembolic events after an intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) who are on warfarin treatment is poorly characterized. The aim of this study was to assess the association between the risk of ischemic stroke/thromboembolic events and ICH.. Linkage of three Danish nationwide administrative registries in the period between 1999 and 2012 identified patients with AF on warfarin treatment. Event-rate ratios of stroke/thromboembolic events, major bleeding, and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched OR was calculated for ICH occurrences within 0 to 3 months relative to the 3 to 6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated.. We studied 58,815 patients with AF (median age, 72.6 years; 60% men). When compared with the non-ICH group, the ICH group was at increased risk for stroke/systemic embolism/transient ischemic attack (TIA) (rate ratio, 3.67; 95% CI, 3.12-4.31) and mortality (rate ratio, 5.55; 95% CI, 5.20-5.92), but not for major bleeding (rate ratio, 1.06; 95% CI, 0.81-1.39). The matched OR of ICH occurrences prior to a stroke/systemic embolism/TIA was 4.33 (95% CI, 2.44-8.15). The rate ratio of claimed warfarin prescriptions post- and pre-ICH event was 0.28 (95% CI, 0.24-0.33).. In this large-scale study of patients with AF treated with warfarin, first-time ICH was associated with an increased rate of ischemic stroke/systemic embolism/TIA and mortality compared with the non-ICH group. There was a decrease in the warfarin-prescription purchase rate in the post-ICH period compared with pre-ICH, which may partly explain the excess risk.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Denmark; Embolism; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Prevalence; Registries; Retrospective Studies; Risk Factors; Stroke; Survival Rate; Warfarin

There is little evidence to guide physicians on management of patients who sustain head injuries while on warfarin.. Our objective was to determine the rate of intracranial bleeding in anticoagulated patients with minor and minimal head injuries and the association with clinical features and international normalized ratio (INR).. We conducted a historical cohort study of adult patients, taking warfarin, at two tertiary care emergency departments over 2 years with minor (Glasgow Coma Score 13-15, with loss of consciousness, amnesia, or confusion) or minimal (Glasgow Coma Score 15 without loss of consciousness, amnesia, or confusion) head injuries. Patients with penetrating injuries, INR < 1.5, or a new focal neurological deficit were excluded. Our outcome, intracranial bleeding, was determined by the radiologist's final computed tomography (CT) report for imaging performed within 2 weeks.. There were 176 patients enrolled, of which 157 (89.2%) had CT and 28 (15.9%) had intracranial bleeding. Comparing patients with and without intracranial bleeding found no significant differences in INR, and loss of consciousness was associated with higher rate of intracranial bleeding. The rate of intracranial bleeding in the minor and minimal head injury groups was 21.9% and 4.8%, respectively.. The rate of intracranial bleeding in patients on warfarin is considerable. Loss of consciousness is associated with high rates of intracranial bleeding. This study supports a low threshold for ordering CT scans for anticoagulated patients with head injuries.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Craniocerebral Trauma; Emergency Service, Hospital; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Factors; Tomography, X-Ray Computed; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Randomized Controlled Trials as Topic; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Stroke; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Stroke; Warfarin

To define the relationship between preinjury warfarin use and mortality in a large European sample of trauma patients.. A multicentred study was conducted using data collated from European (predominately English and Welsh) trauma receiving hospitals. Patient data from the Trauma Audit and Research Network database from 2009 to 2013 were analysed. Univariate and multivariate logistic regression was used to estimate OR for mortality associated with preinjury warfarin use in the whole adult trauma cohort and a matched sample of patients comparable in terms of age, gender, GCS, pre-existing medical conditions and injury severity.. A total of 136 617 adult trauma patients (2009-2013) were included, with 499 patients reported to be using warfarin therapy at the time of trauma. Preinjury warfarin use was associated with a significantly higher mortality rate at 30 days postinjury compared with the non-users. Following adjustment of age, injury severity and GCS, preinjury warfarin use was associated with increased mortality in trauma patients (adjusted OR 2.14; 95% CI 1.66 to 2.76; p<0.001). In the matched subset, 22% of warfarinised trauma patients died compared with 16.3% of non-warfarinised trauma patients with comparable age, injury severity and GCS (adjusted OR 1.94; 95% CI 1.25 to 3.01; p=0.003).. Preinjury warfarin use has been demonstrated to be an independent predictor of mortality in trauma patients. Clinicians managing major trauma patients on warfarin need to be aware of the vulnerability of this group.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Europe; Female; Glasgow Coma Scale; Hospital Mortality; Humans; Injury Severity Score; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Odds Ratio; Retrospective Studies; Sex Factors; Trauma Centers; Warfarin; Wounds and Injuries; Young Adult

We assess the in-vivo relationship between international normalized ratio (INR) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate (PCC) for warfarin reversal. This was a prospective pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin. Thromboelastography (TEG), thrombin generation parameters and INR were assessed at baseline, 30  min, 2 and 24  h after PCC. Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time. Eight patients mean [standard deviation (SD)] age 72 (16) were included and received mean (SD) dose of PCC 24 (5) units/kg. Four patients died during the study, all with INR values more than 1.5 thirty minutes after PCC. Mean (SD) INR was 3.0 (1.3) and decreased significantly to 1.8 (0.48) thirty minutes after PCC (P < 0.01). Baseline endogenous thrombin potential and thrombin peak were 890  nmol/min and 123  nmol and increased significantly to 1943  nmol/min (P < 0.01) and 301  nmol (P < 0.01) 30  min after PCC administration. Reaction (R)-time decreased significantly (P = 0.02), and maximum amplitude and overall coagulation index (CI) significantly increased during treatment (P < 0.01, respectively). Thrombin generation and TEG values corrected after PCC administration; however, INR did not fully correct. Patients that died tended to be older with prolonged INR values across the study period. INR and TEG values correlated well with thrombin generation before administration of PCC, but this relationship was lost afterward.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pilot Projects; Prospective Studies; Thrombelastography; Warfarin

Topics: Anticoagulants; Cerebral Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Warfarin

Previous studies of traumatic brain injury (TBI) outcomes in elderly patients on oral antithrombotic (OAT) therapies have yielded conflicting results. Our objective was to examine the effect of premorbid OAT medications on outcomes among elderly TBI patients with intracranial hemorrhage.. We performed a retrospective analysis of elderly TBI patients (≥65 years) with closed head injury and evidence of brain hemorrhage on computed tomography scan from 2006 to 2010. Patient demographics, injury severity, clinical course, hospital and intensive care unit length of stay, and disposition were collected. Comparison of patients stratified by premorbid OAT use was performed using nonparametric Kruskal-Wallis and Fisher's exact tests. Multivariable logistic regression was used to compare groups and identify predictors of primary outcomes, including mortality, neurosurgical intervention, hemorrhage progression, complications, and infection.. A total of 1,552 patients were identified: 543 on aspirin only, 97 on clopidogrel only, 218 on warfarin only, 193 on clopidogrel and aspirin, and 501 on no antithrombotic agent. Blood products were administered to reverse coagulopathy in 77.3% of patients on antithrombotic medications. After adjusting for covariates, including medication reversal, OAT use was associated with increased mortality (p = 0.04). Warfarin use was identified as a key predictor (odds ratio, 2.27; p = 0.05), in contrast to the preinjury use of antiplatelet medications, which was not associated with increased risk of in-hospital death. Rates of neurosurgical intervention differed between groups, with patients on warfarin undergoing intervention more frequently. Survivor subset analysis demonstrated that hemorrhage progression was not associated with preinjury antithrombotic therapy, nor were rates of complication or infection, hospital and intensive care unit lengths of stay, or ventilator days.. Preinjury use of warfarin, but not antiplatelet medications, influences survival and need for neurosurgical intervention in elderly TBI patients with intracranial hemorrhage; hemorrhage progression and morbidity are not affected. The importance of antithrombotic therapy may lie in its impact on initial injury severity.. Epidemiologic study, level III.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Brain Injuries; Clopidogrel; Female; Humans; Intracranial Hemorrhages; Length of Stay; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Survival Rate; Ticlopidine; Tomography, X-Ray Computed; Trauma Severity Indices; Warfarin

Topics: Anticoagulants; Cerebral Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Warfarin

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Pressure; Comorbidity; Diet; Dose-Response Relationship, Drug; Endoscopy, Digestive System; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Medical History Taking; Polypharmacy; Referral and Consultation; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Intracranial Hemorrhages; Male; Warfarin

Dabigatran and warfarin are oral anticoagulant drugs widely used for the prevention of stroke in patients with atrial fibrillation. The objective of this study was to evaluate the interaction between aging and dabigatran- and warfarin-induced gastrointestinal (GI) and nervous system hemorrhage using data available in the FDA Adverse Event Reporting System (FAERS) database. We analyzed reports of hemorrhagic events in the GI and nervous system recorded in the FAERS database between 2004 and 2014 using an adjusted reporting odds ratio (ROR). We demonstrated that dabigatran-associated GI hemorrhage was significantly increased in patients over the age of 80 years. The RORs of dabigatran increased with increasing age, although aging had little effect on warfarin-associated GI hemorrhage. The ROR for anticoagulant-associated nervous system hemorrhage was not significantly affected by aging, as compared to GI hemorrhage. Our results indicate that the excretion of dabigatran may be affected by aging, as compared to warfarin, likely due to renal function decline. Our results emphasize the need for physicians to closely monitor GI bleeding in aging patients, because it is closely related to renal function deterioration.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Aged, 80 and over; Aging; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Kidney; Male; Middle Aged; Odds Ratio; United States; United States Food and Drug Administration; Warfarin

This study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention.. We used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives.. Overall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention.. Our results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient's condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Decision Support Techniques; Embolism; Evidence-Based Medicine; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Rivaroxaban; Stroke; Warfarin

Since 2010, several novel oral anticoagulants (NOACs) have been approved by the United States Food and Drug Administration for the use in the prevention of cerebrovascular accidents (CVAs) in nonvalvular atrial fibrillation.. Our aim was to describe the trends and characteristics of NOAC-related emergency department (ED) visits.. Retrospective review of data from an ED tracking system of all visits that had a medication reconciliation with an NOAC or warfarin to a tertiary care ED between October 2010 and August 2014. Basic demographics, admission rate, admission diagnoses, and trends were analyzed.. The rate of warfarin visits was stable at 50-60 patients per month (PPM) per 1000 ED visits, however, the rate of dabigatran visits rose to 3-5 PPM/1000 until 2012 and has stayed stable, while rivaroxaban and apixaban have been gradually increasing to 2-4 and 1-2 PPM/1000, respectively. The admission rate for warfarin was 63.7% and for NOACs was 58.1%, compared to baseline admission rate of 35.5%. The hemorrhagic diagnosis rate was similar for warfarin and the NOACs (8.8% and 8.0%, respectively). There were three significantly different admission diagnoses: there were more admission for atrial fibrillation (5.4% vs. 1.9%) and CVA/transient ischemic attack (5.3% vs. 3.0%) in the NOAC group, while there were more admissions for intracranial hemorrhage (2.7% vs. 0.8%) in the warfarin group.. There has been a steady increase of ED patients who are taking an NOAC. There is a nearly double admission rate for an anticoagulated patient regardless of reason for ED visit. There appears to be no difference between rates of bleeding between warfarin and NOACs, although patients taking NOACs are admitted less often for intracranial hemorrhage.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Emergency Service, Hospital; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Patient Admission; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

Topics: Aged; Antidotes; Antithrombins; Atrial Fibrillation; Blood Coagulation Factors; Blood Transfusion; Clinical Protocols; Clinical Trials, Phase III as Topic; Disease Management; Drug Design; Factor Xa Inhibitors; Hemorrhage; Hemostatic Techniques; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Meta-Analysis as Topic; Neoplasms; Perioperative Care; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Assessment; Thrombophilia; Vulnerable Populations; Warfarin

Current literature estimates the risk of delayed intracranial hemorrhage as between 0.6 and 6% after mild head injury for patients on warfarin. Due to resource allocation issues, the need to actually diagnose delayed intracranial haemorrhage has been questioned, especially if it does not require surgery. The purpose of our case report is to consider the functional implications during the six months following a mild traumatic brain injury complicated by delayed intracranial hemorrhage in a patient undergoing warfarin therapy. To the best of our knowledge, the rehabilitative and functional considerations of delayed intracranial haemorrhage in head injury have not been previously described in the literature.. A previously independent 74-year-old Lebanese man living in Australia sustained mild traumatic brain injury following an unwitnessed fall from the height of two meters while on warfarin therapy, with an international normalized ratio of 4.2. He was found to have amnesia of the event and extensive facial bruising. His Glasgow Coma Scale score was 14 to 15 throughout observation. Following a non-diagnostic initial computerised tomography scan, a repeat scan at 24 hours from the injury identified large intracerebral, subdural and subarachnoid hemorrhages. A detailed examination demonstrated visuospatial and cognitive impairments. He required inpatient rehabilitation for three weeks, and outpatient rehabilitation for two months. By six months, he had returned to his pre-injury level of functioning, but was unable to resume driving.. We describe rehabilitation outcomes of delayed intracranial haemorrhage and mild traumatic brain injury, with diminishing disability over six months. In our case report, the complication of the delayed intracranial haemorrhage resulted in significant activity limitations and participation restrictions, which affected the clinical management, including the need for multidisciplinary rehabilitation. The risk of delayed intracranial haemorrhage in mild head injury remains a significant problem requiring further research.

Topics: Aged; Anticoagulants; Brain Injuries; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Male; Time Factors; Tomography, X-Ray Computed; Warfarin

Whether and when to resume oral anticoagulant therapy for patients who survive warfarin-related intracranial hemorrhage (ICH) remains a dilemma lacking consensus recommendations and high-quality evidence to guide clinical decision making.. To determine the incidences of recurrent ICH, thrombosis, and death in relation to resumption or non-resumption of warfarin therapy during the 365 days after incident ICH.. We conducted a retrospective cohort study of adult patients in an integrated healthcare delivery system who were receiving warfarin therapy at the time of incident (index) ICH between 1/1/2000 and 12/31/2007 and survived to hospital discharge. The primary outcomes were recurrent ICH, thrombosis (stroke, systemic embolism, and venous thromboembolism), and all-cause mortality during the 365 days following index ICH. Patients were assigned to one of two groups defined by warfarin therapy resumption after the index ICH.. There were 160 patients discharged from the hospital following warfarin-related index ICH; of these 54 (33.8%) resumed warfarin therapy and 106 (66.2%) did not. Recurrent ICH occurred in a numerically greater, but statistically non-significant, proportion of patients who did not resume warfarin therapy (7.6% vs. 3.7%, p=0.497). Similarly, patients who did not resume warfarin had a three-fold higher (12.3% vs. 3.7%, p=0.092) and approximately two-fold higher (31.1% vs. 18.5%, p=0.089) rates of thrombosis and all-cause mortality, respectively, during follow up.. Resumption of warfarin therapy following warfarin-associated ICH appeared not to be associated with increased risk of recurrent ICH but trended toward reduced thrombosis and all-cause mortality.

Topics: Aged; Anticoagulants; Female; Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Male; Risk; Venous Thromboembolism; Warfarin

Patients on anticoagulation are at increased risk for intracranial hemorrhage (ICH) after trauma. This is important for geriatric trauma patients, who are increasing in number, frequently fall, and often take anticoagulants. This study sought to evaluate whether prehospital use of dabigatran, a newer anticoagulant, is associated with outcome differences in geriatric trauma patients suffering falls when compared with warfarin. The registry of a Level II community trauma center was used to identify 247 patients aged 65 and older who sustained a fall while taking prehospital dabigatran or warfarin admitted between December 2010 and March 2014. Patients on warfarin were included if their International Normalized Ratio was therapeutic (2-3). About 176 of the 247 patients were then compared using coarsened exact matching. In the matched analysis, overall population means for age, Glasgow Coma Score, and Injury Severity Score were 83.5, 14.7, and 5.1, respectively. The overall rate of ICH was 12.5 per cent, with a mortality rate of 16.1 per cent for patients who sustained an ICH. There were no observed differences in ICH, hospital length of stay, intensive care unit length of stay, or mortality between patients taking prehospital warfarin or dabigatran.

Topics: Accidental Falls; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; California; Dabigatran; Female; Follow-Up Studies; Glasgow Coma Scale; Humans; Incidence; Intracranial Hemorrhages; Male; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Warfarin; Wounds and Injuries

Topics: Anticoagulants; Blood Coagulation Factors; Factor VII; Female; Humans; Intracranial Hemorrhages; Male; Neurosurgical Procedures; Plasma; Warfarin

Acetylsalicylic acid (ASA) and warfarin are used to prevent ischemic cerebrovascular events. They have serious complications including intracranial hemorrhages (ICHs). Warfarin-related intracerebral hemorrhage (ich) incidence is .2%-5% in population that accounts for 10%-12% of all ichs. In this article, we investigated the profile of ASA and warfarin-related spontaneous ICHs in comparison with ICHs without any drug use (WADU) with their clinical, radiological, and biochemical properties.. In all, 486 patients aged 18-101 years with spontaneous ICHs were included. Patients constituted 4 separate groups: users of warfarin, ASA, ASA + warfarin, and WADU. Clinical, neurological, etiological, and radiological data of these patients were compared.. There were 32 patients in warfarin, 58 patients in ASA, and 7 in warfarin + ASA group. Most of the patients were in no drug group (389 patients). The most frequent type of hemorrhage was supratentorial intraparenchymal hemorrhage. The most common accompanying disease was hypertension. The number of female patients was statistically significant in the warfarin group. Glasgow Coma Scale (GCS), accompanying diseases, opening of the hematoma to the ventricle, localization of the hemorrhage, age of the patient, and activated partial thromboplastin time level are all related to the outcome of patients. Warfarin users had worst mortality rate.. Use of warfarin, low GCS score, opening to ventricle, older age, accompanying diabetes, and/or hypertension were worse prognostic factors. It is possible that patients with these unfavorable prognostic factors cannot survive.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation; Comorbidity; Diabetes Mellitus; Female; Fibrinolytic Agents; Glasgow Coma Scale; Humans; Hypertension; Intracranial Hemorrhages; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Turkey; Warfarin; Young Adult

Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established.. This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions.. Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups.. A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.

Topics: Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Factor VIIa; Female; Hemostatics; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Warfarin

The most common indication for treatment with warfarin is the prevention of ischemic stroke in patients with atrial fibrillation. Time in therapeutic range (TTR) is an important tool to evaluate the quality of anticoagulation treatment. The aim of this study was to investigate the quality of treatment and the incidence of bleeding complications in patients on warfarin treatment treated by the anticoagulation clinic in Helsingborg. This is the first study that has specifically focused on the spontaneous reporting of bleeding complications in a real-world population. A total of 4,400 patients with a total of 8,394 patient years were registered, in the database Journalia AVK, during the time period November 1, 2007 to November 1, 2010. The mean age was 72 years. TTR was 73.3 % for the whole population. 421 patients suffered from haemorrhagic events. The frequency of major and fatal bleedings and intracranial haemorrhage (ICH) were 1.6, 0.2 and 0.5% per patient-year, respectively. A correlation between age and severe bleeding (major, fatal and ICH) (p = 0.003) was seen, but no correlation between gender and severe bleeding (p = 0.27). In 60 out of 455 bleeding events the complication had been reported to the anticoagulation clinic. At the anticoagulation clinic in Helsingborg the quality of warfarin treatment is good compared to previous results described in the literature, with regards to bleeding complications and efficacy. However, in our study, we confirm that the spontaneous reporting of bleeding complications related to warfarin is inadequate, and that review of patient records is needed to assure proper follow-up.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Prospective Studies; Registries; Retrospective Studies; Warfarin

Intracranial haemorrhage (ICH), which affects up to 1% of patients on oral anticoagulation per year, is the most feared and devastating complication of this treatment. After such an event, it is unclear whether anticoagulant therapy should be resumed. Such a decision hinges upon the assessment of the competing risks of haematoma growth or recurrent ICH and thromboembolic events. ICH location and the risk for ischaemic cerebrovascular event seem to be the key factors that lead to risk/benefit balance of restarting anticoagulation after ICH. Patients with lobar haemorrhage or cerebral amyloid angiopathy remain at higher risk for anticoagulant-related ICH recurrence than thromboembolic events and, therefore would be best managed without anticoagulants. Patients with deep hemispheric ICH and a baseline risk of ischemic stroke >6.5% per year, that corresponds to CHADS2≥ 4 or CHA2DS2-VASc ≥ 5, may receive net benefit from restarting anticoagulation. To date, a reasonable recommendation regarding time to resumption of anticoagulation therapy would be after 10 weeks. Available data regarding the role of magnetic resonance imaging in assessing the risks of both ICH and warfarin-related ICH do not support the use of this test for excluding anticoagulation in patients with atrial fibrillation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Brain; Cerebrovascular Circulation; Female; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Microcirculation; Middle Aged; Recurrence; Risk; Stroke; Thromboembolism; Warfarin

This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study.

Topics: Animals; Antithrombins; Benzimidazoles; beta-Alanine; Brain Ischemia; Dabigatran; Disease Models, Animal; Fibrinolytic Agents; Intracranial Hemorrhages; Male; Rats; Rats, Wistar; Stroke; Tissue Plasminogen Activator; Warfarin

Anticoagulation agents are proven risk factors for intracranial hemorrhage (ICH) in traumatic brain injury (TBI). The aim of our study is to describe the epidemiology of prehospital coumadin, aspirin, and Plavix (CAP) patients with ICH and evaluate the use of repeat head computed tomography (CT) in this group. We performed a retrospective study from our trauma registry. All patients with intracranial hemorrhage on initial CT with prehospital CAP therapy were included. Demographics, CT scan findings, number of repeat CT scans, progressive findings, and neurosurgical intervention were abstracted. A comparison between prehospital CAP and no-CAP patients was done using χ(2) and Mann-Whitney U test. A total of 1606 patients with blunt TBI charts were reviewed of whom 508 patients had intracranial bleeding on initial CT scan and 72 were on prehospital CAP therapy. CAP patients were older (P < 0.001), had higher Injury Severity Score and head Abbreviated Injury Scores on admission (P < 0.001), were more likely to present with an abnormal neurologic examination (P = 0.004), and had higher hospital and intensive care unit lengths of stay (P < 0.005). Eighty-four per cent of patients were on antiplatelet therapy and 27 per cent were on warfarin. The CAP patients have a threefold increase in the rate of worsening repeat head CT (26 vs 9%, P < 0.05). Prehospital CAP therapy is high risk for progression of bleeding on repeat head CT. Routine repeat head CT remains an important component in this patient population and can provide useful information.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Brain Injuries; Clopidogrel; Cohort Studies; Disease Progression; Female; Head Injuries, Closed; Humans; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Multivariate Analysis; Registries; Retrospective Studies; Risk Factors; Ticlopidine; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Female; Humans; Intracranial Hemorrhages; Male; Pyridines; Stroke; Warfarin

Acute limb ischemia (ALI) in pediatric patients is rare but may lead to limb loss and life-long complications. This study reviewed the experience of a Canadian tertiary pediatric center with the medical and operative management of ALI.. The medical records of inpatients diagnosed with ALI of the upper or lower limb between 1999 and 2012 were reviewed. Patient demographics, arterial clot site and etiology, intervention, anticoagulation type and duration, and short-term and long-term complications were analyzed.. A total of 151 patients (45% female) presented with signs of limb ischemia, of whom 38% were aged <30 days, 46% were between 1 and 12 months, and 16% were between 1 and 18 years. Ninety-four percent of those injuries involved the lower limbs. Ninety-one percent were due to vessel catheterization, 5% were idiopathic, 1% were congenital, and 4% traumatic. Ninety-four percent were managed nonoperatively. Patients were treated with a combination of thrombolysis, unfractionated or low-molecular-weight heparin, aspirin or warfarin, or both (duration, 1 day-13 years). All patients were monitored after discharge at our institution or at their referring hospital (average, 3.4 ± 2.8 years). Fifteen percent had complications related to ALI or anticoagulation (most commonly limb length or thigh circumference discrepancy, or intracranial hemorrhage). Nineteen percent of patients died of unrelated causes (sepsis, multiorgan dysfunction, or cardiac failure).. In contrast with adults, ALI in children can generally be managed nonoperatively with anticoagulation, likely because of their greater ability to develop arterial collaterals. Long-term follow-up by a multidisciplinary team of pediatric and surgical specialists and allied health professionals is integral to achieving a successful outcome in children with ALI.

Topics: Acute Disease; Adolescent; Anticoagulants; Aspirin; Canada; Catheterization, Peripheral; Child; Child, Preschool; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Hospitals, Pediatric; Humans; Infant; Intracranial Hemorrhages; Ischemia; Lower Extremity; Male; Organ Size; Retrospective Studies; Tertiary Care Centers; Upper Extremity; Warfarin

There are no studies demonstrating that prothrombin complex concentrates (PCC) improves outcome compared FFP in patients with warfarin-associated intracranial hemorrhage.. A prospective, observational study was conducted of patients who received PCC (Bebulin VH), FFP, or PCC + FFP. All groups received vitamin K 10 mg IV. INR reversal (<1.4), adverse events (venous thromboembolism, myocardial infraction, pulmonary edema), major hemorrhage (new or worsened intracranial hemorrhage, anemia requiring transfusion or GI bleed), and 3-month functional outcome were compared between the groups using Chi squared and logistic regression analysis.. Of 64 patients, PCC alone was used in 16 (mean dose 48 IU/kg), FFP alone in 25 (mean dose 12.5 ml/kg), and PCC + FFP in 23 (median doses 47.4 IU/kg and 11.4 ml/kg, respectively). INR correction occurred in 88, 84, and 70 %, respectively. There were no differences in time to INR correction or adverse events between the groups, but FFP alone was associated with more major hemorrhage after administration (52 %, OR 5.0, 95 % CI 1.6-15.4, P = 0.006) and PCC with less (6 %, OR 0.1, 95 % CI 0.01-0.8, P = 0.033). After adjusting for age, admission GCS, initial INR, and bleed type, the use of PCC was associated with a lower risk of death or severe disability at 3-months (adjusted OR 0.02, 95 % CI 0.001-0.8, P = 0.039), while FFP alone was associated with a higher risk (adjusted OR 51.6, 95 % CI 1.2-2163.1, P = 0.039).. PCC adequately corrected INR without any increase in adverse events compared to FFP and was associated with less major hemorrhage and improved 3-month outcomes in patients with warfarin-associated intracranial hemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Arteriovenous Malformations; Aspirin; Drug Therapy, Combination; Fatal Outcome; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stents; Thiophenes; Thrombosis; Warfarin

Data regarding use of prothrombin complex concentrate (PCC) for international normalization ratio (INR) reversal in warfarin-associated intracranial hemorrhage (wICH) is variable with regards to dosages, adjunctive agents, and product choice. In 2012, we implemented a fixed, weight-based [30 IU/kg] dosing protocol of 3-factor PCC (3PCC) utilizing a rapid infusion rate and no requirement for fresh frozen plasma (FFP) following factor product administration. We aimed to evaluate the impact of this protocol on immediate and delayed INR reversal in patients admitted with wICH in the absence of FFP co-administration.. We conducted a retrospective review of patients receiving 3PCC following wICH between January 1, 2012 and December 10, 2013. The primary objective was to determine the percentage of patients achieving goal INR (≤1.4) following 3PCC administration. Patients were excluded if their bleed was not intracranial in origin, received a dose outside of the specified protocol, or were given FFP as an adjunctive agent.. We included 35 patients with a mean presenting INR of 3.2 ± 1.3. Thirty patients (85.7%) achieved goal INR (≤1.4) following one dose of 3PCC. The mean INR after infusion of 3PCC was 1.3 ± 0.2. The median duration between 3PCC infusion and subsequent INR was 48.0 min (30-70.1 min). Vitamin K was utilized in 33 (94.3%) patients. No patient experienced a thromboembolic event within 7 days of 3PCC administration.. Fixed, weight-based dosing of 3PCC without adjunctive FFP resulted in high rates of complete INR reversal without significant adverse events.

Topics: Aged; Blood Coagulation Factors; Clinical Protocols; Drug Dosage Calculations; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Treatment Outcome; Warfarin

Warfarin therapy increases the incidence intracranial hemorrhage (ICH), especially in the geriatric population. Timely reversal of international normalized ratio (INR) is integral in the management of these patients for whom fresh frozen plasma (FFP) with vitamin K is the standard of treatment. We hypothesized that implementing a protocol that used prothrombin complex concentrate (PCC) would reverse INR values more swiftly and decrease the amount of FFP administered. In November 2011, a protocol was implemented for administering PCC to the geriatric population on warfarin admitted for life-threatening bleeds. These patients received 25 IU/kg ideal body weight of a three-factor PCC (Profilnine SD) if their INR was over 1.5 or greater. FFP was given if follow-up INR revealed an INR of 1.5 or greater. Retrospectively the data from 29 patients who received PCC were compared with a historical control group of 34 patients. Protocol use resulted in a significantly faster INR reversal (PCC: 151.6 ± 84.3 minutes vs control: 485.0 ± 321 minutes; P < 0.001), time to achieve an INR less than 1.5 (PCC: 484 ± 242 minutes vs control: 971 ± 1208 minutes; P = 0.036), and less FFP administered (PCC: 1.3 ± 1.0 vs control:3.3 ± 1.5; P < 0.001). PCC patients had a decreased incidence of progression of their ICH (PCC: 17.2% vs control: 44.2%; P = 0.031). Rapid reversal of coagulopathy in geriatric patients on warfarin is vital to limit the extent of ICH. PCC allows a much more rapid reversal than standard treatment with only FFP and vitamin K. Adopting such a protocol is associated not only with a more rapid reversal and less FFP use, but also less patients went on to extend their head bleeds.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Craniocerebral Trauma; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Pennsylvania; Retrospective Studies; Trauma Centers; Warfarin

The increased risk of hemorrhage associated with anticoagulant therapy following traumatic brain injury creates a serious dilemma for medical management of older patients: Should anticoagulant therapy be resumed after traumatic brain injury, and if so, when?. To estimate the risk of thrombotic and hemorrhagic events associated with warfarin therapy resumption following traumatic brain injury.. Retrospective analysis of administrative claims data for Medicare beneficiaries aged at least 65 years hospitalized for traumatic brain injury during 2006 through 2009 who received warfarin in the month prior to injury (n = 10,782).. Warfarin use in each 30-day period following discharge after hospitalization for traumatic brain injury.. The primary outcomes were hemorrhagic and thrombotic events following discharge after hospitalization for traumatic brain injury. Hemorrhagic events were defined on inpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification codes and included hemorrhagic stroke, upper gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and myocardial infarction. A composite of hemorrhagic or ischemic stroke was a secondary outcome.. Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0.72-0.96]).. Results from this study suggest that despite increased risk of hemorrhage, there is a net benefit for most patients receiving anticoagulation therapy, in terms of a reduction in risk of stroke, from warfarin therapy resumption following discharge after hospitalization for traumatic brain injury.

Topics: Adrenal Gland Diseases; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Injuries; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Stroke; Thrombosis; Venous Thrombosis; Warfarin

Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p=0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p<0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p<0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.

Topics: Anticoagulants; Antidotes; Blood Coagulation Factors; Brain Injuries; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Plasma; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Spinal Diseases; Subarachnoid Hemorrhage; Tertiary Care Centers; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Humans; Intracranial Hemorrhages; Male; Plasma; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Humans; Intracranial Hemorrhages; Male; Plasma; Warfarin

In randomized trials, patients with atrial fibrillation (AF) receiving dabigatran, a direct oral anticoagulant, had lower risk of intracranial bleeding (ICB) than those on warfarin. However, concerns exist about potential worse outcomes in dabigatran users if bleeding occurs, given the lack of approved reversal agents. Thus, we examined in-hospital mortality in AF patients with ICB being treated with dabigatran versus warfarin in a real-world population in the United States.. We analyzed healthcare utilization claims in the Truven Health Marketscan Research Databases. The study sample included patients with AF admitted to a hospital with a primary diagnosis of ICB. Information on medications, inpatient, and outpatient diagnoses was obtained from available claims. Propensity score-adjusted risk ratios and 95% confidence intervals of in-hospital mortality comparing current users of dabigatran versus warfarin were estimated using relative risk regression.. Among 2391 AF patients admitted with ICB (2290 on warfarin, 101 on dabigatran), 531 died during their admission. In-hospital mortality was similar in those treated with warfarin (22%) or dabigatran (20%). Compared with warfarin users, the propensity score-adjusted risk ratio (95% confidence interval) of mortality in dabigatran users was 0.93 (0.62-1.37). Associations were similar across different ICB subtypes (intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hematoma).. In this sample of AF patients with ICB on oral anticoagulants, dabigatran was not associated with higher in-hospital mortality compared with warfarin. Hence, reluctance to use dabigatran because of a lack of approved reversal agents is not supported by our results.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Hospital Mortality; Humans; Intracranial Hemorrhages; Male; Odds Ratio; Retrospective Studies; Warfarin

What is the prevalence of immediate and incidence of delayed intracranial hemorrhage in patients with blunt head trauma who use warfarin or clopidogrel?. Nishijima DK, Offerman SR, Ballard DW, et al. Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and preinjury warfarin or clopidogrel use. Ann Emerg Med 2012;59:460-8.e7.. To assess the prevalence of immediate and the cumulative incidence of delayed traumatic intracranial hemorrhage in patients using warfarin or clopidogrel.

Topics: Anticoagulants; Craniocerebral Trauma; Female; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Clinical trial data suggest that dabigatran and warfarin have similar rates of major bleeding but higher rates of gastrointestinal bleeding. These findings have not been evaluated outside of a clinical trial. We evaluated the relative risks of any, gastrointestinal, intracranial, and other bleeding for Veterans Affairs patients who switched to dabigatran after at least 6 months on warfarin, compared with patients who continued on warfarin.. We used national Veterans Affairs administrative encounter and pharmacy data from fiscal years 2010-2012 to identify 85,344 patients with atrial fibrillation who had been taking warfarin for at least 180 days before June 2011, of whom 1394 (1.7%) received dabigatran (150 mg) during the next 15 months. Dates of the first occurrence of each type of bleed and dates of death from June 2011 to September 2012 were determined. Baseline and time-dependent patient characteristics were identified, including comorbid conditions, stroke and bleeding risk scores, and time in therapeutic range for international normalized ratios. Marginal structural models were used to address selection bias in the longitudinal observational data. Weighted logistic regression models were fit using generalized estimating equations and reflected baseline and time-dependent covariates and weekly indicators of anticoagulant type (warfarin or dabigatran).. Compared with patients who never used dabigatran, patients who used dabigatran at least once were younger, were more likely to be white, had lower international normalized ratio time in therapeutic range on warfarin, had lower stroke risk scores, and had similar bleeding risk scores. Overall, 10,734 patients experienced bleeding events, including 131 events after dabigatran use. The risk-adjusted rate of any bleeding was higher with dabigatran compared with warfarin, which was largely driven by a 54% higher risk of gastrointestinal bleeding with dabigatran. Rates of intracranial, other bleeding, and death were similar for dabigatran and warfarin.. Dabigatran may increase the likelihood of gastrointestinal bleeds.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Drug Substitution; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Stroke; United States; United States Department of Veterans Affairs; Warfarin

Elderly Americans are at increased risk of head trauma, particularly fall related. The effect of warfarin on head trauma outcomes remains controversial.. Medicare beneficiaries with head injuries from 2009 to 2011 were identified by International Classification of Diseases (ICD)-9 code. Preinjury warfarin use was determined using Part D claims. Multiple logistic regression models determined the association of preinjury warfarin on need for hospitalization, intensive care unit care, and occurrence of intracranial hemorrhage. Association between warfarin and in-hospital mortality was assessed using a Cox proportional hazard model.. Of 11,078 head injured patients, 5.2% were injured while on warfarin. Preinjury warfarin increased the odds of intracranial hemorrhage by 40% and doubled the risk of 30-day in-hospital mortality after adjusting for demographic and clinical factors.. Warfarin at the time of head injury increases the risk of adverse outcomes in Medicare beneficiaries with head injuries. Caution should be used when initiating anticoagulation in elderly Americans at risk for trauma.

Topics: Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Female; Follow-Up Studies; Humans; Incidence; Inpatients; Insurance Benefits; Intensive Care Units; Intracranial Hemorrhages; Male; Medicare; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate; Thromboembolism; United States; Warfarin

The impact of correcting elevated International Normalized Ratio (INR) values on inhospital mortality in patients with warfarin-associated major bleeding is presented.. Using patient information from the database of a large U.S. health system, a retrospective analysis was conducted to (1) evaluate inpatient practice patterns in correcting INR elevations among patients hospitalized with warfarin-related intracranial hemorrhage (ICH) or non-ICH bleeding and (2) test the hypothesis that achieving INR correction, defined as an INR of ≤1.5, at any point during the hospital stay is correlated with lower inhospital mortality. Cox proportional hazards models were constructed to assess predictors of inhospital death.. Among the 354 patients who met the study selection criteria, INR correction was achieved in 87.9% overall (92.5% and 85.5% of patients with ICH and non-ICH bleeds, respectively). Patients whose elevated INR values were corrected had significantly lower inhospital death rates than those with uncorrected elevations: 15.3% versus 55.6% (p = 0.010) among patients with ICH and 2.0% versus 11.8% (p = 0.017) among those with non-ICH bleeds. After adjusting for baseline demographics and comorbidities, the correlation between failure to correct INR elevations and increased mortality risk was significant only for patients with ICH (hazard ratio, 8.04; 95% confidence interval, 2.07-31.18; p = 0.003).. Results of this study indicated that correction of elevated INR values was associated with a lower likelihood of inhospital death among warfarin-treated patients hospitalized for ICH or non-ICH major bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Component Transfusion; Databases, Factual; Female; Hemorrhage; Hospital Mortality; Humans; International Normalized Ratio; Intracranial Hemorrhages; Length of Stay; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; United States; Warfarin

Antiplatelet and anticoagulant medication increases the risk of intracranial hemorrhage (ICH) after a fall in geriatric patients. We sought to determine whether there were differences in ICH rates and outcomes based on type of anticoagulant or antiplatelet agent after a ground-level fall (GLF). Our institutional trauma registry was used to identify patients 65 years old or older after a GLF while taking warfarin, clopidogrel, or aspirin over a 2-year period. Rates and types of ICH and patient outcomes were evaluated. Of 562 patients who met inclusion and exclusion criteria, 218 (38.8%) were on warfarin, 95 (16.9%) were on clopidogrel, and 249 (44.3%) were on aspirin. Overall ICH frequency was 15 per cent with no difference in ICH rate, type of ICH, need for craniotomy, mortality, or intensive care unit or hospital length of stay between groups. Patients with ICH were more likely to present with abnormal Glasgow Coma Score, history of hypertension, and/or loss of consciousness.

Topics: Accidental Falls; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Female; Humans; Intracranial Hemorrhages; Logistic Models; Male; Multivariate Analysis; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Ticlopidine; Warfarin

A 75-year-old man with paroxysmal atrial fibrillation developed a traumatic intracranial hemorrhage during warfarin treatment. The administration of warfarin was stopped and rivaroxaban therapy, a novel oral anticoagulant (NOAC), was started. Immediately, his platelet count decreased to 3.7×10(4) /μL. The platelet count recovered rapidly after cessation of rivaroxaban administration. Development of thrombocytopenia and its rapid recovery was observed again after another administration, and subsequent cessation, of the drug. A diagnosis of rivaroxaban-induced thrombocytopenia was made. The incidence of thrombocytopenia due to NOACs is rare. Careful attention to thrombocytopenia, which is associated with a higher risk for life-threatening bleeding, is therefore necessary during treatment with NOACs.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Male; Morpholines; Rivaroxaban; Stroke; Thiophenes; Thrombocytopenia; Warfarin

To compare the safety and effectiveness of three methods of reversing coagulopathic effects of warfarin in patients with potentially life-threatening intracranial hemorrhage.. A retrospective electronic medical record review of 63 patients with warfarin-related intracranial hemorrhage between 2007 and 2010 in an integrated health care delivery system was conducted. The three methods of rapid warfarin reversal were fresh-frozen plasma (FFP), activated factor VII (FVIIa; NovoSevenRT [Novo Nordisk, Bagsværd, Denmark]), and prothrombin complex concentrate (PCC; BebulinVH [Baxter, Westlake Village, California, USA], ProfilnineSD [Grifols, North Carolina, USA]), each used adjunctively with vitamin K (Vit K, phytonadione). We determined times from reversal agent order to laboratory evidence of warfarin reversal (international normalized ratio [INR]) in the first 48 hours and compared INR rebound rates and complications in the first 48 hours.. Reversal with FFP took more than twice as long compared with FVIIa or PCC. To reach an INR of 1.3, mean (±SD) reversal times were 1933 ± 905 minutes for FFP, 784 ± 926 minutes for FVIIa, and 980 ± 1021 minutes for PCC (P < 0.001; P < 0.01 between FFP and FVIIa, P < 0.05 between FFP and PCC). INR rebound occurred in 0 of 31 patients for FFP, 4 of 8 for FVIIa, and 0 of 7 for PCC (P = 0.001). Complications were uncommon. FVIIa was 15 and 3.5 times as expensive as FFP and PCC, respectively.. As an adjunct to Vit K for rapid warfarin reversal, FVIIa and PCC appear more effective than FFP. Either FVIIa or PCC are reasonable options for reversal, but FVIIa is considerably more expensive and may have greater risk of INR rebound.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Electronic Health Records; Emergency Medical Services; Factor VII; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Recombinant Proteins; Retrospective Studies; Vitamin K; Warfarin

Topics: Anticoagulants; Blood Coagulation Factors; Factor VII; Female; Humans; Intracranial Hemorrhages; Male; Neurosurgical Procedures; Plasma; Warfarin

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration; Warfarin

The aim of this study was to assess the efficacy and safety in an "everyday clinical practice" population of anticoagulant-naïve patients with atrial fibrillation (AF) treated with dabigatran etexilate after its post-approval availability in Denmark, compared with warfarin.. Concerns have been raised about an excess of bleeding events or myocardial infarction (MI) among patients treated with the new oral direct thrombin inhibitor, dabigatran etexilate.. From the Danish Registry of Medicinal Product Statistics, we identified a dabigatran-treated group and a 1:2 propensity-matched warfarin-treated group of 4,978 and 8,936, respectively. Comparisons on efficacy and safety outcomes were made on the basis of Cox-proportional hazards models stratified on propensity-matched groups.. Stroke and systemic embolism were not significantly different between warfarin- and dabigatran-treated patients. Adjusted mortality was significantly lower with both dabigatran doses (110 mg b.i.d., propensity-match group stratified hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.65 to 0.95; 150 mg b.i.d., aHR: 0.57, 95% CI: 0.40 to 0.80), when compared with warfarin. Pulmonary embolism was lower compared with warfarin for both doses of dabigatran. Less intracranial bleeding was seen with both dabigatran doses (110 mg b.i.d., aHR: 0.24, 95% CI: 0.08 to 0.56; 150 mg b.i.d., aHR: 0.08, 95% CI: 0.01 to 0.40). The incidence of MI was lower with both dabigatran doses (110 mg b.i.d., aHR: 0.30, 95% CI: 0.18 to 0.49; 150 mg b.i.d., aHR: 0.40, 95% CI: 0.21 to 0.70). Gastrointestinal bleeding was lower with dabigatran 110 mg b.i.d. (aHR: 0.60, 95% CI: 0.37 to 0.93) compared with warfarin but not dabigatran 150 mg b.i.d. The main findings were broadly consistent in a subgroup analysis of dabigatran users with ≥1-year follow-up (median follow-up 13.9 months [interquartile range: 12.6 to 15.3 months]).. In this "everyday clinical practice" post-approval nationwide clinical cohort, there were similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Mortality, intracranial bleeding, pulmonary embolism, and MI were lower with dabigatran, compared with warfarin. We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with ≥1-year follow-up.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; Dabigatran; Denmark; Dose-Response Relationship, Drug; Drug Prescriptions; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hospitalization; Humans; Incidence; Intracranial Hemorrhages; Logistic Models; Male; Myocardial Infarction; Propensity Score; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Pyridines; Registries; Stroke; Warfarin

To investigate the relationship between hemorrhagic stroke and use of antiplatelets and warfarin using data from The Health Improvement Network.. A total of 1,797 incident cases of intracerebral hemorrhage (ICH) and 1,340 of subarachnoid hemorrhage (SAH) were ascertained. Density-based sampling was used to select 10,000 controls free from hemorrhagic stroke. Risk of hemorrhagic stroke was evaluated in current users and nonusers of antiplatelets and warfarin. Unconditional logistic regression models were used to adjust for age, sex, calendar year, alcohol, body mass index, hypertension, and health services utilization.. Aspirin use was not associated with an increased risk of ICH (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.93-1.21), but was associated with a decreased risk of SAH (OR 0.82, 95% CI 0.67-1.00), compared with no therapy. Aspirin use ≥3 years was associated with a decreased risk of SAH (OR 0.63, 95% CI 0.45-0.90) compared with no therapy. Warfarin use was associated with a greatly increased risk of ICH (OR 2.82, 95% CI 2.26-3.53) and a moderately increased risk of SAH (OR 1.67, 95% CI 1.15-2.43) compared with no therapy. International normalized ratio values ≥3 carried a marked risk of ICH (OR 7.01, 95% CI 4.10-11.99).. Aspirin is not associated with a risk of ICH compared with no therapy. Chronic low-dose aspirin treatment may have a protective effect on the risk of SAH. Warfarin users in this study cohort were at a much higher risk of ICH than those receiving no therapy, with a marked association with international normalized ratio >3.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Case-Control Studies; Cohort Studies; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Male; Middle Aged; Population Surveillance; Risk Factors; Stroke; Warfarin; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Female; Humans; Intracranial Hemorrhages; Male; Pyridines; Stroke; Warfarin

Topics: Aged; Aged, 80 and over; Aging; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; Intracranial Hemorrhages; Stroke; Warfarin

There are well defined indications in which chronic anticoagulant treatment has been widely applied. However, complications of this therapy are less discussed, although these complications may lead to serious or even fatal consequences.. The aim of the authors was to analyze data of patients admitted to their multidisciplinary intensive care unit for complications of chronic anticoagulant therapy between January 1, 2006 and December 31, 2011.. Data of 73 patients admitted for serious hemorrhagic complications of chronic anticoagulant therapy were retrospectively analysed.. Of the 73 patients, 63 patients had intracranial bleeding, most of them with traumatic origin. A few patients with other hemorrhagic complications such as spinal hematoma, gastrointestinal bleeding, hemorrhagic cystitis, hemothorax and intraabdominal bleeding were also noted. The INR values were out of therapeutic range in 43 patients. The mortality of patients was very high in spite of complex intensive care; 49 of the 73 patients (75.5%) died due to hemorrhagic complications.. Due to the high proportion of traumatic origin, the large number of out-of-range INR, and the high mortality, the authors strongly believe that regular patient follow-up, transmission of detailed information, and time-to-time reevaluation of the indications and contraindications of chronic anticoagulant therapy could help to decrease the number of serious and fatal complications of chronic anticoagulant therapy.. Bevezetés: A krónikus antikoaguláns kezelést jól körülhatárolt indikációs körrel, széles körben alkalmazzák. Kevesebb szó esik azonban az általa okozott vérzéses szövődményekről, amelyek súlyosak vagy akár halálos kimenetelűek is lehetnek. Célkitűzés: A Szent János Kórház és Észak-budai Egyesített Kórházak Központi Aneszteziológiai és Intenzív Terápiás Osztályán 2006. január 1. és 2011. december 31. között krónikus antikoaguláns kezelés kapcsán kialakult vérzéses szövődményes esetek elemzése. Módszer: A szerzők multidiszciplináris intenzív osztályán a vizsgált hat év alatt összesen 73 betegnél fordult elő intenzív ellátást igénylő vérzéses szövődmény krónikus antikoagulálás kapcsán. Eredmények: Hatvanhárom esetben intracranialis vérzést észleltek, ezen belül leggyakrabban traumás eredetűt. Kisebb számban előfordult még spinalis haematoma, gastrointestinalis vérzés, haemorrhagiás cystitis, haemothorax és hasüregi vérzés. A betegek felvételi INR-értéke 43 esetben a terápiás tartományon kívül esett. A betegek mortalitása igen magas volt, a komplex intenzív kezelés ellenére 49 beteg halt meg a vérzéssel összefüggésben (75,5%). Következtetések: A gyakori traumás eredetre, a terápiás tartományon kívül eső INR-értékek nagy számára és a magas mortalitásra tekintettel a szerzők véleménye szerint rendszeres betegkövetéssel, részletes felvilágosítással, a társbetegségek alakulásával párhuzamosan revideált indikáció/kontraindikáció alapján folytatott krónikus antikoaguláns kezeléssel a vérzéses szövődmények száma csökkenthető lenne. Orv. Hetil., 2013, 154(46), 1829–1835.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Critical Care; Cystitis; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hemothorax; Humans; Hungary; Intensive Care Units; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Warfarin

Avoiding intracranial hemorrhage (ICH) during warfarin therapy is critical but little is known about factors that affect warfarin-related ICH outcomes. We aimed to define the impact of warfarin on ICH incidence rates and to identify baseline clinical characteristics of patients who experienced ICH and factors associated with fatal ICH.. The primary outcome of this retrospective cohort study was the incident ICH rate per 10,000 person-years for patients receiving and not receiving warfarin therapy. Cox proportional hazards modeling was used to adjust for potential confounding factors in assessment of the association of warfarin with fatal ICH.. A total of 1348 patients with incident ICH, 259 (19%) who were receiving warfarin therapy, were included. The incident ICH rates were 74/10,000 (warfarin) and 5/10,000 (non-warfarin) person-years (p<0.001). Warfarin patients were older and carried a higher burden of chronic disease. The unadjusted hazard ratio (HR) for fatal ICH was 1.64 (95% confidence interval [CI] 1.31-2.05) for warfarin patients compared to non-warfarin patients. However, the HR was no longer significant after adjustment for confounding variables (1.10; 95% CI 0.84-1.42). An INR greater than 3.5 at presentation doubled the adjusted risk for fatal ICH with warfarin therapy. Subarachnoid and subdural ICHs were less likely to be fatal than other ICH types, and each year increase in age was associated with 4% increased risk of fatal ICH.. Although warfarin use increases the rate of incident ICH, other factors impact the risk of fatal ICH, even among anticoagulated patients.

Topics: Aged; Anticoagulants; Cohort Studies; Colorado; Female; Humans; Incidence; Intracranial Hemorrhages; Logistic Models; Male; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Warfarin

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH). This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine(®) SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded. The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2-3.3) and post-treatment INR was 1.4 (IQR 1.3-1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50-140) min. No patient's INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC. A 3-factor PCC preparation (Profilnine(®) SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.

Topics: Aged; Aged, 80 and over; Algorithms; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Hemostatics; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Humans; Intracranial Hemorrhages; Stroke; Thrombolytic Therapy; Warfarin

Topics: Anticoagulants; Craniocerebral Trauma; Female; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Topics: Anticoagulants; Craniocerebral Trauma; Female; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; Intracranial Hemorrhages; Medicare; Stroke; United States; Warfarin

The number of patients who are on long-term anticoagulation therapy while experiencing traumatic brain injury (TBI) is rising. This experimental study evaluated whether warfarin pre-treatment increases brain hemorrhage and worsens functional outcome after TBI, and whether the rapid reversal of anticoagulation after TBI prevents warfarin-exacerbated brain damage. Normal CD-1 mice (C) and mice pre-treated with warfarin (W) to an International Normalized Ratio of 3.5±0.9 underwent TBI using a controlled cortical impact model. Mean hemorrhage volume 24 h after TBI was 1.2±0.4 μL in C mice and 10.9±6.9 μL in W mice (p=0.029, n=4 per group). In a second study, anticoagulated mice received either saline (W-S) or prothrombin complex concentrate (W-PCC, 100 U/kg) intravenously 60 min after TBI. Anticoagulation reversal using PCC (W-PCC mice) reduced hemorrhage volumes as compared to W-S animals (7.3±6.0 versus 19.8±14.0 μL, p=0.045, n=8 per group). In a third study, we examined motor deficits and lesion volume in C, W-S, and W-PCC mice until 33 days after injury. Functional outcome and lesion volume were no different between groups (n=10 per group). In conclusion, we characterized an experimental model of TBI occurring during warfarin anticoagulation. Anticoagulation led to higher intracerebral blood volumes, but did not significantly worsen functional outcome. The rapid reversal of anticoagulation may be effective in preventing excess bleeding.

Topics: Animals; Anticoagulants; Brain Injuries; Disease Models, Animal; Hemorrhage; Intracranial Hemorrhages; Male; Mice; Recovery of Function; Warfarin

The concept of net clinical benefit has been used to quantify the balance between risk of ischaemic stroke (IS) and risk of intracranial haemorrhage (ICH) with the use oral anticoagulant therapy (OAC) in the setting of non-valvular atrial fibrillation (AF), and has shown that patients at highest risk of stroke and thromboembolism gain the greatest benefit from OAC with warfarin. There are no data for the new OACs, that is, dabigatran, rivaroxaban and apixaban, as yet. We calculated the net clinical benefit balancing IS against ICH using data from the Danish National Patient Registry on patients with non-valvular AF between 1997-2008, for dabigatran, rivaroxaban and apixaban on the basis of recent clinical trial outcome data for these new OACs. In patients with CHADS(2)=0 but at high bleeding risk, apixaban and dabigatran 110 mg bid had a positive net clinical benefit. At CHA(2)DS(2)-VASc=1, apixaban and both doses of dabigatran (110 mg and 150 mg bid) had a positive net clinical benefit. In patients with CHADS(2) score≥1 or CHA(2)DS(2)-VASc≥2, the three new OACs (dabigatran, rivaroxaban and apixaban) appear superior to warfarin for net clinical benefit, regardless of risk of bleeding. When risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit than warfarin. In the absence of head-to-head trials for these new OACs, our analysis may help inform decision making processes when all these new OACs become available to clinicians for stroke prevention in AF. Using 'real world' data, our modelling analysis has shown that when the risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit compared to warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Cohort Studies; Computer Simulation; Dabigatran; Decision Making, Computer-Assisted; Denmark; Humans; Intracranial Hemorrhages; Morpholines; Population Groups; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

Patients receiving warfarin who experience minor head injury are at risk of intracranial hemorrhage, and optimal management after a single head computed tomography (CT) scan is unclear. We evaluate a protocol of 24-hour observation followed by a second head CT scan.. In this prospective case series, we enrolled consecutive patients receiving warfarin and showing no intracranial lesions on a first CT scan after minor head injury treated at a Level II trauma center. We implemented a structured clinical pathway, including 24-hour observation and a CT scan performed before discharge. We then evaluated the frequency of death, admission, neurosurgery, and delayed intracranial hemorrhage.. We enrolled and observed 97 consecutive patients. Ten refused the second CT scan and were well during 30-day follow-up. Repeated CT scanning in the remaining 87 patients revealed a new hemorrhage lesion in 5 (6%), with 3 subsequently hospitalized and 1 receiving craniotomy. Two patients discharged after completing the study protocol with 2 negative CT scan results were admitted 2 and 8 days later with symptomatic subdural hematomas; neither received surgery. Two of the 5 patients with delayed bleeding at 24 hours had an initial international normalized ratio greater than 3.0, as did both patients with delayed bleeding beyond 24 hours. The relative risk of delayed hemorrhage with an initial international normalized ratio greater than 3.0 was 14 (95% confidence interval 4 to 49).. For patients receiving warfarin who experience minor head injury and have a negative initial head CT scan result, a protocol of 24-hour observation followed by a second CT scan will identify most occurrences of delayed bleeding. An initial international normalized ratio greater than 3 suggests higher risk.

Topics: Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Critical Pathways; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Prospective Studies; Time Factors; Tomography, X-Ray Computed; Trauma Centers; Warfarin; Watchful Waiting

This study assessed the frequency and factors associated with failure to correct international normalised ratio (INR) in patients administered fresh frozen plasma (FFP) for warfarin-related major bleeding. This retrospective database analysis used electronic health records from an integrated health system. Patients who received FFP between 01/01/2004 and 01/31/2010, and who met the following criteria were selected: major haemorrhage diagnosis the day before to the day after initial FFP administration; INR ≥2 on the day before or the day of FFP and another INR result available; warfarin prescription within 90 days. INR correction (defined as INR ≤1.3) was evaluated at the last available test up to one day following FFP. A total of 414 patients met selection criteria (mean age 75 years, 53% male, mean Charlson score 2.5). Patients presented with gastrointestinal bleeding (58%), intracranial haemorrhage (38%) and other bleed types (4%). The INR of 67% of patients remained uncorrected at the last available test up to one day following receipt of FFP. In logistic regression analysis, the INR of patients who were older, those with a Charlson score of 4 or greater, and those with non-ICH bleeds (odds ratio vs. intracranial bleeding 0.48; 95% confidence interval 0.31-0.76) were more likely to remain uncorrected within one day following FFP administration. In an alternative definition of correction, (INR ≤1.5), 39% of patients' INRs remained uncorrected. For a substantial proportion of patients, the INRs remain inadequately or uncorrected following FFP administration, with estimates varying depending on the INR threshold used.

Topics: Aged; Aged, 80 and over; Anticoagulants; Emergency Medicine; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Medical Records Systems, Computerized; Odds Ratio; Plasma; Regression Analysis; Retrospective Studies; Warfarin

Anticoagulant-associated intracranial hemorrhage (aaICH) presents with larger hematoma volumes, higher risk of hematoma expansion, and worse outcome than spontaneous intracranial hemorrhage. Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of anticoagulation after aaICH. Given the lack of randomized controlled trial evidence of efficacy, and the potential for thrombotic complications, we aimed to determine outcomes in patients with aaICH treated with PCC.. We conducted a prospective multicenter registry of patients treated with PCC for aaICH in Canada. Patients were identified by local blood banks after the release of PCC. A chart review abstracted clinical, imaging, and laboratory data, including thrombotic events after therapy. Hematoma volumes were measured on brain CT scans and primary outcomes were modified Rankin Scale at discharge and in-hospital mortality.. Between 2008 and 2010, 141 patients received PCC for aaICH (71 intraparenchymal hemorrhages). The median age was 78 years (interquartile range, 14), 59.6% were male, and median Glasgow Coma Scale was 14. Median international normalized ratio was 2.6 (interquartile range, 2.0) and median parenchymal hematoma volume was 15.8 mL (interquartile range, 31.8). Median post-PCC therapy international normalized ratio was 1.4: 79.5% of patients had international normalized ratio correction (<1.5) within 1 hour of PCC therapy. Patients with intraparenchymal hemorrhage had an in-hospital mortality rate of 42.3% with median modified Rankin Scale of 5. Significant hematoma expansion occurred in 45.5%. There were 3 confirmed thrombotic complications within 7 days of PCC therapy.. PCC therapy rapidly corrected international normalized ratio in the majority of patients, yet mortality and morbidity rates remained high. Rapid international normalized ratio correction alone may not be sufficient to alter prognosis after aaICH.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Hospital Mortality; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Prognosis; Prospective Studies; Registries; Warfarin

Topics: Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Intracranial Hemorrhages; Male; Warfarin

Patients receiving warfarin or clopidogrel are considered at increased risk for traumatic intracranial hemorrhage after blunt head trauma. The prevalence of immediate traumatic intracranial hemorrhage and the cumulative incidence of delayed traumatic intracranial hemorrhage in these patients, however, are unknown. The objective of this study is to address these gaps in knowledge.. A prospective, observational study at 2 trauma centers and 4 community hospitals enrolled emergency department (ED) patients with blunt head trauma and preinjury warfarin or clopidogrel use from April 2009 through January 2011. Patients were followed for 2 weeks. The prevalence of immediate traumatic intracranial hemorrhage and the cumulative incidence of delayed traumatic intracranial hemorrhage were calculated from patients who received initial cranial computed tomography (CT) in the ED. Delayed traumatic intracranial hemorrhage was defined as traumatic intracranial hemorrhage within 2 weeks after an initially normal CT scan result and in the absence of repeated head trauma.. A total of 1,064 patients were enrolled (768 warfarin patients [72.2%] and 296 clopidogrel patients [27.8%]). There were 364 patients (34.2%) from Level I or II trauma centers and 700 patients (65.8%) from community hospitals. One thousand patients received a cranial CT scan in the ED. Both warfarin and clopidogrel groups had similar demographic and clinical characteristics, although concomitant aspirin use was more prevalent among patients receiving clopidogrel. The prevalence of immediate traumatic intracranial hemorrhage was higher in patients receiving clopidogrel (33/276, 12.0%; 95% confidence interval [CI] 8.4% to 16.4%) than patients receiving warfarin (37/724, 5.1%; 95% CI 3.6% to 7.0%), relative risk 2.31 (95% CI 1.48 to 3.63). Delayed traumatic intracranial hemorrhage was identified in 4 of 687 (0.6%; 95% CI 0.2% to 1.5%) patients receiving warfarin and 0 of 243 (0%; 95% CI 0% to 1.5%) patients receiving clopidogrel.. Although there may be unmeasured confounders that limit intergroup comparison, patients receiving clopidogrel have a significantly higher prevalence of immediate traumatic intracranial hemorrhage compared with patients receiving warfarin. Delayed traumatic intracranial hemorrhage is rare and occurred only in patients receiving warfarin. Discharging patients receiving anticoagulant or antiplatelet medications from the ED after a normal cranial CT scan result is reasonable, but appropriate instructions are required because delayed traumatic intracranial hemorrhage may occur.

Topics: Aged; Aged, 80 and over; Anticoagulants; Clopidogrel; Craniocerebral Trauma; Emergency Service, Hospital; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Risk; Ticlopidine; Time Factors; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Clopidogrel; Craniocerebral Trauma; Female; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Of the 500,000 brain injuries in the United States annually, 80% are considered mild (mild traumatic brain injury). Unfortunately, 2% to 3% of them will subsequently deteriorate and result in severe neurologic dysfunction. Intracerebral changes in the elderly, chronic oral anticoagulation, and platelet inhibition may contribute to the development of intracranial bleeding after minor head injury. We sought to investigate the association of age and the use of anticoagulation and antiplatelet therapy with neurologic deterioration and the need for neurosurgical intervention in patients presenting with mild traumatic brain injury.. A retrospective review of all adult (>14 years) patients admitted to our Level I trauma service with a Glasgow Coma Scale (GCS) score of 14 to 15 who underwent neurosurgical intervention during their hospital stay was performed. Patients were stratified into two groups, age <65 years and age ≥ 65 years. Each group was then further stratified by the use of anticoagulants: warfarin, aspirin, clopidogrel, or a combination. Mechanism of injury, prehospital complaints, admission GCS, type of neurosurgical intervention, intensive care unit length of stay, hospital length of stay, and discharge disposition were evaluated. Z test and logistic regression were used to compare proportions or percentages from different groups.. Of the 7,678 patients evaluated during the study period, 101 (1.3%) required neurosurgical intervention. The ≥ 65 years population underwent significantly more interventions as did those patients on anticoagulants.. All patients aged 65 years or older who present with a GCS score of >13 after head trauma should undergo a screening computed tomography of the head regardless of prehospital use of anticoagulation. Patients younger than 65 years can be selectively screened based on presenting complaints and mechanism of injury provided they are not on anticoagulation.

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Brain Injuries; Clopidogrel; Craniotomy; Decompressive Craniectomy; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Middle Aged; Retrospective Studies; Ticlopidine; Time Factors; Tomography, X-Ray Computed; Warfarin

As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF).. A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993-2008 was conducted within the United Kingdom General Practice Research Database. A nested case-control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year) was calculated by subtracting the ischemic stroke rate (prevented by therapy) from the intracranial hemorrhage (ICH) rate (increased by therapy).. The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73). However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54) and above (-0.49, 95% CI: -1.13, 0.15) therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (-0.07, 95% CI: -0.22, 0.08), though it was seen in certain subgroups.. Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Databases, Factual; Female; General Practice; Humans; Intracranial Hemorrhages; Logistic Models; Male; Odds Ratio; Platelet Aggregation Inhibitors; Preventive Health Services; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; United Kingdom; Warfarin

Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, patients receiving long-term chronic warfarin therapy may face an increased risk for intracranial hemorrhage when treated with tPA. Although current guidelines endorse administering intravenous tPA to warfarin-treated patients if their international normalized ratio (INR) is 1.7 or lower, there are few data on safety of intravenous tPA in warfarin-treated patients in clinical practice.. To determine the risk of symptomatic intracranial hemorrhage (sICH) among patients with ischemic stroke treated with intravenous tPA who were receiving warfarin vs those who were not and to determine this risk as a function of INR.. Observational study, using data from the American Heart Association Get With The Guidelines-Stroke Registry, of 23,437 patients with ischemic stroke and with INR of 1.7 or lower, treated with intravenous tPA in 1203 registry hospitals from April 2009 through June 2011.. Symptomatic intracranial hemorrhage. Secondary end points include life-threatening/serious systemic hemorrhage, any tPA complications, and in-hospital mortality.. Overall, 1802 (7.7%) patients with stroke treated with tPA were receiving warfarin (median INR, 1.20; interquartile range [IQR], 1.07-1.40). Warfarin-treated patients were older, had more comorbid conditions, and had more severe strokes. The unadjusted sICH rate in warfarin-treated patients was higher than in non-warfarin-treated patients (5.7% vs 4.6%, P < .001), but these differences were not significantly different after adjustment for baseline clinical factors (adjusted odds ratio [OR], 1.01 [95% CI, 0.82-1.25]). Similarly, there were no significant differences between warfarin-treated and non-warfarin-treated patients for serious systemic hemorrhage (0.9% vs 0.9%; adjusted OR, 0.78 [95% CI, 0.49-1.24]), any tPA complications (10.6% vs 8.4%; adjusted OR, 1.09 [95% CI, 0.93-1.29]), or in-hospital mortality (11.4% vs 7.9%; adjusted OR, 0.94 [95% CI, 0.79-1.13]). Among warfarin-treated patients with INRs of 1.7 or lower, the degree of anticoagulation was not statistically significantly associated with sICH risk (adjusted OR, 1.10 per 0.1-unit increase in INR [95% CI, 1.00-1.20]; P = .06).. Among patients with ischemic stroke, the use of intravenous tPA among warfarin-treated patients (INR ≤1.7) was not associated with increased sICH risk compared with non-warfarin-treated patients.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Brain Ischemia; Case-Control Studies; Female; Fibrinolytic Agents; Hospital Mortality; Humans; Infusions, Intravenous; International Normalized Ratio; Intracranial Hemorrhages; Male; Registries; Risk; Stroke; Tissue Plasminogen Activator; Warfarin

Topics: Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Intracranial Hemorrhages; Male; Warfarin

Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone.. We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts.. Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003).. Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Factor VIIa; Female; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Male; Recombinant Proteins; Risk Factors; Thromboembolism; Warfarin

Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin.. To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF.. Markov decision model.. The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom.. Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS₂ score ≥1 or equivalent) and no contraindications to anticoagulation.. Lifetime.. Societal.. Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose).. Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios.. The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran.. The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage.. Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up.. In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS₂ score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States.. American Heart Association and Veterans Affairs Health Services Research & Development Service.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Markov Chains; Myocardial Infarction; Quality-Adjusted Life Years; Risk Factors; Sensitivity and Specificity; Stroke; Warfarin

Topics: Anticoagulants; Brain Ischemia; Cerebrovascular Circulation; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Stroke; Thrombolytic Therapy; Warfarin

in controlled trials, anticoagulation with warfarin reduces stroke risk by nearly two thirds, but the benefit has been less pronounced in clinical practice. This report describes the extent of warfarin use, its effectiveness, and its impact on medical costs among Medicare patients with nonvalvular atrial fibrillation.. using claims from >2 million beneficiaries in the Centers for Medicare and Medicaid Services 5% Sample Standard Analytic Files, we identified patients with nonvalvular atrial fibrillation from 2004 to 2005. Warfarin use was inferred from 3 or more tests of the international normalized ratio within 1 year. Incidence of ischemic/hemorrhagic stroke and major bleeding was evaluated. Adjusted risk was calculated by Cox proportional-hazards regression. Medical costs (reimbursed amounts in 2006 US dollars) were estimated by multivariate linear regression.. of patients with nonvalvular atrial fibrillation (N=119 764, mean age=79.3 years), 58.5% were categorized as warfarin users based on the study definition. During an average of 2.1 years' follow-up, the rate of ischemic stroke was 3.9 per 100 patient-years. After multivariate adjustment, ischemic stroke incidence was 27% lower in patients taking warfarin than in patients not taking warfarin (P<0.0001), with no increase in hemorrhagic stroke and a slightly elevated risk of a major bleed. Use of warfarin was independently associated with lower total medical costs, averaging $9836 per patient per year.. these results indicate that 41.5% of Medicare patients with nonvalvular atrial fibrillation are not anticoagulated with warfarin. The incidence of stroke and overall medical costs were significantly lower in patients treated with warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Costs and Cost Analysis; Female; Follow-Up Studies; Humans; Incidence; Insurance Claim Review; Intracranial Hemorrhages; Male; Medicare; Middle Aged; Retrospective Studies; Stroke; United States; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Management; Stroke; Thromboembolism; Warfarin

Stabbing headache can be encountered in both primary and secondary forms, but has been infrequently reported among patients with stroke, and is not known to be associated with a small well-circumscribed brain lesion. A 95-year-old woman taking warfarin presented with the sudden onset of stabbing headache strictly in the right frontal and supraorbital regions, along with gait imbalance and dysarthria. Neuroimaging revealed a small left thalamic hematoma. This association of an acute thalamic lesion with stabbing headache in the contralateral trigeminal distribution is discussed, along with a brief review of stabbing headache occurring in cerebrovascular disease.

Topics: Acute Disease; Aged, 80 and over; Anticoagulants; Female; Headache Disorders, Primary; Hematoma; Humans; Intracranial Hemorrhages; Thalamus; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Contraindications; Drug Administration Schedule; Heart Valve Prosthesis; Humans; Intracranial Hemorrhages; Proportional Hazards Models; Stroke; Time Factors; Warfarin

Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in whom anticoagulation is appropriate. Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing (150 mg bid for patients <80 years, 110 mg bid for patients ≥80 years) versus warfarin and "real-world" prescribing (i.e. warfarin, aspirin, or no treatment in a cohort of warfarin-eligible patients) from a Canadian payer perspective. A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [primary and recurrent ischaemic strokes, systemic embolism, transient ischaemic attack, haemorrhage (intracranial, extracranial, and minor), acute myocardial infarction and death] and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospective study, published literature, and national statistics. Clinical events, summarized as events per 100 patient-years, quality-adjusted life years (QALYs), total costs, and incremental cost effectiveness ratios (ICER) were calculated. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages (0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 "real-world" prescribing) and fewer ischaemic strokes (4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 "real-world" prescribing) per 100 patient-years. The ICER of dabigatran etexilate was $10,440/QALY versus warfarin and $3,962/QALY versus "real-world" prescribing. This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients.

Topics: Aged; Atrial Fibrillation; Benzimidazoles; Canada; Computer Simulation; Cost of Illness; Cost-Benefit Analysis; Dabigatran; Embolism, Air; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Markov Chains; Pyridines; Quality-Adjusted Life Years; Stroke; Warfarin

Patients presenting with ST-segment elevation myocardial infarction (STEMI) frequently use warfarin. Fibrinolytic agents and warfarin both increase bleeding risk, but only a few studies have been published concerning the bleeding risk of warfarin-prescribed patients receiving fibrinolysis. The objective of this study was to define the prevalence for intracranial haemorrhage (ICH) or major bleeding in patients on warfarin treatment receiving pre-hospital fibrinolysis.. This was an observational cohort study. Data for this retrospective case series were collected in Helsinki Emergency Medical Service catchment area from 1.1.1997 to 30.6.2010. All warfarin patients with suspected ST-segment elevation myocardial infarction (STEMI), who received pre-hospital fibrinolysis, were included. Bleeding complications were detected from Medical Records and classified as ICH, major or minor bleeding.. Thirty-six warfarin patients received fibrinolysis during the study period. Fourteen patients had bleeding complications. One (3%, 95% CI 0-15%) patient had ICH, six (17%, 95% CI 7-32%) had major and seven (19%, 95% CI 9-35%) had minor bleeding. The only fatal bleeding occurred in a patient with ICH. Patients' age, fibrinolytic agent used or aspirin use did not predispose to bleeding complications. High International Normalized Ratio (INR) seemed to predispose to bleedings with values over 3, but no statistically significant difference was found.. Bleedings occur frequently in warfarin patients treated with fibrinolysis in the real world setting, but they are rarely fatal.

Topics: Aged; Cohort Studies; Drug Therapy, Combination; Female; Fibrinolysis; Finland; Humans; Intracranial Hemorrhages; Male; Medical Audit; Middle Aged; Myocardial Infarction; Retrospective Studies; Warfarin

Head injury represents one of the most important and frequent traumatic pathology in the emergency department. Among the different risk factors, preinjury use of warfarin has received considerable attention in trauma literature. The aim of this study was to identify further risk indicators of intracranial hemorrhage (ICH) to improve risk stratification of warfarinized patients with minor head injuries.. Medical records of 1,554 adult patients with minor head injuries evaluated by the Emergency Department of Azienda Ospedaliera, Universitaria Careggi from January 2007 to February 2008 were analyzed retrospectively. All the patients included in the study were subjected to blood tests. The international normalized ratio (INR) measured on admission was correlated with the results of head computed tomography scan.. Of the 1,410 patients included in the study, 75 (5.2%) were warfarin anticoagulated at the time of trauma. The INR measured on admission was 2.37 ± 1.04 (mean ± standard deviation), and this value was significantly associated with occurrence of ICH after head trauma (r = 0.37; p < 0.005). For 12 (of 75) patients of this group, the findings of the computed tomography scans were positive. The receiver operating characteristic curve show that the most effective INR cutoff value was 2.43, with a sensitivity of 92%, a specificity of 66%, and positive and negative predictive values of 33% and 97%, respectively.. This study highlights the strong relationship between INR values and the probability of ICH, as shown in previous studies. The high negative predictive value of the identified cutoff, if confirmed, could be used to exclude ICH.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Incidence; Intracranial Hemorrhages; Italy; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Thrombosis; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Intention to Treat Analysis; Intracranial Hemorrhages; Morpholines; Rivaroxaban; Thiophenes; Warfarin

Although generally recommended in atrial fibrillation (AF) patients, the effectiveness and safety of oral anticoagulation in dialysis patients with AF is unknown.. We assembled a cohort of older hemodialysis patients who initiated dialysis without prior record of AF and who had prescription drug benefits through three state-administered programs. The index event was a first hospitalization with diagnosed AF; patients with any recorded prior warfarin use were excluded. Eligible patients survived ≥30 days from discharge, and new warfarin use was recorded from prescription records during that 30-day window. Propensity-matched warfarin users and nonusers were compared using Cox regression. Outcomes included ischemic stroke, hemorrhagic stroke, and mortality.. Among 2313 patients with new AF who survived 30 days from discharge, 249 (10.8%) filled a prescription for warfarin. Comparing 237 warfarin users and 948 propensity-matched nonusers over 2287 person-years of follow-up, the occurrence of ischemic stroke was similar (HR = 0.92; 95% CI, 0.61 to 1.37), whereas warfarin users experienced twice the risk of hemorrhagic stroke (HR = 2.38; 95% CI, 1.15 to 4.96). The risks of stroke, gastrointestinal hemorrhage, and mortality did not differ between groups. As-treated analyses yielded similar findings, as did analyses restricted to patients with CHADS(2) scores ≥2.. Although we confirmed association between warfarin use and hemorrhagic stroke in dialysis patients with AF, we found no association between warfarin use and ischemic stroke. Adequately powered randomized trials are required to conclusively determine the risks and benefits of the studied warfarin indication in hemodialysis patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Drug Prescriptions; Female; Hospitalization; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Logistic Models; Male; Medicare; Middle Aged; Proportional Hazards Models; Renal Dialysis; Risk Assessment; Risk Factors; Stroke; Survival Rate; Time Factors; Treatment Outcome; United States; Warfarin

Warfarin and antiplatelet agents (WAA) are prevalent among trauma patients, but the impact of these agents on patient outcomes has not been clearly defined. In this study, we examined the impact of preinjury WAA on outcomes in trauma patients.. A 40-month (September 2004 to December 2007) retrospective review of data in the trauma registry at a New York State level 1 trauma center was performed. Patients on WAA were compared to those not on these medications. The primary outcome of interest was mortality, and the secondary outcomes of interest were as length of stay (LOS) and disposition on discharge. A separate analysis was done for patients with intracranial hemorrhage (ICH). The chi-square test, the Student t test, and the modified Poisson regression analysis were used to estimate the incident risk ratios for the outcomes.. A total of 3,436 trauma patients were identified, of whom 456 were taking anticoagulants (warfarin, n = 91 patients; aspirin, n = 228; clopidogrel, n = 43; and various combinations, n = 94). Patients on warfarin were 3.1 times more likely to die (relative risk [RR], 3.2; 95% confidence interval [CI], 1.6-6.6), after adjusting for potential confounders. Aspirin and clopidogrel were not associated with increased mortality, but WAA were associated with increased risk of ICH (49.8% vs 30.5%; RR, -1.6; 95% CI, 1.4-1.9). WAA did not affect LOS or disposition. Among patients with ICH, only warfarin increased mortality (28.9% vs 5.8%; RR, -3.1; 95% CI, 1.3-7.2).. Preinjury warfarin treatment was found to be an independent risk factor for mortality. WAA agents increased risk of ICH. Among those patients with ICH, only warfarin was associated with increased mortality. Antiplatelet agents did not affect mortality or LOS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Child; Child, Preschool; Clopidogrel; Cohort Studies; Female; Humans; Infant; Intracranial Hemorrhages; Length of Stay; Male; Middle Aged; Multivariate Analysis; New York; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Risk Factors; Ticlopidine; Trauma Centers; Warfarin; Wounds and Injuries; Young Adult

Patients with prosthetic heart valves require lifelong anticoagulation to prevent thromboembolism. When they have intracranial haemorrhage, anticoagulation has to be withheld. This study was aimed to identify safety duration and complications of anticoagulation withholding in patients with prosthetic heart valves and intracranial haemorrhage. This was a retrospective descriptive study in 26 prosthetic heart valve patients hospitalised in Srinagarind Hospital, Khon Kaen University because of intracranial haemorrhage from 2003 to 2008. Range of anticoagulation withholding was 1 to 26 days with mean 8.5 ± 7.7 days. Most patients (84.6%) were withheld anticoagulation for less than 14 days. There were five in-hospital deaths mostly within 3 days of admission from severe intracranial haemorrhage. No data of reintroduction of anticoagulation was found in three patients because they were lost to follow up. One patient had right basal ganglia infarction after 7 days of anticoagulation withholding. Prosthetic heart valve dysfunction was suspected in one patient who withheld anticoagulant for 76 days. Discontinuation of anticoagulation in patients with prosthetic heart valves and intracranial haemorrhage for less than 7 days was associated with low thromboembolic risk and there was no clinical evidence of prosthetic heart valve dysfunction when anticoagulation was withheld for less than 14 days.

Topics: Adult; Anticoagulants; Aspirin; Atrial Fibrillation; Combined Modality Therapy; Comorbidity; Contraindications; Craniotomy; Female; Heart Valve Prosthesis; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Thailand; Thromboembolism; Time Factors; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Humans; Intracranial Hemorrhages; Pyridines; Risk Factors; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; International Normalized Ratio; Intracranial Hemorrhages; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Treatment Outcome; Warfarin

The use of coagulation factor VIIa (recombinant) for the treatment of warfarin-induced intracranial hemorrhage (ICH) is described.. ICH is a devastating disorder that can be exacerbated by the use of oral anticoagulation. The treatment of warfarin-associated ICH involves the prompt reversal of anticoagulation to allow for surgical procedures, if necessary. Despite limited labeled indications, factor VIIa (recombinant) has been used to reverse warfarin-induced anticoagulation in patients with active hemorrhage, partly due to the rapid effect of factor VIIa on the International Normalized Ratio and the ability to administer the drug quickly in acute settings. The efficacy of factor VIIa (recombinant) for the reversal of anticoagulation in patients with warfarin-associated ICH has been described in several case reports, case series, and retrospective cohort studies. Based on these reports, the use of factor VIIa (recombinant) for the treatment of warfarin-associated ICH may be a viable alternative or adjunct therapy to standard treatment with fresh-frozen plasma and vitamin K. However, due to the nature of these reports, future controlled trials should be conducted to verify the exact place for factor VIIa (recombinant) for this indication. Thromboembolic complications are rare but serious complications secondary to the use of factor VIIa (recombinant). Though differences exist in the reported rate of thromboembolic complications associated with factor VIIa (recombinant), factor VIIa (recombinant) should be used with caution in patients with a predisposition to thromboembolic complications.. Use of factor VIIa (recombinant) may be considered for reversal of anticoagulation in patients with warfarin-associated ICH. However, patients should be screened for increased risk of thrombosis before administration of the drug.

Topics: Anticoagulants; Clinical Trials as Topic; Cohort Studies; Factor VIIa; Humans; Intracranial Hemorrhages; Recombinant Proteins; Retrospective Studies; Thromboembolism; Warfarin

Brain microbleeds are small dot-like lesions appearing as hyposignal on gradient echo T2* MR sequences. They represent microscopic areas of old haemosiderin deposits. They are frequent in the setting of symptomatic cerebrovascular disease and also in older healthy people, suggesting a link with cerebral amyloid angiopathy. Their use as diagnostic or prognostic biomarkers remains uncertain. More recently, they have been highlighted as a potential key factor in the pathogenesis of Alzheimer's disease, connecting the main pathological contributors of amyloid accumulation and cerebrovascular damage. The increasing use of MRI in clinical practice and research has brought brain microbleeds very much to our attention, raising many clinical dilemmas, such as-what do they mean? Should I treat a patient with antithrombotic drugs or thrombolysis? And many others.

Topics: Alzheimer Disease; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Brain; Cerebral Amyloid Angiopathy; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Warfarin

Although parenteral anticoagulants are suitable for short-term indications, oral anticoagulants are preferable for long-term use. Vitamin K antagonists (VKAs) such as warfarin are the only oral anticoagulants currently licensed for long-term use. Although effective, VKAs have multiple limitations that explain, at least in part, their under-use for stroke prevention in patients with atrial fibrillation (AF) and in other indications. Even when they are prescribed, the level of anticoagulation with VKAs is frequently outside the therapeutic range, potentially compromising safety and efficacy. These limitations have prompted development of new oral anticoagulants that target thrombin or Factor Xa. Designed to be given in fixed doses without routine anticoagulation monitoring, these new agents have the potential to revolutionize long-term anticoagulation therapy.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Design; Factor Xa Inhibitors; Humans; International Normalized Ratio; Intracranial Hemorrhages; Stroke; Thrombin; Warfarin

Vestibular schwannomas are benign neoplasms that arise from Schwann cells of the eighth cranial nerve. Most manifest clinically with tinnitus, unilateral sensorineural hearing loss, and dysequilibrium secondary to compression of the vestibulocochlear nerve; major adverse events such as intratumoral hemorrhage causing acute neurologic deterioration are rare. We report the case of a 69-year-old man with a large vestibular schwannoma who required anticoagulation for several medical comorbidities. The patient began having progressively worsening neurologic symptoms, including facial nerve paralysis and dysequilibrium, which confined him to a wheelchair. After presentation, the patient was admitted to the hospital. Several days after alteration of his anticoagulation therapy in preparation for surgery, he developed intracranial hemorrhage. Attempts were made to stabilize the patient, including posterior fossa craniectomy and evacuation of hematoma; however, the intracranial hemorrhage ultimately resulted in a fatal outcome. During this procedure, a biopsy specimen was obtained, showing benign vestibular schwannoma. The literature for intratumoral hemorrhage into vestibular schwannoma and the pathologic findings in our case are reviewed.

Topics: Aged; Anticoagulants; Comorbidity; Disease Progression; Fatal Outcome; Heart Valve Prosthesis; Humans; Immunohistochemistry; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Neuroma, Acoustic; Retrospective Studies; Warfarin

To describe the characteristics, management and outcomes of patients with major trauma who were taking warfarin; explore the use of rapid anticoagulation reversal; and assess the effect of reversal on outcomes.. Retrospective cohort analysis of prospective data extracted from the trauma registries and patient charts of the two adult trauma referral hospitals with neurosurgical units in Western Australia, 2000 to 2005. Inclusion criteria were: major trauma (injury severity score > 15); first international normalised ratio (INR) after injury > 1.4; and documented (in registry or chart) warfarin use.. Eighty patients were identified. Their mean age was 76.8 years. Forty-six were men; 34 were transferred from another hospital; 28 died; and the functional outcomes of 58 were worse at discharge from hospital than before injury. Intracranial haemorrhage (ICH) occurred in 62, of whom 25 died; the difference in mortality between those with ICH and those without ICH was insignificant. Warfarin reversal started 17.4 hours (mean) after injury and the documented period between injury and completion of reversal was 54.2 hours (mean). Multiple logistic regression models, controlling for age, sex, on-scene Glasgow Coma Scale (GCS), initial INR and progressive ICH, showed no independent survival benefit for rapid reversal. Factors associated with mortality were age (22% increase per year [95% CI, 17%-34%]) and progressive ICH on computed tomography scan (24 of the 36 patients with progressive ICH died v one of the 26 patients with stable ICH died). Every point increase in on-scene GCS > 8 increased survival likelihood by 215% (95% CI, 119%-388%).. Patients with major trauma taking warfarin at the time of injury have high mortality rates, poor functional outcomes and long delays to initiation and completion of anticoagulation reversal. Rapid, appropriate warfarin reversal was rarely performed and was not independently associated with survival. Age, low on-scene GCS and progressive ICH were strongly associated with mortality, but presenting INR, ICH v no ICH, and sex were not.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Causality; Cohort Studies; Factor VIII; Female; Fibrinogen; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Plasma; Registries; Treatment Outcome; Vitamin K; Warfarin; Western Australia; Wounds and Injuries

Topics: Accidental Falls; Aged; Anticoagulants; Continuity of Patient Care; Drug Monitoring; Humans; Intracranial Hemorrhages; Male; Malpractice; Medical Records; Warfarin

Warfarin-related intracranial hemorrhage (ICH) is a devastating complication of warfarin therapy. Several studies have demonstrated successful correction of the international normalized ratio (INR) using prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa). To our knowledge, no study has directly compared these agents for treatment of warfarin-related ICH.. We retrospectively reviewed the charts of 15 patients who received rFVIIa and 9 who received PCC for treatment of warfarin-related ICH over a 2-year period. The primary objective was to compare the efficacy of rFVIIa and PCC in correcting the INR to 1.3 or less. Baseline INR was compared to INR obtained within 1, 3, 6, 12, and 24 hours after rFVIIa or PCC administration.. Six patients in the rFVIIa group and five in the PCC group had a follow-up INR within 1 hour of agent administration. In the rFVIIa group, the mean INR decreased from 6.1 to 1.1 and from 2.3 to 1.48 in the PCC group. At 6 hours, all rFVIIa patients and six (67%) PCC patients had at least one subsequent INR, with 93% and 50% correcting to an INR of 1.3 or less. Mean dose for all patients included was 53.4 ± 17.5 μg/kg and 27.8 ± 15.4 units/kg for rFVIIa and PCC, respectively.. Correction of the INR is more reliably obtained with rFVIIa when compared to PCC. Larger, prospective studies comparing these therapies for warfarin-related ICH are needed.

Topics: Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Factor VIIa; Follow-Up Studies; Humans; International Normalized Ratio; Intracranial Hemorrhages; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Warfarin

Topics: Aged; Aged, 80 and over; Aging; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Blood Coagulation; Cytochrome P-450 CYP2C9; Female; Genetic Variation; Humans; Intracranial Hemorrhages; Male; Mixed Function Oxygenases; Risk Factors; Vitamin K Epoxide Reductases; Warfarin

The relationship between antithrombotic therapy and the anatomical location of acute brain hematoma remains disputed. The current study was therefore designed to address this issue.. The medical records and CT images were retrospectively reviewed in 484 consecutive patients with an acute brain hemorrhage (291 men, 193 women; mean age, 67.2+/-12.3 years) who were admitted to the hospital within 7 days of stroke onset from January 1999 through October 2003. Antithrombotic therapy had been performed in 116 patients (AT Group): warfarin (n=38), antiplatelet therapy (n=70), or both (n=8). The other 368 patients had not received antithrombotic therapy (non-AT Group). The hematoma location was compared among the groups.. The location of the hematoma was significantly different between the two groups (p<0.0001). The following locations were seen more frequently in the AT Group than in the non-AT Group: thalamic hemorrhage (44.8% vs. 30.7%), cerebellar hemorrhage (7.8% vs. 2.7%), and lobar hemorrhage (18.1% vs. 11.4%). The clinical characteristics in patients with thalamic, cerebellar, or lobar hemorrhage were compared with those with putaminal hemorrhage. A multivariate analysis using the logistic regression model showed that antithrombotic therapy was an independent factor for cerebellar hemorrhage (OR 3.66, 95%CI 1.31-10.18), lobar hemorrhage (OR 2.27, 95%CI 1.12-4.57), and thalamic hemorrhage (OR 2.20, 95%CI 1.06-4.54) in comparison to putaminal hemorrhage.. It therefore appears that antithrombotic therapy is independently associated with thalamic, cerebellar, and lobar hemorrhage.

Topics: Aged; Brain; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Logistic Models; Male; Multivariate Analysis; Platelet Aggregation Inhibitors; Risk Factors; Tomography, X-Ray Computed; Warfarin

Warfarin-associated fetal hemorrhage is a fatal event. We report the case of a 39-year-old woman who had been taking warfarin for 23 years since undergoing mitral valve replacement. Thereafter, when she was found to be pregnant, the medication was switched to heparin from 6 to 21 weeks of gestation. Following this, she was prescribed oral warfarin again (3.5 mg per day), with a strict control of prothrombin time/international normalized ratio (PT/INR). At 23 weeks of gestation, fetal intracranial hemorrhage occurred because of maternal exposure to warfarin. Maternal PT/INR does not correlate well with the activity of warfarin in the fetus and currently, there is no direct way to prevent fetal intracranial hemorrhage. Hence, further research on the optimal coagulation therapy in pregnant women with valve replacement should be encouraged.

Topics: Adult; Anticoagulants; Female; Fetal Death; Fetal Diseases; Heart Valve Prosthesis Implantation; Heparin; Humans; International Normalized Ratio; Intracranial Hemorrhages; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism; Warfarin

Topics: Anticoagulants; Articulation Disorders; Cerebellar Diseases; Cerebellum; Female; Frontal Lobe; Functional Laterality; Humans; Infarction, Middle Cerebral Artery; Intracranial Hemorrhages; Middle Aged; Neural Pathways; Neuronal Plasticity; Parietal Lobe; Recovery of Function; Remission, Spontaneous; Speech; Verbal Behavior; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Intracranial Hemorrhages; Male; Prospective Studies; Retrospective Studies; Risk Factors; Secondary Prevention; Thromboembolism; Warfarin

Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage.. To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation.. Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003.. An integrated health care delivery system.. 13 559 adults with nonvalvular atrial fibrillation.. Warfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism.. Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used.. Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable.. Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation.. National Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Intracranial Hemorrhages; Male; Prospective Studies; Retrospective Studies; Risk Factors; Secondary Prevention; Thromboembolism; Warfarin

Topics: Drug Interactions; Food-Drug Interactions; Humans; Influenza Vaccines; Intracranial Hemorrhages; Warfarin

Topics: Aged; Anticoagulants; Cerebellar Diseases; Cerebellum; Fatal Outcome; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Warfarin

Conflicting evidence exists surrounding the increased risk of adverse outcome conferred by preinjury anticoagulant and antiplatelet treatment in patients with head injury. The aim of this study was to determine the epidemiology of patients with head injury on anticoagulant and antiplatelet treatment admitted to a hospital from an emergency department (ED).. This was a retrospective analysis of all patients with head injury admitted to a hospital from a major UK ED between 1 January 2005 and 31 December 2007.. 399 patients met the inclusion criteria. 110 patients underwent CT, with 24 having traumatic haemorrhage. Of 271 patients on aspirin, 75 (28%) underwent CT, with 19 of these (25%) having traumatic haemorrhage. Of 89 patients on warfarin, 27 (30%) underwent CT, with 4 of these (15%) having traumatic haemorrhage. Seven of the 24 (29%) patients with traumatic haemorrhage on CT did not undergo urgent ED scanning. All these patients were on aspirin.. This study confirms the need for caution in the early discharge of patients with head injury taking anticoagulant medication. This study also raises concerns that patients taking antiplatelet medication prior to injury may also be at high risk of developing covert serious intracranial haemorrhage and suggests the need for a well-designed cohort study looking at antiplatelet risk in head injury.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Craniocerebral Trauma; Emergency Service, Hospital; Female; Hospitalization; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Retrospective Studies; Tomography, X-Ray Computed; Warfarin

Randomized trials and observational studies support using an international normalized ratio (INR) target of 2.0 to 3.0 for preventing ischemic stroke in atrial fibrillation. We assessed whether the INR target should be adjusted based on selected patient characteristics.. We conducted a case-control study nested within the ATRIA cohort's 9217 atrial fibrillation patients taking warfarin to define the relationship between INR level and the odds of thromboembolism (TE; mainly stroke) and of intracranial hemorrhage (ICH) relative to INR 2.0 to 2.5. We identified 396 TE cases and 164 ICH cases during follow-up. Each case was compared with 4 randomly selected controls matched on calendar date and stroke risk factors using matched univariable analyses and conditional logistic regression. We explored modification of the INR-outcome relationships by the following stroke risk factors: prior stroke, age, and CHADS(2) risk score. Overall, the odds of TE were low and stable above INR 1.8. Compared with INR 2.0 to 2.5, the relative odds of TE increased strikingly at INR <1.8 (eg, odds ratio, 3.72; 95% CI, 2.67 to 5.19, at INR 1.4 to 1.7). The odds of ICH increased markedly at INR values >3.5 (eg, odds ratio, 3.56; 95% CI: 1.70 to 7.46, at INR 3.6 to 4.5). The relative odds of ICH were consistently low at INR <3.6. There was no evidence of lower ICH risk at INR levels <2.0. These patterns of risk did not differ substantially by history of stroke, age, or CHADS(2) risk score.. Our results confirm that the current standard of INR 2.0 to 3.0 for atrial fibrillation falls in the optimal INR range. Our findings do not support adjustment of INR targets according to previously defined stroke risk factors.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Databases, Factual; Female; Follow-Up Studies; Humans; Intracranial Hemorrhages; Logistic Models; Male; Risk Factors; Stroke; Thromboembolism; Warfarin

To examine the efficacy of recombinant factor VIIa (rVIIa) in reversing warfarin-induced coagulopathy in trauma patients presenting with intracranial hemorrhage (ICH).. Retrospective, cohort-controlled database review.. Level 1, university-affiliated trauma center.. 54 patients presenting with ICH associated with chronic warfarin therapy, 30 of whom were treated with rVIIa, and the other 24 patients treated conventionally.. We examined initial and subsequent coagulation studies (prothrombin time, international normalized ratio [INR]), blood product requirement, and clinical outcome, including time to reverse anticoagulation, duration of reversal, and subsequent mortality.. Patients treated with rVIIa required significantly less plasma (4 vs 7 units) to correct their INR, and corrected in a much shorter period of time (2.4 vs 10 hrs). The duration of corrected INR after rVIIa was dose-dependent.. Factor rVIIa provides prompt correction of the INR of dose-dependent duration in patients with ICH intracranial hemorrhage associated with warfarin use.

Topics: Aged; Anticoagulants; Blood Coagulation; Cohort Studies; Dose-Response Relationship, Drug; Factor VIIa; Female; Humans; Intracranial Hemorrhages; Male; Recombinant Proteins; Retrospective Studies; Time Factors; Warfarin

Nonrheumatic atrial fibrillation (AF) is a common cause of embolic stroke. Warfarin therapy can reduce stroke risk by two-thirds in patients with AF, but therapy may not always be used or always be used optimally.. This study sought to document the patterns of anticoagulant use and the determinants and incidence of stroke, intracranial hemorrhage, and arterial thromboembolism in US patients with AF.. Using health insurance claims and laboratory results, we examined events per unit of person-time and used Poisson regression to quantify the association of AF outcomes with the international normalized ratio (INR) and other covariates.. In 116,969 patients age > or =40 years with an insurance claim for AF or atrial flutter between 1999 and 2005, warfarin was prescribed to 45%, and 48% had no claim for any anticoagulant or antiplatelet agent. Subtherapeutic INR levels (<2.0) raised the incidence of stroke (relative risk [RR]: 2.39, 95% confidence interval [CI]: 1.68 to 3.41) and arterial thromboembolism (RR: 5.68, 95% CI: 1.88 to 17.10) compared with therapeutic INR levels, whereas supratherapeutic INR levels (>3.0) doubled the incidence of intracranial hemorrhage (RR: 2.11, 95% CI: 1.16 to 3.84). Further covariate adjustment had little effect on these estimates.. Warfarin remains underused within the outpatient setting. Nontherapeutic INR levels are associated with increased risk of stroke, bleeding, and thromboembolism compared with therapeutic INR levels.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Stroke; Thromboembolism; Treatment Outcome; United States; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Bias; Humans; Intracranial Hemorrhages; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Cerebrum; Cesarean Section; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Intracranial Hemorrhages; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Ultrasonography, Prenatal; Warfarin

With the recent increase in the use of antithrombotic therapy, intracerebral hemorrhage (ICH) has been found to be a common complication. We determined whether the use of oral antithrombotic therapy and the patients' preexisting comorbidities were predictive of cerebellar hemorrhage (CH; previously reported to be associated with anticoagulants) as compared to other ICH, and whether antithrombotic therapy affected the clinical severity of CH.. A study of 327 consecutive patients hospitalized in our institute within 3 days after the onset of ICH, including 38 patients with a CH.. CH accounted for 12% of all ICH, 75% of which occurred in patients on warfarin therapy with an international normalized ratio (INR) for prothrombin time >2.5 (p < 0.0001), and 33% of which occurred in patients on ticlopidine therapy (p = 0.017). Warfarin therapy with an INR >2.5 and high blood glucose on admission were independently predictive of CH as compared to other ICH. In addition, previous ischemic stroke (p = 0.002) and heart diseases (p = 0.018) were more prevalent in patients with CH than in those with other ICH. The number of major arteriosclerotic comorbidities and risk factors was also independently predictive of CH risk.. We confirmed that warfarin therapy with an INR >2.5 is associated with CH. Patients with CH frequently had arteriosclerotic comorbidities requiring antithrombotic therapy that can complicate their acute management.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Arteriosclerosis; Aspirin; Blood Glucose; Cerebellar Diseases; Female; Fibrinolytic Agents; Heart Diseases; Humans; Intracranial Hemorrhages; Japan; Male; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stroke; Ticlopidine; Time Factors; Warfarin

During anticoagulation for prevention of stroke in patients with non-valvular atrial fibrillation (NVAF), bleeding is the most serious complication. In Western countries, the incidences of major bleeding and intracranial hemorrhages with low-dose warfarin are known to occur at a rate of 0.4-1.3% and 0.2% per year, respectively. The purpose of this study was to investigate the incidence and risk factors for major bleeding related with warfarin therapy in Japanese patients with NVAF.. From August 2004 to July 2005, 667 NVAF patients treated with warfarin for NVAF were followed-up. The target prothrombin time-international normalized ratio (PT-INR) value was set at 1.6-2.6 (low-dose warfarin). The exposure on warfarin was 503 patient-years (average PT-INR 2.00 +/-0.40). During the follow-up period, 12 major bleeding complications occurred (2.38% per patient-year), which included 3 intracranial hemorrhages (0.60% per patient-year). Among the patients' characteristics, average PT-INR > or =2.27 during the study was identified as an independent risk factor for major bleeding.. The incidence of major bleeding and intracranial hemorrhages in Japanese NVAF patients with low-dose warfarin therapy was 2.38% and 0.60% per patient-year, respectively, which is higher than in Westerners.

Topics: Age Distribution; Aged; Anticoagulants; Asian People; Atrial Fibrillation; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Prothrombin Time; Risk Factors; Sex Distribution; Warfarin

The risk of intracerebral hemorrhage (ICH) in patients receiving antithrombotic therapy is well known. However, there is sparse literature regarding the risk of intracerebral hemorrhage in patients receiving warfarin, who have an intracranial meningioma.. We report a case of a 66-year-old man who developed multifocal ICHs in the context of supratherapeutic anticoagulation. There was sparing of the intracranial meningioma despite the development and growth of multiple intraparenchymal hemorrhages that resulted in death. We also review the literature evaluating the risk of ICH in anticoagulated patients with an intracranial meningioma.. The findings of this case lend further support to the gradually developing notion of relative safety of anticoagulation in patients with meningioma. They also underscore the importance of close monitoring of the INR.

Topics: Aged; Anticoagulants; Brain Neoplasms; Diagnosis, Differential; Fatal Outcome; Humans; Intracranial Hemorrhages; Male; Meningioma; Tomography, X-Ray Computed; Warfarin

This study was designed to study racial/ethnic differences in the risk for intracranial hemorrhage (ICH) and the effect of warfarin on ICH risk among patients with atrial fibrillation (AF).. Nonwhites are at greater risk for ICH than whites in the general population. Whether this applies to patients with AF and whether warfarin therapy is associated with comparable risk of ICH in nonwhites are unknown.. We retrospectively identified a multiethnic stroke-free cohort hospitalized with nonrheumatic AF. Warfarin use and anticoagulation intensity were assessed by searching pharmacy and laboratory records. Crude ICH event rates were calculated by Poisson regression. Cox proportional hazard models were constructed to assess the independent effect of race/ethnicity on ICH after adjusting for age, gender, hypertension, diabetes, heart failure, and warfarin exposure.. Between 1995 and 2000, we identified 18,867 qualifying AF hospitalizations (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian) and 173 qualifying ICH events over 3.3 years follow-up. Achieved anticoagulation intensity was lower among blacks but not different between the other groups. Warfarin was associated with increased ICH risk in all races, but the magnitude of risk was greater among nonwhites. There were no gender differences. The hazard ratio for ICH with whites as referent was 4.06 for Asians (95% confidence interval [CI] 2.47 to 6.65), 2.06 for Hispanics (95% CI 1.31 to 3.24), and 2.04 (95% CI 1.25 to 3.35) for blacks.. Nonwhites with AF were at greater risk for warfarin-related ICH. Blacks, Hispanics, and Asians were at successively greater ICH risk than whites.

Topics: Age Distribution; Aged; Aged, 80 and over; Asian People; Atrial Fibrillation; Black People; California; Cohort Studies; Comorbidity; Ethnicity; Female; Follow-Up Studies; Hispanic or Latino; Humans; Hypertension; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Prevalence; Racial Groups; Retrospective Studies; Risk Factors; Sex Distribution; Stroke; Warfarin; White People

Limited information exists regarding thrombolysis among anticoagulated acute stroke patients. We present data from three consecutive patients, on active warfarin therapy, treated with intra-arterial reteplase.. All patients were screened for the presence of intracranial hemorrhage. Warfarin was reversed with fresh frozen plasma in all patients and cerebral angiography and intra-arterial administration of reteplase was performed. Computed tomographic scans were performed to detect any subsequent intracranial hemorrhage. Ages ranged from 58 to 79 years with initial National Institutes of Health Stroke Scale scores ranging from 12 to 17. Baseline international normalized ratios (INRs) were 1.99-2.25. None of the patients suffered from intracranial hemorrhage following thrombolysis, and two of the patients experienced early neurological improvement.. Low dose, intra-arterial reteplase following acute reversal of elevated INR is feasible and may offer a potential treatment for patients suffering with acute ischemic stroke while receiving active warfarin treatment.

Topics: Acute Disease; Aged; Anticoagulants; Brain Ischemia; Cerebral Angiography; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Injections, Intra-Arterial; Intracranial Hemorrhages; Male; Middle Aged; Recombinant Proteins; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Warfarin

The relationship between preinjury warfarin use and outcomes after traumatic brain injury in elderly trauma patients remains controversial. We hypothesized that, among elderly warfarin users, the degree of anticoagulation, rather than warfarin therapy itself, would predict the severity of traumatic brain injury.. Retrospective study (2004-2006) of all elderly trauma patients (age >/=65 years) who were evaluated by the trauma service at a Level I trauma center and underwent computed tomography of the head for suspicion of an intracranial injury was performed. Three cohorts were grouped: (1) warfarin users with an admission International Normalized Ratio >/=2 (therapeutic group), (2) warfarin users with an admission International Normalized Ratio <2 (nontherapeutic group), and (3) warfarin nonusers. Main outcome variables were presenting with a Glasgow Coma Scale (GCS) score

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Brain Injuries; Chi-Square Distribution; Female; Glasgow Coma Scale; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Predictive Value of Tests; Retrospective Studies; Statistics, Nonparametric; Tomography, X-Ray Computed; Warfarin

The authors report two cases of spontaneous intracranial haemorrhage after elective craniotomy for resection of cerebral tumour. Both patients had mechanical aortic valve prostheses and were on regular warfarin therapy. In both cases, warfarin therapy was discontinued 5 days prior to surgery and unfractionated heparin administered intravenously until 12 h before surgery. Both patients were re-anticoagulated with subcutaneous low molecular weight heparin within the first week postcraniotomy-both developed life-threatening intracranial haemorrhage requiring urgent evacuation. The authors emphasize the risk of re-anticoagulation without postoperative imaging and the disadvantages of therapeutic dose, low molecular weight heparin in the postoperative period.

Topics: Anticoagulants; Aortic Valve; Brain Neoplasms; Craniotomy; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Intracranial Hemorrhages; Male; Middle Aged; Postoperative Hemorrhage; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

A large population of patients on oral anticoagulants is exposed to the risk of traumatic brain injury (TBI). Effects of age and anticoagulation on TBI outcomes need to be assessed separately.. Retrospective analysis of consecutive series of TBI patients (age 18 years and older) in a suburban teaching hospital.. A total of 1,493 adult blunt head trauma patients between January 2001 and May 2005 were analyzed. Of these, 159 patients were warfarin-anticoagulated at the time of trauma. The mortality in anticoagulated patients was statistically significantly higher than in the control group (38/159, 23.9% vs. 66/1,334, 4.9%; p < 0.001; odds ratio 6.0). Mortality of patients over 70 years of age was significantly higher than in the younger population (p < 0.001). Both mortality and the occurrence of intracranial hemorrhage (ICH) after head trauma were significantly increased with higher INR (Cochran's linear trend p < 0.001), especially with INR over 4.0 (mortality 50%, risk of ICH 75%). Preinjury warfarin anticoagulation and age were found to be predictive of survival in a binary logistic regression model (92.5% correct prediction, p = 0.027). Addition of Injury Severity Score and initial Glasgow Coma Score to this model only modestly improved its predictive performance (95.4% correct prediction, p < 0.001).. Both age and warfarin anticoagulation are independent predictors of mortality after blunt TBI. Warfarin anticoagulation carries a six-fold increase in TBI mortality. Age over 70 years and excessive anticoagulation are associated with higher mortality, as well.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Craniocerebral Trauma; Humans; Intracranial Hemorrhages; Middle Aged; Regression Analysis; Retrospective Studies; Risk Factors; United States; Warfarin; Wounds, Nonpenetrating

To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation, whether or not they are taking warfarin therapy.. Cohort study.. Integrated healthcare delivery system. Thirteen thousand five hundred fifty-nine adults with nonvalvular atrial fibrillation.. Patient data were collected from automated clinical and administrative databases using previously validated search algorithms. Medical charts were reviewed from patients hospitalized were for major hemorrhage (intracranial, fatal, requiring >or=2 units of transfused blood, or involving a critical anatomic site). Age was categorized into four categories (<60, 60-69, 70-79, and >or=80), and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age, stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage.. A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy. Hemorrhage rates rose with older age, with an average increase in hemorrhage rate of 1.2 (95% confidence interval (CI) 1.0-1.4) per older age category in patients taking warfarin and 1.5 (95% CI=1.3-1.8) in those not taking warfarin. Intracranial hemorrhage rates were significantly higher in those aged 80 and older (adjusted rate ratio=1.8, 95% CI=1.1-3.1 for those taking warfarin, adjusted rate ratio=4.7, 95% CI=2.4-9.2 for those not taking warfarin) than in those younger than 80.. Older age increases the risk of major hemorrhage, particularly intracranial hemorrhage, in patients with atrial fibrillation, whether or not they are taking warfarin. Hemorrhage rates were generally comparable with those reported in previous randomized trials, indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; California; Female; Follow-Up Studies; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Survival Rate; Warfarin

Preinjury warfarin anticoagulation has been shown to increase the mortality of traumatic intracranial hemorrhage. We have evaluated the impact on patient mortality of the rapid triage of patients at risk for warfarin associated traumatic intracranial hemorrhage.. A "Coumadin Protocol" was implemented in January, 2001 in the Emergency Department that expedited triage of anticoagulated trauma patients to immediate physician evaluation. Patient outcomes during a 2 year period were compared with a matched control group of similarly injured, anticoagulated patients who were treated before protocol initiation.. Thirty-five patients were treated after implementation of the Coumadin Protocol. Mean time until warfarin reversal was 4.3 +/- 4.4 hours, and there was a 37% mortality. Twenty-two control patients had a mean time to reversal of 4.2 +/- 2.9 hours, with a 45% mortality (p = 0.610). Ten protocol patients were shown to have intracranial hemorrhage progression by computed tomography (CT) scan, with a 60% mortality rate. Seventeen patients had follow-up CT scan and showed no progression; only one of these patients (6%) died (p = 0.004). Hemorrhage severity based on the initial CT scan did not predict mortality or hemorrhagic progression.. We conclude from these data that a trauma center protocol for rapid identification of intracranial bleeding without a concomitant therapeutic protocol does not improve survival in head injured patients on preinjury warfarin.

Topics: Aged; Anticoagulants; Disease Progression; Female; Humans; Intracranial Hemorrhages; Male; Retrospective Studies; Risk; Tomography, X-Ray Computed; Triage; Warfarin; Wounds and Injuries

Cerebral venous thrombosis (CVT) is an uncommon but serious type of stroke. Thrombosis may involve the cortical or deep veins or the venous sinuses. The presenting clinical features are non-specific. We report a 48-year-old man with CVT who presented with fever, bitemporal throbbing headache, and generalised convulsion. Computed tomography (CT) of the brain revealed acute haemorrhages over right anterior frontal and posterior temporal regions with surrounding oedema and right anterior temporal subcortical oedema. The initial diagnosis was herpes simplex encephalitis. Absence of venous flow over the right transverse and sigmoid sinuses during the venous phase of digital subtraction angiography (DSA) revealed CVT. He was anti-coagulated for 6 months. An underlying cause of CVT was not detected. A high index of suspicion is required when risk factors of CVT are present. CT brain may be normal or showing non-specific findings. Magnetic resonance imaging plus venography, CT venography, or DSA is diagnostic.

Topics: Angiography, Digital Subtraction; Anticoagulants; Brain; Diagnosis, Differential; Encephalitis, Herpes Simplex; Fever; Frontal Lobe; Heparin, Low-Molecular-Weight; Humans; Intracranial Hemorrhages; Intracranial Thrombosis; Male; Middle Aged; Seizures; Temporal Lobe; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Humans; International Normalized Ratio; Intracranial Hemorrhages; Warfarin

Patients at high risk for falls are presumed to be at increased risk for intracranial hemorrhage, and high risk for falls is cited as a contraindication to antithrombotic therapy. Data substantiating this concern are lacking.. Quality improvement organizations identified 1245 Medicare beneficiaries who were documented in the medical record to be at high risk of falls and 18261 other patients with atrial fibrillation. The patients were elderly (mean 80 years), and 48% were prescribed warfarin at hospital discharge. The primary endpoint was subsequent hospitalization for an intracranial hemorrhage, based on ICD-9 codes.. Rates (95% confidence interval [CI]) of intracranial hemorrhage per 100 patient-years were 2.8 (1.9-4.1) in patients at high risk for falls and 1.1 (1.0-1.3) in other patients. Rates (95% CI) of traumatic intracranial hemorrhage were 2.0 (1.3-3.1) in patients at high risk for falls and 0.34 (0.27-0.45) in other patients. Hazard ratios (95% CI) of other independent risk factors for intracranial hemorrhage were 1.4 (1.0-3.1) for neuropsychiatric disease, 2.1 (1.6-2.7) for prior stroke, and 1.9 (1.4-2.4) for prior major bleeding. Warfarin prescription was associated with intracranial hemorrhage mortality but not with intracranial hemorrhage occurrence. Ischemic stroke rates per 100 patient-years were 13.7 in patients at high risk for falls and 6.9 in other patients. Warfarin prescription in patients prone to fall who had atrial fibrillation and multiple additional stroke risk factors appeared to protect against a composite endpoint of stroke, intracranial hemorrhage, myocardial infarction, and death.. Patients at high risk for falls with atrial fibrillation are at substantially increased risk of intracranial hemorrhage, especially traumatic intracranial hemorrhage. However, because of their high stroke rate, they appear to benefit from anticoagulant therapy if they have multiple stroke risk factors.

Topics: Accidental Falls; Aged; Anticoagulants; Atrial Fibrillation; Contraindications; Female; Humans; Incidence; Intracranial Hemorrhages; Male; Risk Factors; Stroke; Warfarin

Warfarin-associated intracranial hemorrhage (ICH) requires rapid normalization of clotting function. Current therapies are associated with significant complications and/or prolonged time to correction of coagulopathy. Recombinant factor VIIa (FVIIa) might allow faster and safer correction of coagulopathy.. This article presents a retrospective chart review of all patients with warfarin-associated ICH treated in a neurology/neurosurgery intensive care unit over an 11-month period.. All patients were treated to rapidly reverse the warfarin effect. Fifteen patients received vitamin K and fresh frozen plasma (FFP) alone (FFP group). Twelve patients also received FVIIa (FVIIa group). The median times from presentation to an international normalization ratio (INR) of less than 1.3 were 32.2 and 8.8 hours in the FFP the FVIIa groups, respectively (p = 0.016). INR normalized slowly (at 110 and 130 hours, respectively) in two patients with end-stage renal failure who were given FVIIa, one of whom developed disseminated intravascular coagulation after three doses of FVIIa. No other complications occurred from FVIIa administration. One patient in the FFP group developed severe pulmonary edema.. FVIIa may be an effective adjunct to FFP in warfarin-related ICH, facilitating faster correction of INR and decreasing FFP requirements. A prospective, randomized trial is needed to confirm these preliminary findings and to determine whether there is a clinical benefit.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Drug Therapy, Combination; Factor VII; Factor VIIa; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Plasma; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Vitamin K; Warfarin

Our goal was to establish whether psychosocial risk factors for nonadherence, previously identified as negative predictors of warfarin prescribing, are predictors of adverse events for patients with nonvalvular atrial fibrillation receiving warfarin.. Retrospective cohort analysis.. Ohio Medicaid administrative database.. We studied Ohio Medicaid recipients with nonvalvular atrial fibrillation receiving warfarin to determine whether a history of substance abuse, psychiatric illness, or social factors (identified as conditions perceived to be barriers to adherence) are predictors of adverse events, including stroke, intracranial hemorrhage, and gastrointestinal bleeding. Multivariable risk ratios were calculated for each risk factor using Cox proportional hazards models.. 9,345 patients were identified as having nonvalvular atrial fibrillation and receiving 2 or more warfarin prescriptions between 1997 and 2002. The event rates for the sample as a whole were 1.5 strokes, 0.7 intracranial hemorrhages, and 4.3 gastrointestinal bleeds per 100 person-years of follow-up. Subjects with substance abuse had the highest adjusted risk ratio, 2.4 (95% confidence interval [CI]: 1.4, 4.0) for an intracranial hemorrhage while receiving warfarin, followed by subjects with psychiatric illness, adjusted risk ratio of 1.5 (95% CI: 1.04, 2.1). Subjects with psychiatric illness also had an adjusted risk ratio of 1.4 (95% CI: 1.1, 1.7) for stroke. Patients in all 3 identified risk groups were at a significantly increased risk of gastrointestinal bleeding.. Patients with nonvalvular atrial fibrillation treated with warfarin who have psychosocial risk factors for nonadherence have an increased risk of adverse events.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Mental Disorders; Middle Aged; Retrospective Studies; Risk Factors; Socioeconomic Factors; Stroke; Substance-Related Disorders; Treatment Outcome; Treatment Refusal; Warfarin

The annual incidence of warfarin-related bleeding at Brigham and Women's Hospital increased from 0.97/1,000 patient admissions in the first time period (January 1995 to October 1998) to 1.19/1,000 patient admissions in the second time period (November 1998 to August 2002) of this study. The proportion of patients with major and intracranial bleeding increased from 20.2% and 1.9%, respectively, in the first time period, to 33.3% and 7.8%, respectively, in the second.

Topics: Adult; Age Distribution; Aged; Anticoagulants; Cohort Studies; Female; Hemorrhage; Hospitalization; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Probability; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; Survival Rate; Thromboembolism; Time Factors; Warfarin

The Framingham Heart Study records of participants with atrial fibrillation (AF) during 1980 and 1994 were retrospectively reviewed to determine the prevalence of warfarin and aspirin use in AF. Anticoagulant use increased significantly in the 393 men and women (mean ages 72.5 and 79.0 years, respectively) who developed AF over the observation period: aspirin use increased from 14% to 39% in men and from 19% to 33% in women, and warfarin use increased from 10% to 39% in men and from 17% to 38% in women. There were no significant gender differences in anticoagulant use (p = 0.61), but participants using warfarin were younger. A total of 65 participants (17%) had major bleeding complications

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Heart Failure; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prevalence; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Risk Factors; Warfarin

The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity.. To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage.. Case-control study.. Academic medical center.. 170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation.. The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use.. Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 [95% CI, 1.3 to 4.7]; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 [CI, 2.3 to 9.4]; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 [CI, 0.8 to 2.2]).. Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder.. The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Case-Control Studies; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Multivariate Analysis; Odds Ratio; Risk Factors; Warfarin

Topics: Blood Coagulation Disorders; Drug-Related Side Effects and Adverse Reactions; Hematuria; Humans; Intracranial Hemorrhages; Male; Middle Aged; Rodenticides; Warfarin

To assess the effects of recombinant factor VIIa (rFVIIa) on hemorrhage volume and functional outcomes in warfarin-related acute intracranial hemorrhage (ICH), which has a 30-day mortality of more than 50%.. We reviewed the clinical, laboratory, and radiographic features of a consecutive series of 7 patients (median age, 87 years; 5 women) with symptomatic, nontraumatic warfarin-related acute ICH treated with intravenous rFVIIa at St. Luke's Hospital in Jacksonville, Fla, between December 2002 and September 2003. Prestroke baseline functional status was assessed with the modified Rankin Scale. Outcome was assessed with the Glasgow Outcome Scale.. The international normalized ratio decreased from a mean of 2.7 before administration of rFVIIa to 1.08 after administration of rFVIIa. The median prestroke score on the modified Rankin Scale was zero. The median presenting score on the Glasgow Coma Scale was 14 (range, 4-15). The mean time from onset to treatment was 6.2 hours. The mean initial dose of rFVIIa was 62.1 microg/kg. One patient underwent placement of an external ventricular drain, and another underwent craniotomy and hematoma evacuation. Five of the 7 patients survived and were dismissed from the hospital with severe disability (Glasgow Outcome Scale, 3); 2 patients died during hospitalization.. Intravenous bolus administration of rFVIIa can rapidly lower the international normalized ratio and appears to be safe for patients with warfarin-related ICH. Prospective controlled studies are needed to determine whether rFVIIa can prevent hematoma expansion and improve neurologic outcomes in patients with warfarin-related ICH.

Topics: Acute Disease; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Drug Administration Schedule; Factor VII; Factor VIIa; Female; Follow-Up Studies; Glasgow Coma Scale; Humans; Infusions, Intravenous; International Normalized Ratio; Intracranial Hemorrhages; Male; Recombinant Proteins; Retrospective Studies; Risk Assessment; Sampling Studies; Severity of Illness Index; Survival Rate; Treatment Outcome; Warfarin

The frequency of use of warfarin anticoagulation increases significantly in the elderly population. It remains controversial whether this puts these patients at increased risk for hemorrhagic complications after trauma.. We prospectively evaluated consecutive trauma patients who were taking warfarin and compared their outcomes to a group of age-matched patients with head injuries but not taking warfarin.. One hundred fifty-nine trauma patients on warfarin were evaluated, 94 (59%) with some type of head trauma; 25 of these 94 patients (27%) had documented intracranial trauma. Fifteen patients died (9.4%); they had an international normalized ratio of 3.3 +/- 1.6 versus 3.0 +/- 2.1 for survivors in the warfarin group (p = 0.585). Twelve deaths were in the group of 25 patients with intracranial injuries (48%). Three patients without head injury died (5%) of other causes not related to warfarin or hemorrhage at a mean of 13 days after admission. Ten of 12 patients on warfarin with intracranial injuries who died had documented loss of consciousness (LOC); two patients who died secondary to an isolated intracranial injury had no LOC. Of 70 age-matched patients with head trauma not taking warfarin, 47 (67%) had intracranial injury and 5 of these died (10%) (p < 0.001 for both values compared with study patients). There were no significant differences for patients with intracranial injury comparing those on warfarin and those who were not in terms of age, gender, mechanism of injury, Injury Severity Score, or Glasgow Come Scale score.. We conclude that the preinjury use of warfarin does not place the trauma patient at increased risk for fatal hemorrhagic complications in the absence of head trauma. Furthermore, the presence of a head trauma alone is not predictive of mortality. However, the presence of intracranial injury is strongly associated with a mortality rate that is significantly higher than patients with head trauma who are not taking warfarin. LOC is also associated with mortality, but the absence of loss of consciousness does not reliably indicate the absence of intracranial injury or risk of death.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Prospective Studies; Warfarin

The incidence of stroke in patients with atrial fibrillation is greatly reduced by oral anticoagulation, with the full effect seen at international normalized ratio (INR) values of 2.0 or greater. The effect of the intensity of oral anticoagulation on the severity of atrial fibrillation-related stroke is not known but is central to the choice of the target INR.. We studied incident ischemic strokes in a cohort of 13,559 patients with nonvalvular atrial fibrillation. Strokes were identified through hospitalization data bases and validated on the basis of medical records, which also provided information on the use of warfarin or aspirin, the INR at admission, and coexisting illnesses. The severity of stroke was graded according to a modified Rankin scale. Thirty-day mortality was ascertained from hospitalization and mortality files.. Of 596 ischemic strokes, 32 percent occurred during warfarin therapy, 27 percent during aspirin therapy, and 42 percent during neither type of therapy. Among patients who were taking warfarin, an INR of less than 2.0 at admission, as compared with an INR of 2.0 or greater, independently increased the odds of a severe stroke in a proportional-odds logistic-regression model (odds ratio, 1.9; 95 percent confidence interval, 1.1 to 3.4) across three severity categories and the risk of death within 30 days (hazard ratio, 3.4; 95 percent confidence interval, 1.1 to 10.1). An INR of 1.5 to 1.9 at admission was associated with a mortality rate similar to that for an INR of less than 1.5 (18 percent and 15 percent, respectively). The 30-day mortality rate among patients who were taking aspirin at the time of the stroke was similar to that among patients who were taking warfarin and who had an INR of less than 2.0.. Among patients with nonvalvular atrial fibrillation, anticoagulation that results in an INR of 2.0 or greater reduces not only the frequency of ischemic stroke but also its severity and the risk of death from stroke. Our findings provide further evidence against the use of lower INR target levels in patients with atrial fibrillation.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Female; Fibrinolytic Agents; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Severity of Illness Index; Stroke; Warfarin

A 27-yr-old woman who had been taking warfarin for 10 yr after mitral valve replacement became pregnant. After knowing her pregnancy, she received heparinization for nine weeks instead of warfarin, and took oral anticoagulant again. At 24 weeks of gestation, fetal ultrasound and MRI showed a left subdural hematoma, and the pregnancy was terminated. Subdural hematoma was demonstrated on autopsy. Fatal bleeding of the fetus is a rare complication of maternal warfarin medication, occurring mostly in the second or third trimester. There is no alternative regimen available, so that regular monitoring by fetal ultrasound and strict control of warfarin dose with regular measurement of prothrombin time are the best way to prevent intrauterine fetal death due to bleeding.

Topics: Adult; Anticoagulants; Ductus Arteriosus, Patent; Female; Fetal Diseases; Heart Valve Diseases; Hematoma; Heparin; Humans; Intracranial Hemorrhages; Maternal Exposure; Pregnancy; Pregnancy Complications, Hematologic; Prothrombin Time; Warfarin

Topics: Administration, Oral; Anticoagulants; Drug Administration Schedule; Hemorrhage; Humans; Intracranial Hemorrhages; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Intracranial Hemorrhages; Stroke; Warfarin

Anticoagulant (AC) and antiplatelet (AP) drugs are effectively used in the prevention of thromboembolic events, with the trade-off of bleeding side effects, particularly intracranial. The aim of this study was to determine the incidence of intracranial bleeding in the population of Reggio Emilia and to investigate the potential effect of AC and AP drugs.. We reviewed all the patients admitted for cerebral hemorrhages to our hospital between April 1998 and September 2000. Data were collected with a standardized form. All the patients were followed-up to estimate long-term mortality. Chi(2) and t-tests were used as appropriate. Logistic regression analysis was performed to test predictors of mortality. Pharmaceutical department data were employed to estimate the total number of patients receiving AC and AP drugs.. We found 241 cases (107/134 female/male, mean age 61 years, 133/107 spontaneous/traumatic events, 0.32/1,000/year overall). Twenty-nine and 47 of these patients were being given AC or AP drugs, respectively (4.9/1,000/year and 3.7/1,000/year). The relative risk of intracranial bleeding was 11.5 in AP and 15.3 in AC treated patients. Two patients (one underwent neurosurgery and one thrombolytic treatment) were excluded from mortality and risk factors analysis. Six patients were lost from follow-up and excluded from mortality analysis. Overall mortality was 100/233 (42.9%); mortality in traumatic events was 25/103 (24.2%) versus 75/130 (57.7%) in spontaneous events. Mortality was 19/29 (65.5%), 26/47 (55.3%) and 55/157 (35%) in AC recipients, AP recipients, and untreated patients, respectively. This increased risk was mainly confined to traumatic events (p = 0.06), without difference between AC and AP recipients. At the time of the event, the mean duration of oral AC treatment was 26.3 months (range 1-120). Mean INR was = 3.1 (range 1.6-8.8). Mortality was significantly predicted by the Glasgow Coma Scale Score (GCS) at admission (p < 0.0001), by the type of bleeding (spontaneous versus traumatic) (p = 0.0026), and by age (p < 0.0001).. Careful selection of patients and prevention of traumatic events are the main candidate mechanisms to reduce intracranial bleeding in patients being treated with AC and AP drugs.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Female; Humans; Incidence; Infant; Intracranial Hemorrhages; Italy; Male; Middle Aged; Mortality; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

To better understand the tradeoffs between the efficacy of anticoagulation with warfarin and its side effects in the oldest old with nonrheumatic atrial fibrillation (AF).. Cost-effectiveness analysis.. Published literature, including meta-analyses when available, and web-based sources.. Those aged 65 to 100 with AF.. Anticoagulation with warfarin.. Quality-adjusted life expectancy and cost.. Anticoagulation is not effective in persons with AF who do not have other risk factors, even in the oldest old. The best argument for its use (prolongation of life at an acceptable cost) can be made in those at major risk for stroke because of previous stroke or transient ischemic attack, diabetes mellitus, and hypertension, but poor quality of life before anticoagulation and comorbidities that carry their own risks of dying diminish benefits. The decision to anticoagulate the oldest old with AF must take into consideration the risk of hemorrhagic stroke and of death from hemorrhagic stroke that existed before anticoagulation, the increased risk of hemorrhagic stroke and of death from hemorrhagic stroke while anticoagulated, and the efficacy of anticoagulation. Cost-effectiveness is also influenced by the cost of warfarin, the risk of major extracranial bleeding, the risk (natural and anticoagulated) of death from hemorrhagic stroke, the rate of ischemic stroke, the cost of major extracranial bleeding and hemorrhagic strokes, the cost of nursing home care, and the fraction of patients with stroke who need nursing home care.. There is no compelling evidence to date that anticoagulation prolongs quality-adjusted life expectancy in the oldest old with nonrheumatic AF. More studies that better estimate the risk of intracranial bleeding with and without anticoagulation in the oldest old are needed before recommendations can be made. The oldest old who are most likely to benefit are those who have a high risk of stroke secondary to risk factors other than age alone, although quality of life and life expectancy related to these risk factors limit obtained benefit. Recommendations that all older persons with AF should be anticoagulated are premature.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Contraindications; Cost-Benefit Analysis; Female; Humans; Intracranial Hemorrhages; Male; Quality-Adjusted Life Years; Risk Factors; Stroke; Warfarin

We studied intracranial damage in patients with mild head injuries who were taking warfarin. Of the 215,785 individuals who visited the Mount Auburn and Beth Israel accident and emergency departments during our study, we identified records for 144 patients by anticoagulation status and computed tomography (CT) imaging. We retrospectively reviewed these patients and ten (7%, 95% CI 3-11) with clinically important injuries on cranial CT. Our findings suggest that patients with head injuries who receive anticoagulants have a similar or greater risk of intracranlal injury to those falling into a previously defined moderate-risk category, invalidating a previous conclusion that CT scanning is unnecessary in such patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Female; Humans; Intracranial Hemorrhages; Male; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Warfarin

Topics: Aged; Anticoagulants; Craniocerebral Trauma; Emergency Medical Services; Humans; Intracranial Hemorrhages; Male; Tomography, X-Ray Computed; Warfarin

Warfarin is the most common oral anticoagulant used for chronic anticoagulation therapy. Even without any antecedent trauma overanticoagulation can result in intracranial hemorrhage. The triad of anticoagulation with warfarin, age greater than 65 years, and traumatic head injury frequently produces a lethal brain hemorrhage. A retrospective review of more than 2000 patients admitted to the Trauma Service between September 1998 and May 2000 produced 278 patients with head injury and CT-documented intracranial hemorrhage. Of these patients 21 were admitted with an elevated prothrombin time (PT) due to anticoagulation with warfarin. Eighteen patients (86%) were above the age of 70. The most common indications for anticoagulation were atrial fibrillation (71%), deep venous thrombosis (19%), aortic valve replacement (9%), and ischemic cerebral infarcts (9%). Fourteen injuries were the result of a fall, one resulted from a gunshot wound, and one resulted from an assault. The remaining five patients were excluded as their history, workup, and evaluation by neurosurgery suggested a spontaneous bleed leading to fall rather than a fall causing a traumatic bleed. The average Glasgow Coma Score on admission was 11. The average PT and International Normalized Ratio (INR) on admission were 19.2 and 2.99 respectively. Eight of the 16 patients analyzed died. The risk of intracranial hemorrhage with relatively minor head injury is increased dramatically in the anticoagulated patient. A mortality rate of 50 per cent far exceeds the mortality rate in patients with similar head injuries who are not anticoagulated. In addition the risk/benefit equation of anticoagulation for the elderly is more complex and differs from that for younger patients. Perhaps more frequent and judicious monitoring of prothrombin time levels with lower therapeutic ranges (INR 1.5-2) is necessary.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Craniocerebral Trauma; Female; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Male; Retrospective Studies; Venous Thrombosis; Warfarin

The recommended treatment of ischaemic stroke patients with atrial fibrillation (AF) is anticoagulation therapy with warfarin sodium and if this is contraindicated then aspirin should be used. The management of patients on warfarin therapy can be complicated and there is a risk of intra-cranial haemorrhage in elderly patients. However, these are the patients who stand to gain the most benefit from this treatment and therefore increased use of warfarin for secondary prophylaxis is likely to lead to a lower rate of subsequent admissions and less morbidity. The recommended treatment for these patients has often not been fully instigated in practice. This study was carried out in order to determine whether a group of patients admitted to a teaching hospital with diagnosis of ischaemic stroke and atrial fibrillation received appropriate antithrombotic therapy. Details of patients admitted with acute stroke during 1997 were obtained from the Dundee Stroke Database and information was extracted from the relevant clinical notes. Twenty-five out of 42 patients (60%) were considered eligible for anticoagulation and 14 out of those 25 (56%) were found to be on warfarin either on admission or subsequently. Of patients aged less than 75 years, 8/10 (80%) were on warfarin, whereas only 6/15 (40%) of those aged 75 years and older were being anticoagulated.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Contraindications; Female; Hospitalization; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Factors; Scotland; Stroke; Warfarin

Topics: Cerebral Angiography; Cerebral Hemorrhage; Hematoma; Hematoma, Subdural; Humans; Intracranial Hemorrhages; Neurosurgery; Neurosurgical Procedures; Toxicology; Warfarin