warfarin and Cardiovascular-Diseases

Pharmacogenetics (PGx) is the relationship between an individual's genetic variations and the response to pharmacological treatment. We chose to perform an overview of reviews on PGx testing-guided treatment for cardiovascular diseases, based on clinically relevant gene-drug pairs. We conducted a search on Medline, Embase and Cochrane Library, from their inception to 18 June 2020. The most studied gene-drug pairs were clopidogrel and warfarin associated with cytochrome p450 and vitamin K epoxide reductase complex subunit 1 genes (

Topics: Anticoagulants; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C9; Genotype; Humans; Pharmacogenetics; Review Literature as Topic; Vitamin K Epoxide Reductases; Warfarin

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Fibrinolytic Agents; Hemostatics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazoles; Lipids; Organosilicon Compounds; Warfarin

To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care.. We conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted.. We screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin-CYP2C9/VKORC1 or clopidogrel-CYP2C19. A payer's perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies.. We found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel-CYP2C19 and warfarin-CYP2C9/VKORC1, but evidence is limited in other drug-gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.

Topics: Cardiovascular Diseases; Clopidogrel; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Vitamin K Epoxide Reductases; Warfarin

There is a special interest in the implementation of pharmacogenetics in clinical practice, although there are some barriers that are preventing this integration. A large part of these pharmacogenetic tests are focused on drugs used in oncology and psychiatry fields and for antiviral drugs. However, the scientific evidence is also high for other drugs used in other medical areas, for example, in cardiology. In this article, we discuss the evidence and guidelines currently available on pharmacogenetics for clopidogrel, warfarin, acenocoumarol, and simvastatin and its implementation in daily clinical practice.

Topics: Acenocoumarol; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C9; Guidelines as Topic; Humans; Pharmacogenetics; Precision Medicine; Simvastatin; Warfarin

Various antithrombotic agents are clinically used to inhibit the cascade of arterial or venous thrombosis in cardiovascular diseases. Dual antiplatelet therapy with aspirin and P2Y

Topics: Anticoagulants; Area Under Curve; Aspirin; Blood Platelets; Cardiovascular Diseases; Catheter Ablation; Coronary Artery Disease; Fibrinolytic Agents; Hemorrhage; Hemostasis; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Thrombosis; Warfarin

The goal of this study was to compare the relative efficacy and safety of different types of interventions for stroke prevention in patients with cardiovascular and cerebrovascular diseases.. This network meta-analysis (NMA) was conducted with a random effects model of Bayesian framework using Stata version 12.0. Odds ratios (ORs) and their credible intervals (CrIs) were applied for the efficacy and safety evaluation of various medical interventions, including aspirin, dipyridamole, ticlopidine, warfarin, and apixaban. In addition, the ranking of probability of every clinical outcome was estimated by comparing the surface under the cumulative ranking curve.. Compared with dabigatran, both edoxaban and aspirin + warfarin exhibited a higher rate of all-cause stroke (OR, 2.84 [95% CrI, 1.17-6.97]; OR, 3.42 [95% CrI, 1.20-9.84]). With respect to intracranial hemorrhage, aspirin + clopidogrel yielded worse outcomes than 7 treatments, including placebo, apixaban, aspirin, aspirin + dipyridamole, cilostazol, clopidogrel, and dabigatran (OR, 2.21 [95% CrI, 1.45-3.40]; OR, 2.11 [95% CrI, 1.05-4.17]; OR, 1.53 [95% CrI, 1.11-2.15]; OR, 1.78 [95% CrI, 1.01-3.03]; OR, 4.17 [95% CrI, 1.37-14.28]; OR, 1.85 [95% CrI, 1.22-2.86]; and OR, 2.56 [95% CrI, 1.37-4.76]). In terms of ischemic stroke, dabigatran provided better efficacy than placebo, aspirin, and aspirin + dipyridamole (OR, 0.36 [95% CrI, 0.18-0.72]; OR, 0.43 [95% CrI, 0.21-0.84]; and OR, 0.41 [95% CrI, 0.17-0.94]). As for mortality, dabigatran resulted in a lower mortality compared with aspirin, aspirin + clopidogrel, edoxaban, and warfarin (OR, 0.48 [95% CrI, 0.23-0.97]; OR, 0.40 [95% CrI, 0.17-0.92]; OR, 0.27 [95% CrI, 0.10-0.72]; and OR, 0.52 [95% CrI, 0.28-0.92]).. There are still some limitations to our NMA research. For instance, the lack of direct evidence for some therapies resulted in inconsistencies, particularly for warfarin compared with placebo and clopidogrel under different end points. Moreover, the included randomized controlled trials for patients with cardiovascular and cerebrovascular diseases are relatively broad, involving atrial fibrillation, myocardial infarction, and large-artery atherosclerosis stroke. Although further research is needed, dabigatran is highly recommended based on the present NAM for the treatment of cardiovascular and cerebrovascular diseases due to the drug's efficacy and safety.

Topics: Anticoagulants; Aspirin; Bayes Theorem; Cardiovascular Diseases; Clopidogrel; Dabigatran; Dipyridamole; Hemorrhage; Humans; Odds Ratio; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Thiazoles; Ticlopidine; Treatment Outcome; Warfarin

Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high-throughput genetics and genomics technology and newer genome-wide study approaches, a number of genetic variations across the human genome were uncovered. Evidence suggests that genetic defects could influence CVD development and inter-individual responses to widely used cardiovascular drugs like clopidogrel, aspirin, warfarin, and statins, and therefore, they may be integrated into clinical practice. If clinically validated, better understanding of these genetic variations may provide new opportunities for personalized diagnostic, pharmacogenetic-based drug selection and best treatment in personalized medicine. However, numerous gaps remain unsolved due to the lack of underlying pathological mechanisms for how genetic predisposition could contribute to CVD. This review provides an overview of the extraordinary scientific progress in our understanding of genetic and genomic basis of CVD as well as the development of relevant genetic biomarkers for this disease. Some of the actual limitations to the promise of these markers and their translation for the benefit of patients will be discussed.

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Genetic Predisposition to Disease; Genetic Variation; Genome, Human; Genomics; Humans; Pharmacogenetics; Precision Medicine; Ticlopidine; Warfarin

Patients with atrial fibrillation have an increased risk for stroke, systemic embolism and cardiovascular events, including myocardial infarction and cardiovascular death. However, the majority of studies that have analyzed the efficacy of anticoagulants have been focused only on their effects on the risk of stroke. Areas covered: The available evidence about the association between atrial fibrillation and cardiovascular disease as well as the effects of oral anticoagulation on cardiovascular death and myocardial infarction, with a particular focus on direct oral anticoagulants, was updated in this review. Expert opinion: The management of patients with atrial fibrillation should not be limited to the prevention of stroke, but should also include the prevention of cardiovascular events. Despite treatment with vitamin K antagonists, many patients with atrial fibrillation still develop cardiovascular complications, particularly individuals whose anticoagulation is difficult to control. Direct oral anticoagulants overcome the majority of limitations of vitamin K antagonists and compared with warfarin, they lead to a greater reduction in the risk of stroke or systemic embolism, all-cause mortality, and intracranial hemorrhage. Although these drugs can only be compared indirectly, it seems that not all direct oral anticoagulants are equal with regard to the prevention of myocardial infarction.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Embolism; Humans; Myocardial Infarction; Stroke; Warfarin

There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I

Topics: Algorithms; Anticoagulants; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Predictive Value of Tests; Warfarin

To conduct a systematic review and meta-analysis of complication rates and outcomes in patients undergoing endovascular procedures who receive uninterrupted versus interrupted warfarin therapy.. Literature published between 1990 and 2014 was searched for reports of comparative studies of vascular procedures. Information on periprocedural complications and patient deaths less than 30 days after the procedure was extracted. A random effects model was used and odds ratios (ORs) were reported. An OR of less than 1 was considered to indicate lower risk of the outcome with uninterrupted warfarin therapy. Meta-analysis was conducted by using meta-analysis software.. A total of 27 studies of 20,376 patients were included. For arterial procedures, there were no significant differences between the uninterrupted and interrupted warfarin therapy groups in access site hematoma (OR, 0.59; 95% confidence interval [CI]: 0.33, 1.03; P = .06), any bleeding complications (OR, 0.56; 95% CI: 0.30, 1.06; P = .07), mortality (OR, 1.40; 95% CI: 0.37, 5.25; P = .62), intracranial hemorrhage (OR, 0.55; 95% CI: 0.03, 8.91; P = .68), ischemic stroke (OR, 0.85; 95% CI: 0.12, 5.84; P = .87), and major bleeding (OR, 0.56; 95% CI: 0.21, 1.51; P = .25). For venous procedures, uninterrupted warfarin was associated with lower odds of access site hematoma (OR, 0.70; 95% CI: 0.50, 0.99; P = .04), any bleeding complications (OR, 0.61; 95% CI: 0.48, 0.77; P < .01), ischemic stroke (OR, 0.21; 95% CI: 0.10, 0.45; P < .01), and major bleeding (OR, 0.64; 95% CI: 0.51, 0.80; P < .01). For arterial and venous procedures combined, uninterrupted warfarin was associated with lower odds of access site hematoma (OR, 0.68; 95% CI: 0.51, 0.91; P = .01), bleeding complications (OR, 0.59; 95% CI: 0.48, 0.74; P < .01), ischemic stroke (OR, 0.25; 95% CI: 0.12, 0.50; P < .01), and major bleeding (OR, 0.61; 95% CI: 0.49, 0.77; P < .01). Heterogeneity in most analyses was low, and confidence in the estimates was moderate.. Uninterrupted perioperative warfarin therapy is safe for patients undergoing arterial procedures, but interrupted warfarin may be preferred for those undergoing venous procedures; no differences in outcome rates were found in the randomized controlled trials. Future studies should be performed to validate these results.

Topics: Anticoagulants; Cardiovascular Diseases; Endovascular Procedures; Humans; 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

The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs.. We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione.. Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs.. In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Cardiovascular Diseases; Diarrhea; Fibrinolytic Agents; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Obesity; Phenindione; Phenprocoumon; Vitamin K; Warfarin

CKD is an independent risk factor for cardiovascular disease (CVD). Thus, patients with CKD often require treatment with cardiovascular drugs, such as antiplatelet, antihypertensive, anticoagulant, and lipid-lowering agents. There is significant interpatient variability in response to cardiovascular therapies, which contributes to risk for treatment failure or adverse drug effects. Pharmacogenomics offers the potential to optimize cardiovascular pharmacotherapy and improve outcomes in patients with CVD, although data in patients with concomitant CKD are limited. The drugs with the most pharmacogenomic evidence are warfarin, clopidogrel, and statins. There are also accumulating data for genetic contributions to β-blocker response. Guidelines are now available to assist with applying pharmacogenetic test results to optimize warfarin dosing, selection of antiplatelet therapy after percutaneous coronary intervention, and prediction of risk for statin-induced myopathy. Clinical data, such as age, body size, and kidney function have long been used to optimize drug prescribing. An increasing number of institutions are also implementing genetic testing to be considered in the context of important clinical factors to further personalize drug therapy for patients with CVD.

Topics: Adrenergic beta-Antagonists; Anticoagulants; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 Enzyme System; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Pharmacogenetics; Phenotype; Platelet Aggregation Inhibitors; Precision Medicine; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Solute Carrier Proteins; Ticlopidine; Vitamin K Epoxide Reductases; 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

Antithrombotic drug therapy is a main cornerstone - sometimes a fairly uneven cornerstone - of today's clinical practice. Patients treated with antithrombotic drugs appear sometimes unawaited at those of our colleagues, who are not necessarily experts of this narrow field. Furthermore, new and newer molecules of antiplatelet and anticoagulant medicines have come into practice, frequently in combination. This dramatic development has been important to patients; pharmacological - and recently nonpharmacological - antithrombotic treatment has paved the way to improve current modalities in cardiology. Combining elements of the "old four" (heparin, coumadin, aspirin, clopidogrel) have been the basis of any improvement for a long time. Nowadays, there has been an involvement of new drugs, direct oral anticoagulants into practice. It is time now to catch up in using new anticoagulants, regardless of our current speciality in medicine. Orv. Hetil., 2016, 157(38), 1507-1510.

Topics: Administration, Oral; Anticoagulants; Aspirin; Cardiology; Cardiovascular Diseases; Clopidogrel; Fibrinolytic Agents; Heparin; Humans; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

The role of thrombin in vascular physiology and pathophysiology continues to impact our understanding of many cellular processes and systems including the function of platelets, endothelial cells, smooth muscle cells, leukocytes and the regulation of the coagulation cascade. Recent acute coronary syndrome clinical trial results that have compared the use of parenteral or oral anticoagulants versus or in combination with anti-platelet agents have forced a reexamination of the importance of thrombin activity in influencing patient outcomes, particularly in the area of secondary prevention. The debate of the need to include oral anticoagulation as a concomitant or replacement therapy to an antiplatelet regimen as a means to improve patient outcomes requires further examination and larger prospective clinical trials.

Topics: Acute Coronary Syndrome; Administration, Oral; Animals; Anticoagulants; Atherosclerosis; Blood Coagulation; Blood Platelets; Cardiovascular Diseases; Clinical Trials as Topic; Fibrinolytic Agents; Humans; Inflammation; Mice; Platelet Aggregation Inhibitors; Receptor, PAR-1; Receptors, Thrombin; Risk Factors; Secondary Prevention; Thrombin; Warfarin

Consensus practice guidelines and the implementation of clinical therapeutic advances are usually based on the results of large, randomized clinical trials (RCTs). However, RCTs generally inform us on an average treatment effect for a presumably homogeneous population, but therapeutic interventions rarely benefit the entire population targeted. Indeed, multiple RCTs have demonstrated that interindividual variability exists both in drug response and in the development of adverse effects. The field of pharmacogenomics promises to deliver the right drug to the right patient. Substantial progress has been made in this field, with advances in technology, statistical and computational methods, and the use of cell and animal model systems. However, clinical implementation of pharmacogenetic principles has been difficult because RCTs demonstrating benefit are lacking. For patients, the potential benefits of performing such trials include the individualization of therapy to maximize efficacy and minimize adverse effects. These trials would also enable investigators to reduce sample size and hence contain costs for trial sponsors. Multiple ethical, legal, and practical issues need to be considered for the conduct of genotype-based RCTs. Whether pre-emptive genotyping embedded in electronic health records will preclude the need for performing genotype-based RCTs remains to be seen.

Topics: Adrenergic beta-Antagonists; Anticoagulants; Biomarkers; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Forecasting; Genetic Markers; Genomics; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Sequence Analysis, DNA; Ticlopidine; Warfarin

Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear.. To estimate the mortality outcomes in patients treated with DOACs vs. warfarin (or another vitamin K antagonist).. MEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference abstracts and www.clinicaltrials.gov, were searched, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs with warfarin in patients with non-valvular atrial fibrillation or venous thromboembolism.. Thirteen randomized controlled trials involving 102 707 adult patients were included in the analysis. The case-fatality rate of major bleeding was 7.57% (95% CI, 6.53-8.68; I(2) = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16-13.07; I(2) = 33.3%) in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient-years (95% CI, 0.12-0.20; I(2) = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43-0.64; I(2) = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82-0.94; I(2) = 0%) and all-cause mortality (RR, 0.91; 95% CI, 0.87-0.96; I(2) = 0%).. The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case-fatality rate of major bleeding, cardiovascular mortality and all-cause mortality.

Topics: Adult; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Hemorrhage; Humans; Mortality; Risk; Thromboembolism; Thrombophilia; Treatment Outcome; Vitamin K; Warfarin

One-third of women with heart disease use medication for the treatment of cardiovascular disease (CVD) during pregnancy. Increased plasma volume, renal clearance, and liver enzyme activity in pregnant women change the pharmacokinetics of these drugs, often resulting in the need for an increased dose. Fetal well-being is a major concern among pregnant women. Fortunately, many drugs used to treat CVD can be used safely during pregnancy, with the exception of high-dose warfarin in the first trimester, angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, amiodarone, and spironolactone. A timely and thorough discussion between the cardiologist and the pregnant patient about the potential benefits and adverse effects of medication for CVD is important. Noncompliance with necessary treatment for cardiovascular disorders endangers not only the mother, but also the fetus. This Review is an overview of the pharmacokinetic changes in medications for CVD during pregnancy and the safety of these drugs for the fetus. The implications for maternal treatment are discussed. The Review also includes a short section on the cardiovascular effects of medication used for obstetric indications.

Topics: Amiodarone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Spironolactone; Warfarin

Interindividual heterogeneity in drug response is a central feature of all drug therapies. Studies in individual patients, families, and populations over the past several decades have identified variants in genes encoding drug elimination or drug target pathways that in some cases contribute substantially to variable efficacy and toxicity. Important associations of pharmacogenomics in cardiovascular medicine include clopidogrel and risk for in-stent thrombosis, steady-state warfarin dose, myotoxicity with simvastatin, and certain drug-induced arrhythmias. This review describes methods used to accumulate and validate these findings and points to approaches--now being put in place at some centers--to implementing them in clinical care.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Antithrombins; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Organic Anion Transporters; Pharmacogenetics; Polymorphism, Single Nucleotide; Precision Medicine; Ticlopidine; Vitamin K Epoxide Reductases; Warfarin

Cardiovascular disease is a leading cause of morbidity and mortality worldwide. Pharmacogenomics is the study of genetic determinants of interindividual variation in drug response and aims to facilitate personalized medicine, through genotype-informed drug and dose selection, to maximize drug efficacy and/or minimize adverse drug reactions. Despite high expectations, no cardiovascular pharmacogenomic association is currently in widespread clinical practice; evidential, logistical, financial, and knowledge implementation barriers exist. Nevertheless, VKORC1, CYP2C9, and CYP4F2 variants have been associated with warfarin dose requirements, and CYP2C19 variants have been associated with perturbed antiplatelet response to clopidogrel. However, at present, controversy exists over the clinical utility of these genetic associations. There is an increased risk of simvastatin-induced muscle toxicity in SLCO1B1*5 carriers, ADRB1 and ADRA2C polymorphisms are associated with differential response to bucindolol, and rare congenital arrhythmia gene variants have been identified in drug-induced torsade de pointes. Practical benefits are still anticipated, but much work remains.

Topics: Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Anticoagulants; Cardiovascular Diseases; Clopidogrel; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Platelet Aggregation Inhibitors; Renin-Angiotensin System; Ticlopidine; Warfarin

Published data on the association between vitamin K epoxide reductase complex 1 (VKORC1)-1639G > A polymorphism and warfarin dose requirement are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed.. Studies were identified in English-language articles by search of PubMed and Embase database (inception to July 2013). A total of 32 prospective clinical trials involving 5005 patients were identified and included for analysis. Overall, the weighted mean maintenance dosage of warfarin in patients with the -1639AA genotype decreased 2.62 mg/d compared with that in the -1639GG genotype patients (95% CI -3.10 to -2.14; P < 0.00001) when 24 eligible studies were pooled into the meta-analysis. Furthermore, significantly lower warfarin dose requirement was found in patients with GA genotype versus GG genotype (WMD, -1.32; 95% CI -1.67 to -0.96; P < 0.00001). In the subgroup analysis by ethnicity, statistically significant lower maintenance dosage of warfarin in patients with the AA genotype versus GG genotype were found in both Caucasians (WMD, -2.47; 95% CI -2.92 to -2.03; P < 0.00001) and Asians (WMD, -2.84; 95% CI -4.57 to -1.11; P = 0.001).. This meta-analysis indicated that the VKORC1-1639G > A genetic polymorphism is associated with the variation of interindividual warfarin dose requirement in different ethnic populations.

Topics: Anticoagulants; Asian People; Atrial Fibrillation; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Embolism; Genetic Markers; Genotype; Humans; Polymorphism, Single Nucleotide; Stroke; Thrombosis; Vitamin K Epoxide Reductases; Warfarin; White People

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Choice Behavior; Humans; Warfarin

Topics: Adenosine; Aspirin; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Clopidogrel; Dabigatran; Drug Interactions; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine; Warfarin

In the coming years, genomics will impact clinical practice in multiple ways. However, one of the most important applications will be in the determination of the best treatments in personalized medicine. This is, in fact, one of the fields in which genetic variants have already been most successful and useful to clinicians. Here, we briefly review the current state of the art on pharmacogenomics and its applications to modern cardiovascular medicine.

Topics: Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Platelet Aggregation Inhibitors; Precision Medicine; Warfarin

Cardiovascular disease is a leading cause of death worldwide. Many pharmacologic therapies are available that aim to reduce the risk of cardiovascular disease but there is significant inter-individual variation in drug response, including both efficacy and toxicity. Pharmacogenetics aims to personalize medication choice and dosage to ensure that maximum clinical benefit is achieved whilst side effects are minimized. Over the past decade, our knowledge of pharmacogenetics in cardiovascular therapies has increased significantly. The anticoagulant warfarin represents the most advanced application of pharmacogenetics in cardiovascular medicine. Prospective randomized clinical trials are currently underway utilizing dosing algorithms that incorporate genetic polymorphisms in cytochrome P450 (CYP)2C9 and vitamin k epoxide reductase (VKORC1) to determine warfarin dosages. Polymorphisms in CYP2C9 and VKORC1 account for approximately 40 % of the variance in warfarin dose. There is currently significant controversy with regards to pharmacogenetic testing in anti-platelet therapy. Inhibition of platelet aggregation by aspirin in vitro has been associated with polymorphisms in the cyclo-oxygenase (COX)-1 gene. However, COX-1 polymorphisms did not affect clinical outcomes in patients prescribed aspirin therapy. Similarly, CYP2C19 polymorphisms have been associated with clopidogrel resistance in vitro, and have shown an association with stent thrombosis, but not with other cardiovascular outcomes in a consistent manner. Response to statins has been associated with polymorphisms in the cholesterol ester transfer protein (CETP), apolipoprotein E (APOE), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, calmin (CLMN) and apolipoprotein-CI (APOC1) genes. Although these genes contribute to the variation in lipid levels during statin therapy, their effects on cardiovascular outcomes requires further investigation. Polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene is associated with increased statin exposure and simvastatin-induced myopathy. Angiotensin-converting enzyme (ACE) inhibitors and β-adrenoceptor antagonists (β-blockers) are medications that are important in the management of hypertension and heart failure. Insertion and deletion polymorphisms in the ACE gene are associated with elevated and reduced serum levels of ACE, respectively. No significant association was reported between the polymorphism and blood pressure reduction

Topics: Animals; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cardiovascular Agents; Cardiovascular Diseases; Cytochrome P-450 CYP2C9; Disease Management; Humans; Pharmacogenetics; Warfarin

The past decade has seen tremendous advances in our understanding of the genetic factors influencing response to a variety of drugs, including those targeted at treatment of cardiovascular diseases. In the case of clopidogrel, warfarin, and statins, the literature has become sufficiently strong that guidelines are now available describing the use of genetic information to guide treatment with these therapies, and some health centers are using this information in the care of their patients. There are many challenges in moving from research data to translation to practice; we discuss some of these barriers and the approaches some health systems are taking to overcome them. The body of literature that has led to the clinical implementation of CYP2C19 genotyping for clopidogrel, VKORC1, CYP2C9; and CYP4F2 for warfarin; and SLCO1B1 for statins is comprehensively described. We also provide clarity for other genes that have been extensively studied relative to these drugs, but for which the data are conflicting. Finally, we comment briefly on pharmacogenetics of other cardiovascular drugs and highlight β-blockers as the drug class with strong data that has not yet seen clinical implementation. It is anticipated that genetic information will increasingly be available on patients, and it is important to identify those examples where the evidence is sufficiently robust and predictive to use genetic information to guide clinical decisions. The review herein provides several examples of the accumulation of evidence and eventual clinical translation in cardiovascular pharmacogenetics.

Topics: Animals; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Biotransformation; Cardiovascular Agents; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Mixed Function Oxygenases; Organic Anion Transporters; Patient Selection; Pharmacogenetics; Phenotype; Platelet Aggregation Inhibitors; Precision Medicine; Risk Assessment; Risk Factors; Ticlopidine; Vitamin K Epoxide Reductases; Warfarin

Variability in drug responsiveness is a sine qua non of modern therapeutics, and the contribution of genomic variation is increasingly recognized. Investigating the genomic basis for variable responses to cardiovascular therapies has been a model for pharmacogenomics in general and has established critical pathways and specific loci modulating therapeutic responses to commonly used drugs such as clopidogrel, warfarin, and statins. In addition, genomic approaches have defined mechanisms and genetic variants underlying important toxicities with these and other drugs. These findings have not only resulted in changes to the product labels but also have led to development of initial clinical guidelines that consider how to facilitate incorporating genetic information to the bedside. This review summarizes the state of knowledge in cardiovascular pharmacogenomics and considers how variants described to date might be deployed in clinical decision making.

Topics: Adrenergic beta-Antagonists; Cardiovascular Agents; Cardiovascular Diseases; Clopidogrel; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Polymorphism, Genetic; Practice Guidelines as Topic; Ticlopidine; Warfarin

The primary objective was to assess the cost-effectiveness of new oral anticoagulants compared with warfarin in patients with nonvalvular atrial fibrillation. Secondary objectives related to assessing the cost-effectiveness of new oral anticoagulants stratified by center-specific time in therapeutic range, age, and CHADS2 score.. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained. Analysis used a Markov cohort model that followed patients from initiation of pharmacotherapy to death. Transition probabilities were obtained from a concurrent network meta-analysis. Utility values and costs were obtained from published data. Numerous deterministic sensitivity analyses and probabilistic analysis were conducted.. The incremental cost per QALY gained for dabigatran 150 mg versus warfarin was $20,797. Apixaban produced equal QALYs at a higher cost. Dabigatran 110 mg and rivaroxaban were dominated by dabigatran 150 mg and apixaban. Results were sensitive to the drug costs of apixaban, the time horizon adopted, and the consequences from major and minor bleeds with dabigatran. Results varied by a center's average time in therapeutic range, a patient's CHADS2 score, and patient age, with either dabigatran 150 mg or apixaban being optimal.. Results were highly sensitive to patient characteristics. Rivaroxaban and dabigatran 110 mg were unlikely to be cost-effective. For different characteristics, apixaban or dabigatran 150 mg were optimal. Thus, the choice between these two options may come down to the price of apixaban and further evidence on the impact of major and minor bleeds with dabigatran.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Cost-Benefit Analysis; Dabigatran; Drug Costs; Hemorrhage; Humans; Markov Chains; Middle Aged; Morpholines; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Time Factors; Warfarin

In the past decade, significant strides have been made in the area of cardiovascular pharmacogenomic research, with the discovery of associations between certain genotypes and drug-response phenotypes. While the motivations for personalized and predictive medicine are promising for patient care and support a model of health system efficiency, the implementation of pharmacogenomics for cardiovascular therapeutics on a population scale faces substantial challenges. The greatest obstacle to clinical implementation of cardiovascular pharmacogenetics may be the lack of both reproducibility and agreement about the validity and utility of the findings. In this review, we present the scientific evidence in the literature for diagnostic variants for the US FDA-labeled cardiovascular therapies, namely CYP2C19 and clopidogrel, CYP2C9/VKORC1 and warfarin, and CYP2D6/ADRB1 and β-blockers. We also discuss the effect of HMGCR/LDLR in decreasing the effectiveness of low-density lipoprotein cholesterol with statin therapy, the SLCO1B1 genotype and simvastatin myotoxicity, and ADRB1/ADD1 for antihypertensive response.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Biomarkers, Pharmacological; Cardiovascular Diseases; Clopidogrel; Dose-Response Relationship, Drug; Genotype; Humans; Polymorphism, Genetic; Ticlopidine; Warfarin

Warfarin is the most widely used oral anticoagulant and has been available for more than 65 years. The last decade has brought a host of new orally available anticoagulants with promising features to clinical trials and some have already been approved for limited indications. As patients are starting to be switched to these new agents there is a need to gain understanding of the subsets of patients that will benefit the most from the new alternatives and whether warfarin is still the best choice for some subpopulations. With this knowledge we will provide the individual patient with the drug that has the best benefit/risk ratio at the same time as we conserve drug expenditures. This review discusses the directions we could follow in such a tailored anticoagulation approach, referring to the limited evidence when available.

Topics: Anticoagulants; Cardiovascular Diseases; Humans; Patient Selection; Risk Assessment; Treatment Outcome; Warfarin

Medicine has always been personalized. For years, physicians have incorporated environmental, behavioural, and genetic factors that affect disease and drug response into patient management decisions. However, until recently, the 'genetic' data took the form of family history and self-reported race/ethnicity. As genome sequencing declines in cost, the availability of specific genomic information will no longer be limiting. Rather, our ability to parse these data and our decision whether to use it will become primary. As our understanding of genetic association with drug responses and diseases continues to improve, clinically useful genetic tests may emerge to improve upon our previous methods of assessing genetic risks. Indeed, genetic tests for monogenic disorders have already proven useful. Such changes may usher in a new era of personalized medicine. In this review, we will discuss the utility and limitations of personal genomic data in three domains: pharmacogenomics, assessment of genetic predispositions for common diseases, and identification of rare disease-causing genetic variants.

Topics: Anticoagulants; Cardiovascular Diseases; Clopidogrel; Genetic Predisposition to Disease; Genetic Testing; Genetic Variation; Genome, Human; Humans; Mutation; Neoplasms; Pharmacogenetics; Platelet Aggregation Inhibitors; Precision Medicine; Risk Adjustment; Ticlopidine; Warfarin

The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.

Topics: Administration, Oral; Aged; Anticoagulants; Cardiovascular Diseases; Chronic Disease; Female; Humans; Male; Middle Aged; Perioperative Care; Prognosis; Thromboembolism; Warfarin

Dabigatran etexilate is an oral direct thrombin inhibitor that has been approved by the US Food and Drug Administration for the prevention of stroke and systemic embolization in patients with nonvalvular atrial fibrillation. It has also been studied for the prevention of venous thromboembolism in patients after hip and knee arthroplasty and for treatment of venous thromboembolism. Although routine laboratory monitoring is not needed, there are clinical scenarios in which physicians will need to have a clear understanding of drug pharmacology, laboratory assessment, and reversibility of this drug to make appropriate clinical decisions. We review the pharmacology of dabigatran etexilate, pertinent clinical trials, and the effects of dabigatran etexilate on prothrombin time, activated partial thromboplastin time, thrombin time, and ecarin clotting time. We also provide an approach to patients on dabigatran etexilate who are bleeding, have a suspected therapeutic failure, or require periprocedural management.

Topics: Antithrombins; Benzimidazoles; Blood Coagulation Tests; Cardiovascular Diseases; Clinical Trials as Topic; Dabigatran; Dose-Response Relationship, Drug; Enoxaparin; Humans; Pyridines; Venous Thromboembolism; Warfarin

Arterial and venous thromboembolism account for significant morbidity and mortality worldwide. Warfarin, and other vitamin K antagonists (VKAs), have been the only class of oral anticoagulants currently in clinical use and have been so for over 50 years. Although warfarin is effective in preventing thromboembolism, its use is limited by its narrow therapeutic index that necessitates frequent monitoring and dose adjustments resulting in considerable inconvenience to patients and clinicians. There are now several orally administered anticoagulants in late stages of clinical development that may offer effective, safer, and more convenient anticoagulation. This review summarizes and compares data on novel anticoagulants in the prophylaxis and treatment of venous thromboembolism, acute coronary syndromes, and the prevention of stroke in patients with atrial fibrillation.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Stroke; Thrombin; Thromboembolism; Vitamin K; Warfarin

This review examines ulcers and gastrointestinal bleeding with low-dose aspirin, focusing on randomized placebo-controlled trials. The single endoscopic trial assessing ulcers showed no significant difference in 12-week ulcer incidence: 6% of 381 given placebo vs. 7% of 387 given 81 mg enteric-coated aspirin. The relative risk of major gastrointestinal bleeding with low-dose aspirin in a meta-analysis of placebo-controlled trials of vascular protection was 2.07 (95% CI: 1.61-2.66). The absolute rate increase with aspirin above placebo was 0.12% per year (95% CI: 0.07-0.19%) with a number-needed-to-harm of 833 patients (95% CI: 526-1429). A meta-analysis of aspirin 50-1500 mg daily reported an odds ratio for any gastrointestinal bleeding of 1.68 (95% CI: 1.51-1.88) with an number-needed-to-harm at 1 year of 247. The relative risk of hospitalization for upper gastrointestinal bleeding with low-dose aspirin in a large Danish cohort study was 2.6 (95% CI: 2.2-2.9) with an absolute annual incidence of 0.6%. Factors that may increase the risk of gastrointestinal bleeding include prior history of ulcers or gastrointestinal bleeding, corticosteroid use, anticoagulant therapy and addition of a non-aspirin non-steroidal anti-inflammatory drug. When determining whether low-dose aspirin is appropriate for an individual patient, the cardiovascular benefit must be weighed against the potential for clinical events such as gastrointestinal bleeding.

Topics: Adrenal Cortex Hormones; Aging; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2 Inhibitors; Drug Administration Schedule; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Ulcer; Warfarin

Warfarin and related compounds are efficacious and safe in a variety of clinical thrombotic disorders; however, these drugs have a narrow therapeutic window, whereby inadequate therapy is associated with an increased thrombotic risk and overanticoagulation is associated with bleeding. Therefore, attempts have been made to develop alternatives to warfarin. Ximelagatran, an oral direct thrombin inhibitor, has been shown to be as efficacious and safe as warfarin for the prevention and treatment of different thrombotic disorders. This article reviews the pharmacology of the coumarins, the most commonly used vitamin K antagonists, and the practical aspects regarding their use in the management of thrombotic disorders. The future role of the oral direct thrombin inhibitor ximelagatran also is reviewed.

Topics: Cardiovascular Diseases; Fibrinolytic Agents; Forecasting; Humans; Thrombin; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Models, Chemical; Warfarin

The elderly population is expanding rapidly throughout the world. Hypertension, heart disease and other cardiovascular disorders are prevalent conditions among this age group. Consequently, clinicians will spend a large proportion of their practices managing older adults with cardiovascular disorders. A large proportion of this time will be devoted to using pharmacotherapeutic strategies for the long-term management of chronic conditions. The physiological changes that accompany aging affect cardiovascular function, and the pharmacokinetics and pharmacodynamics of many cardiovascular medications are altered by these physiological changes. The interactions of these changes can have a profound effect on the agents used to treat cardiovascular disorders and may alter their therapeutic outcomes. Several classes of medications are used to treat chronic cardiovascular disorders in older adults. These include the ACE inhibitors and angiotensin II receptor antagonists, calcium channel antagonists, beta-adrenoceptor antagonists (beta-blockers), oral antiarrhythmic agents and warfarin. Drugs such as beta-blockers may aggravate decreased cardiac output and increase peripheral resistance, but are valuable adjuncts in many patients with congestive heart failure. Agents that reduce angiotensin II activity may have several benefits for treating heart failure and hypertension. Successful treatment of cardiovascular disorders in older adults requires the choice of the most appropriate agent, taking into consideration the complex interactions of pharmacokinetics, pharmacodynamics and disease effects.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Calcium Channel Blockers; Cardiovascular Diseases; Humans; Warfarin

In patients suffering from acute myocardial infarction (AMI), new cardiovascular events can be prevented by aspirin or warfarin or a combination of both. Results from studies examining this issue have been published in recent years. We have evaluated the study results together with other factors that are decisive for implementation of the findings in clinical practice.. The following four studies were evaluated: the Coumadin Aspirin Reinfarction Study (CARS); the Combination Hemotherapy and Mortality Prevention (CHAMP) Study; the Warfarin, Aspirin Reinfarction Study (WARIS)-II; the Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT)-2 Study.. The studies had somewhat different design, particularly with regard to the intensity of anticoagulation. CARS and CHAMPS did not show any benefit with combined therapy. WARIS II concluded that warfarin had better preventive effect than aspirin; so had the two drugs in combination. ASPECT-2 suggested a benefit with the combined treatment (coumadin and aspirin) but had limited study power. In all studies, bleedings occurred most frequently in groups of patients treated with anticoagulants. In clinical practice, relatively few AMI patients would be candidates for warfarin treatment, as this drug is not recommended for the oldest patients. Adverse event profile, guidance of treatment and relation to invasive treatment procedures are factors in favour of aspirin.. Aspirin should be the antithrombotic agent of choice in secondary prevention after acute myocardial infarction. Warfarin could be used when there are specific additional indications. Combining these two agents is not recommended as a routine treatment.

Topics: Anticoagulants; Aspirin; Cardiovascular Diseases; Coronary Thrombosis; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Warfarin

The use of oral anticoagulants in the prevention of thrombotics processes, has experienced a considerable increase. In addition, there are a growing experience on the medical and socials consequences of the use of this drug. This has originated a much more pragmatic vision of the daily handling of the anticoagulated patient. In this article, we made are vision about the indications and the practical use, including some useful advices and criteria for the concomitant drug selection.

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Clinical Trials as Topic; Drug Interactions; Humans; Warfarin

THE CONTEXT: The demonstration of the efficacy of oral anticoagulants in the secondary prevention of ischemic stroke represents a major progress in medicine in the last twenty years. Efficacy in fact depends on the causes and this determines the indications. ADMITTED AND DEMONSTRATED INDICATIONS: Cardiac arrhythmia due to atrial fibrillation and the existence of mechanical prosthetic valves are the only two indications that have been demonstrated with sufficient proof. ADMITTED NON-DEMONSTRATED INDICATIONS: These are basically the dissection of cervical arteries, aortal cross atheroma, vascular cerebral accidents within the context of antiphospholipid antibody syndromes. POSSIBLE INDICATIONS: There are three: stenosis of the intra-cranial arteries, patent foramen ovale with atrial septum aneurysm and the basilar dolichoectasia trunks. NON-DEMONSTRATED SUPERIORITY: In atherosclerosis-induced cerebral ischemic accidents.

Topics: Anticoagulants; Antiphospholipid Syndrome; Arteriosclerosis; Aspirin; Atrial Fibrillation; Cardiovascular Diseases; Clinical Trials as Topic; Drug Therapy, Combination; Fibrinolytic Agents; Heart Valve Prosthesis; Humans; Intracranial Arterial Diseases; Platelet Aggregation Inhibitors; Primary Prevention; Retrospective Studies; Risk; Risk Factors; Stroke; Time Factors; Warfarin

Patients with peripheral artery disease suffer from a high incidence of ischemic vascular complications in coronary, cerebral, and peripheral vascular beds. Reduction of atherothrombotic complications with aspirin or clopidogrel has proven to be successful. The role of oral anticoagulants in patients with symptomatic peripheral artery is limited. Randomized controlled trials comparing the effects of aspirin with oral anticoagulants are scarce. Oral anticoagulants (International Normalized Ratio = 2.5 to 4.5) are more effective than aspirin in preventing infrainguinal bypass occlusion only when venous graft material is used and the bypass is considered to be at high risk for occlusion. Whether the use of oral anticoagulants reduces all-cause morbidity and mortality is not unequivocally clear. The risk of ischemic events is reduced at the expense of an increased number of bleeding complications, which is one of the main reasons that therapy has not been widely adopted.

Topics: Administration, Oral; Anticoagulants; Arterial Occlusive Diseases; Cardiovascular Diseases; Humans; Peripheral Vascular Diseases; Vascular Surgical Procedures; Warfarin

The recommendations of the Fifth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy are reviewed, with a focus on outpatient anticoagulation management in adults. Numerous therapeutic recommendations have changed since the Fourth ACCP Consensus Conference on Antithrombotic Therapy. The system of grading recommendations has been modified to emphasize clinically important differences and to take into account the benefit-risk ratio of each treatment option. The International Normalized Ratio (INR) goal is now expressed as a specific target value within a range rather than simply an INR range. The recommendations of the fifth conference cover initiation of warfarin therapy, hemorrhagic complications, management of excessive anticoagulation, interruption of warfarin therapy for patients requiring surgery, nonvalvular atrial fibrillation, cardioversion in patients with atrial fibrillation, valvular heart disease, mechanical and biological prosthetic heart valves, coronary artery disease, saphenous vein and internal mammary artery bypass grafts, peripheral arterial occlusive disease, prevention of venous thromboembolism, treatment of venous thromboembolism, stroke prevention in patients with cerebrovascular disease, and pregnancy. Since the fourth consensus conference, new anticoagulation therapies and indications have emerged; the recommendations of the Fifth ACCP Consensus Conference on Antithrombotic Therapy have provided practitioners with a resource of immense value.

Topics: Adult; Aged; Anticoagulants; Association; Cardiovascular Diseases; Fibrinolytic Agents; Humans; Middle Aged; Outpatients; Thrombosis; Warfarin

Topics: Aged; Aged, 80 and over; Anemia; Atrial Fibrillation; Cardiovascular Diseases; Family Practice; Female; Humans; Hypertension; Life Style; Male; Warfarin

Activated thrombin plays a central role thrombosis and in hemostasis, both by controlling the coagulation process, and by activating receptors on platelets and various cell types. A safe and effective inhibitor of thrombin active site could be a useful tool in the treatment of venous thrombosis, atrial fibrillation, restenosis, arterial thrombosis, and in the prevention of myocardial infarction. Because of this, the modulation of thrombin by direct, small molecule inhibitors is a widely sought goal in the pharmaceutical industry. However, this search has thus far proved elusive. Criteria for a pharmaceutically acceptable thrombin inhibitor include high and reproducible bioavailability, selectivity, and a long duration of action. The profile of currently researched thrombin active site inhibitors is discussed in relation to these goals.

Topics: Amino Acid Sequence; Anticoagulants; Binding Sites; Biological Availability; Cardiovascular Diseases; Drug Design; Humans; Molecular Sequence Data; Pharmacokinetics; Thrombin; Warfarin

Optimizing anticoagulation and hemostasis during cardiopulmonary bypass and perioperatively helps to ensure the best possible clinical outcome. This article reviews the pharmacology of unfractionated and low-molecular weight heparin, aprotinin, desmopressin, dextran, antiplatelet agents, warfarin, and direct thrombin inhibitors. Their use is discussed in the context of coronary artery surgery, valvular surgery, and mechanical cardiac support devices, as well as in the management of acute ischemic syndromes, atrial fibrillation, and prevention and treatment of venous thromboembolism. Progress in the development and utilization of these anticoagulants and antiplatelet agents has supported the major advances that have been achieved in cardiac surgery.

Topics: Anticoagulants; Cardiac Surgical Procedures; Cardiovascular Diseases; Hemostasis, Surgical; Heparin; Humans; Platelet Aggregation Inhibitors; Protamines; Warfarin

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Female; Heart Valve Prosthesis; Humans; Pregnancy; Vitamin K; Warfarin

Anticoagulation therapy continues to evolve as more precise indications for its use are recognized. With adoption of the international normalized ratio, safer and more effective application is in the offing. Newer uses are discussed.

Topics: Anticoagulants; Cardiovascular Diseases; Heparin; Humans; Pulmonary Embolism; Thrombophlebitis; Warfarin

Although several large trials have failed to demonstrate unequivocally that anticoagulation decreases mortality following myocardial infarction (MI), anticoagulation has been advocated to prevent embolic cerebrovascular accidents (CVAs). Since CVAs occur during hospitalization in only 1.5% to 3% of MIs, it is not justifiable to anticoagulate all patients after MI because the risk of anticoagulation exceeds the potential benefit. However, a group of patients who are at high risk of developing left ventricular thrombi (LVT) and CVA following MI can be identified. Thirty percent to 40% of patients with transmural anterior MI develop LVT, and early anticoagulation with heparin sodium prevents LVT formation and CVAs in this group. A two-dimensional echocardiogram before hospital discharge allows the identification of patients at risk for later embolization and helps determine the need for anticoagulation with warfarin sodium following hospitalization.

Topics: Cardiovascular Diseases; Echocardiography; Heart Diseases; Heparin; Humans; Length of Stay; Myocardial Infarction; Risk; Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Mitral Valve; Myocardial Infarction; Rheumatic Heart Disease; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Female; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Pyridines; Risk Assessment; Risk Factors; Thiazoles; Time Factors; Treatment Outcome; Warfarin

The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain.. In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months.. A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups.. In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).

Topics: Aged; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Cardiovascular Diseases; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Rivaroxaban; Single-Blind Method; Stroke; Warfarin

This study assessed baseline cardiovascular (CV) risk factors, concomitant CV medication use, risk of major adverse cardiac events-plus (MACE-plus), and bleeding adverse events (AEs) in patients with idiopathic pulmonary fibrosis (IPF) in three randomized, placebo-controlled phase III trials of pirfenidone.. Patients in the pirfenidone phase III trials were included. Patients with unstable or deteriorating cardiac disease within 6 months before enrollment were ineligible. Medical history at baseline and concomitant CV medication use during treatment were reported. A retrospective, blinded review of AE preferred terms was conducted to identify MACE-plus and bleeding events. Subgroup analyses examined the impact of concomitant CV medication use on how pirfenidone treatment affected clinical outcomes.. In total, 1247 patients were included [n = 623 pirfenidone (2403 mg/day) and n = 624 placebo]. The median age was 68 years, 74% were male, and 65% were current/former smokers. Commonly reported CV risk factors included hypertension (52%), obesity (44%), hypercholesterolemia (23%), and hyperlipidemia (23%). Pre-existing cardiac disorders included coronary artery disease (16%), myocardial infarction (5%), and atrial fibrillation (5%). Lipid-modifying agents (60%), antithrombotic agents (54%), and renin-angiotensin inhibitors (39%) were commonly used concomitant CV medications. The incidences of MACE-plus and bleeding events were similar between the pirfenidone and placebo groups (1.8% and 2.9% for MACE-plus events and 3.7% and 4.3% for bleeding events, respectively). Except for patients receiving heparin, pirfenidone had a beneficial effect compared with placebo on efficacy outcomes regardless of concomitant CV medications.. CV risk factors and comorbidities and use of concomitant CV medications are common in patients with IPF. Pirfenidone did not appear to increase the risk of CV or bleeding events. Use of several concomitant CV medications, including warfarin, did not appear to adversely impact pirfenidone's beneficial effect on efficacy outcomes.. NCT00287716, NCT00287729, and NCT01366209.. F. Hoffmann-La Roche Ltd. and Genentech, Inc.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Atrial Fibrillation; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Disease; Female; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Pyridones; Retrospective Studies; Risk Factors; Treatment Outcome; Warfarin

Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding.. Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography.. A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25-3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23-6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71-6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus.. In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cardiovascular Diseases; Double-Blind Method; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Plaque, Atherosclerotic; Pyrazoles; Pyridones; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Warfarin

To evaluate the association between use of antiplatelet or anticoagulant drugs and retinal or subretinal hemorrhage in participants with neovascular age-related macular degeneration (AMD) in the Comparison of AMD Treatments Trials (CATT).. Cohort study within CATT.. Participants in CATT with untreated active neovascular AMD (n = 1185).. Participants were interviewed for use of antiplatelet or anticoagulant drugs. Trained readers evaluated photographs for the presence and size of retinal or subretinal hemorrhage at baseline and years 1 and 2. Associations between use of antiplatelet or anticoagulant drugs and hemorrhage were evaluated among all participants and by baseline hypertension status using multivariate logistic regression models.. Odds ratio for association with antiplatelet or anticoagulant use.. Among 1165 participants with gradable photographs, 724 (62.1%) had retinal or subretinal hemorrhage at baseline; 84.4% of hemorrhages were 1 disc area (DA) or less, 8.1% were 1 to 2 DA, and 7.5% were more than 2 DA. At baseline, 608 participants (52.2%) used antiplatelet or anticoagulant drugs, including 514 participants (44.1%) using antiplatelets only, 77 (6.6%) using anticoagulants only, and 17 (1.5%) using both. Hemorrhage was present in 64.5% of antiplatelet or anticoagulant users and in 59.6% of nonusers (P = 0.09; adjusted odds ratio [OR], 1.18; 95% confidence interval, 0.91-1.51; P = 0.21). Neither presence nor size of baseline hemorrhage was associated with the type, dose, or duration of antiplatelet or anticoagulant use. Forty-four of 1078 participants (4.08%) had retinal or subretinal hemorrhage detected on 1- or 2-year photographs; these hemorrhages were not associated with antiplatelet or anticoagulant use at baseline (P = 0.28) or during follow-up (P = 0.64). Among participants with hypertension (n = 807), antiplatelet or anticoagulant use was associated with a higher rate of hemorrhage at baseline (66.8% vs. 56.4%; adjusted OR, 1.48; P = 0.01), but not size of retinal or subretinal hemorrhage (P = 0.41).. Most retinal or subretinal hemorrhages in eyes enrolled in CATT were less than 1 DA. Among all CATT participants, antiplatelet or anticoagulant use was not associated significantly with hemorrhage, but it was associated significantly with hemorrhage in participants with hypertension.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Anticoagulants; Aspirin; Bevacizumab; Cardiovascular Diseases; Clopidogrel; Female; Fluorescein Angiography; Humans; Hypertension; Intravitreal Injections; Male; Odds Ratio; Platelet Aggregation Inhibitors; Ranibizumab; Retinal Hemorrhage; Risk Factors; Ticlopidine; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Warfarin; Wet Macular Degeneration

Obesity has been associated with increased cardiovascular risk in atrial fibrillation, but little is known in elderly patients with atrial fibrillation.. Post hoc analysis of data from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial.. We studied 1588 elderly patients, who were categorized as normal body mass index (BMI, 18.5-25 kg/m(2); n=515 [32.4%]), overweight (BMI, 25-30 kg/m(2); n=711 [44.8%]), and obese (BMI≥30 kg/m(2); n=362 [22.8%]). There was a significant reduction in the composite outcome of cardiovascular death and stroke/systemic embolism with increasing BMI category, being 5.0%, 3.2%, and 1.5% per 100 patient-years, respectively (P for trend=0.01). Cox proportional hazards analysis found obesity to be associated with a lower risk of the primary composite outcome (hazard ratio, 0.29; 95% confidence interval, 0.11-0.77; P=0.01). In the warfarin arm (n=814), multivariate logistic regression analysis demonstrated that obesity was independently related to higher odds of time in therapeutic range ≥60% (odds ratio, 1.84; 95% confidence interval, 1.21-2.80; P=0.004).. Obesity was associated with a lower stroke and mortality rate in elderly anticoagulated atrial fibrillation patients. Obesity was related to good quality anticoagulation control.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Humans; Logistic Models; Male; Multivariate Analysis; Obesity; Oligosaccharides; Overweight; Proportional Hazards Models; Risk Factors; Stroke; Warfarin

Oral anticoagulants are widely prescribed drugs. Interruption of anticoagulant therapy prior to oral surgery has been an issue of great controversy. The purpose of this study was to evaluate the incidence of bleeding complications after dental extractions in patients on anticoagulant therapy (warfarin) in whom different local hemostatic methods were used.. Patients using warfarin and requiring extractions of at least two teeth were screened to participate in this prospective, randomized study. Extraction sites were considered as sampling units (statistically representative sample size) and were allocated to one of the three study groups (G1-4.8% tranexamic acid; G2-fibrin sponge; and G3-no local hemostatic agents).. Eighty-four extraction sites were obtained from patients with mitral valve prolapse (47.4%), prosthetic cardiac valve (23.7%), venous thromboembolism (21.1%), and pulmonary embolism (5.2%). International normalized ratio (INR) values ranged between 2.1 and 3.1 (mean 2.51 ± 0.1). Postoperative bleeding was observed in four surgical sites (p < 0.001) and was mainly in older patients (p = 0.005).. The three local hemostatic protocols were similarly effective in controlling postoperative bleeding in patients undergoing anticoagulant therapy with warfarin. The majority of teeth could be extracted with minimal problems in patients with cardiovascular diseases receiving treatment with anticoagulant therapy.

Topics: Administration, Topical; Adult; Aged; Anticoagulants; Brazil; Cardiovascular Diseases; Female; Fibrin Tissue Adhesive; Hemostatic Techniques; Humans; Male; Middle Aged; Postoperative Hemorrhage; Pressure; Prospective Studies; Surgical Sponges; Tooth Extraction; Tranexamic Acid; Warfarin

We designed a prospective, randomized, open-label, blinded end point evaluation parallel group Phase 3b clinical trial comparing edoxaban (a new oral factor Xa inhibitor) with enoxaparin/warfarin followed by warfarin alone in subjects undergoing planned electrical cardioversion of non-valvular atrial fibrillation. The primary efficacy end point is the composite end points of stroke, systemic embolic event, myocardial infarction, and cardiovascular (CV) mortality, from randomization until the end of follow-up (day 56 post cardioversion). The primary safety end point is the composite of major and clinically-relevant non-major bleeding, from the first administration of study drug to end of treatment (Day 28 post cardioversion) +3 days. The primary efficacy analysis will be conducted on the intention-to-treat population whereas the primary safety analysis, on the safety population. The study includes stratification on the following levels: (i) approach to cardioversion (transoesophagel echocardiography or non-transoesophagel echocardiography) as determined by the Investigator; (ii) subject's experience in taking anticoagulants at the time of randomization (anticoagulant-experienced or anticoagulant-naïve); and (iii) assigned edoxaban dose (full 60 mg QD or reduced 30 mg dose QD). A subject with one or more factors (CrCl ≥15 mL/min and ≤50 mL/min, low body weight [≤60 kg], and concomitant use of p-pg inhibitors (excluding amiodarone) will receive a reduced dose (30 mg) of edoxaban if the subject is randomized to the edoxaban group. ENSURE-AF will be the largest prospective randomised trial of anticoagulation for cardioversion, also involving a Non-VKA Oral Anticoagulant-edoxaban.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Electric Countershock; Factor Xa Inhibitors; Female; Humans; Male; Prospective Studies; Pyridines; Research Design; Stroke; Thiazoles; Thromboembolism; Warfarin

While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions.. To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin.. PROTECT AF was a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2 score ≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5% and superiority a probability of 95% or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups.. Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3).. A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat.. At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95% credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, >99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95% CI, 0.21-0.75; P = .005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95% CI, 0.45-0.98; P = .04).. After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.. clinicaltrials.gov Identifier: NCT00129545.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Bayes Theorem; Cardiac Catheterization; Cardiovascular Diseases; Embolism; Female; Humans; Male; Middle Aged; Prosthesis Implantation; Risk Factors; Stroke; Survival Analysis; Treatment Outcome; Warfarin

Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known.. We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding.. The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32).. Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Double-Blind Method; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pyridines; Stroke; Thiazoles; Warfarin

Patients having undergone femoropopliteal bypass surgery remain at significant risk of graft failure. Although antithrombotic therapy is of paramount importance in these patients, the effect of oral anticoagulation therapy (OAT) on outcomes remains unresolved. We performed a randomized, prospective study to assess the impact of OAT plus clopidogrel vs dual antiplatelet therapy on peripheral vascular and systemic cardiovascular outcomes in patients who had undergone femoropopliteal bypass surgery.. Three hundred forty-one patients who had undergone femoropopliteal surgery were enrolled and randomized: 173 patients received clopidogrel 75 mg/d plus OAT with warfarin (C + OAT), and 168 patients received dual antiplatelet therapy with clopidogrel 75 mg/d plus aspirin 100 mg/d (C + acetylsalicylic acid [ASA]). Study end points were graft patency and the occurrence of severe peripheral arterial ischemia, and the incidence of bleeding episodes.. Follow-up ranged from 4 to 9 years. The graft patency rate and the freedom from severe peripheral arterial ischemia was significantly higher in C + OAT group than in C + ASA group (P = .026 and .044, respectively, Cox-Mantel test). The linearized incidence of minor bleeding complications was significantly higher in C + OAT group than in C + ASA group (2.85% patient-years vs 1.37% patient-years; P = .03). The incidence of major adverse cardiovascular events, including mortality, was found to be similar (P = .34) for both study groups.. In patients who have undergone femoropopliteal vascular surgery, combination therapy with clopidogrel plus warfarin is more effective than dual antiplatelet therapy in increasing graft patency and in reducing severe peripheral ischemia. These improvements are obtained at the expenses of an increase in the rate of minor anticoagulation-related complications.

Topics: Administration, Oral; Aged; Aspirin; Cardiovascular Diseases; Chi-Square Distribution; Clopidogrel; Comorbidity; Drug Therapy, Combination; Female; Femoral Artery; Graft Occlusion, Vascular; Humans; Logistic Models; Male; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Popliteal Artery; Proportional Hazards Models; Prospective Studies; Ticlopidine; Treatment Outcome; Vascular Patency; Warfarin

Poor adherence to medications is a major cause of morbidity and inadequate drug effectiveness. Efforts to improve adherence have typically been either ineffective or too complex to implement in clinical practice. Lottery-based incentive interventions could be a scalable approach to improving adherence.. This was a randomized, controlled clinical trial of a daily lottery-based incentive in patients on warfarin stratified by baseline international normalized ratio (INR). The trial randomized 100 patients to either a lottery-based incentive or no lottery intervention. Main outcome was out-of-range INRs.. Over 6 months, the overall percentage of out-of-range INRs did not differ between the 2 arms (mean 23.0% in lottery arm and 25.9% in control arm, adjusted odds ratio [OR] 0.93, 95% CI 0.62-1.41). However, among the a priori subgroup with a baseline INR below therapeutic range, there was a significant reduction in out-of-range INR in the lottery arm versus the control arm (adjusted OR 0.39, 95% CI 0.25-0.62), whereas there was no such effect among those with therapeutic INRs at baseline (adjusted OR 1.26, 95% CI, 0.76-2.09, P value for interaction = .0016). Among those with low INR at baseline, there was a nonsignificant 49% reduction in the odds of nonadherence with the intervention (OR 0.51, 95% CI 0.23-1.14).. Although a lottery-based intervention was not associated with a significant improvement in anticoagulation control among all study participants, it improved control among an a priori group of patients at higher risk for poor adherence.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Female; Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Motivation; Thromboembolism; Warfarin

In patients with myeloma, thalidomide significantly improves outcomes but increases the risk of thromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin (ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens.. A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were randomly assigned to receive ASA (100 mg/d), WAR (1.25 mg/d), or LMWH (enoxaparin 40 mg/d). A composite primary end point included serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment.. Of 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascular events, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WAR group, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were +1.3% (95% CI, -3.0% to 5.7%; P = .544) in the ASA group and +3.2% (95% CI, -1.5% to 7.8%; P = .183) in the WAR group. The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%) bleeding episodes were recorded.. In patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similar efficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deaths compared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.

Topics: Aged; Anticoagulants; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aspirin; Cardiovascular Diseases; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Humans; Italy; Male; Middle Aged; Multiple Myeloma; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Thalidomide; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation.. The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking).. The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation.

Topics: Aged; Alcohol Drinking; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Asian People; Cardiovascular Diseases; Cohort Studies; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; International Normalized Ratio; Japan; Male; Middle Aged; Mixed Function Oxygenases; Pharmacogenetics; Polymorphism, Genetic; Smoking; Vitamin K Epoxide Reductases; Warfarin

To determine the influence of a positive genetic test for hypertrophic cardiomyopathy (HCM) on clinical outcome.. A cohort of 203 unrelated patients with HCM (mean +/- SD age, 50+/-18 years) was enrolled from January 1, 2002, through December 31, 2003. They were followed up for a mean +/- SD time of 4.0+/-1.7 years after genetic testing of the 8 HCM-susceptibility genes that encode key sarcomeric/myofilament proteins. The clinical phenotype of those with a positive genetic test (myofilament-positive HCM) was compared with those with a negative genetic test (myofilament-negative HCM).. In this cohort of 203 patients, 87 mutations were identified in 126 patients (myofilament-positive HCM, 62%); the remaining 77 patients (38%) were myofilament-negative. Despite similar baseline features, patients with myofilament-positive HCM showed increased risk of the combined end points of cardiovascular death, nonfatal stroke, or progression to New York Heart Association class III or IV compared with the patients with myofilament-negative HCM (25% vs 7%, respectively; independent hazard ratio, 4.27; P=.008). These end points occurred at any age among patients with myofilament-positive HCM (range, 14-86 years), but only in those aged 65 years and older among patients with myofilament-negative HCM. Moreover, patients with myofilament-positive HCM showed greater probability of severe left ventricular systolic and diastolic dysfunction, defined as an ejection fraction of less than 50% and a restrictive filling pattern (P=.02 and P<.02, respectively, vs myofilament-negative HCM).. Screening for sarcomere protein gene mutations in HCM identifies a broad subgroup of patients with increased propensity toward long-term impairment of left ventricular function and adverse outcome, irrespective of the myofilament (thick, intermediate, or thin) involved.

Topics: Actin Cytoskeleton; Adult; Aged; Anticoagulants; Cardiomyopathy, Hypertrophic; Cardiovascular Diseases; Carrier Proteins; Cohort Studies; Coronary Artery Bypass; Endpoint Determination; Female; Genetic Testing; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Ultrasonography; Warfarin

Point-of-care (POC) anticoagulation testing devices can potentially improve warfarin therapeutics in long-term care; however, there is variable accuracy reported for these devices and scant data when used in older adults. Accordingly, we undertook this study to determine the accuracy of a POC device (Hemosense INratio) in long-term care settings and examine factors associated with discrepant results.. Case series.. Two, demographically comparable continuing-care retirement communities in the Southeastern United States.. Long-term (nursing home and assisted living) residents with atrial fibrillation, venous thromboembolism, or prior cerebrovascular accident (16 at site 1; 8 at site 2).. INR results calculated by the Hemosense device were compared with those determined by venipuncture-collected samples run in commercial laboratories. Patient demographic and clinical data were collected, as was performance by tester.. Correlation varied between sites and, at site 1, between testers. Accuracy at site 1 was comparable to published reports for 2 of the 3 testers, with rather disconcerting discrepancy rates of 17.8% and 23.1%. However, correlation for the third tester was much better, with only a 7% discrepancy rate based on clinician rating of Hemosense-Reference lab differences. Correlation at site 2 was considerably worse than site 1, to the point that the Hemosense could not be safely adopted.. POC devices may not be appropriate for commercial laboratory tests substitution without prior performance evaluation. Running POC INRs concurrent with laboratory-determined INRS can determine test reliability. Timing of Hemosense testing in relation to when laboratory INRs were drawn is one likely explanation for our results, although user differences may also contribute significantly. Further research in larger, more diverse populations, using a variety of POC devices, and with direct comparison of older and younger patients is needed.

Topics: Aged, 80 and over; Anticoagulants; Assisted Living Facilities; Cardiovascular Diseases; Equipment and Supplies; Female; Humans; International Normalized Ratio; Long-Term Care; Male; Nursing Homes; Point-of-Care Systems; Southeastern United States; Warfarin

Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes. Antiplatelet drugs reduce this risk, but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear.. We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent (target international normalized ratio [INR], 2.0 to 3.0) or to antiplatelet therapy alone. The first coprimary outcome was myocardial infarction, stroke, or death from cardiovascular causes; the second coprimary outcome was myocardial infarction, stroke, severe ischemia of the peripheral or coronary arteries leading to urgent intervention, or death from cardiovascular causes.. A total of 2161 patients were randomly assigned to therapy. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (relative risk, 0.92; 95% confidence interval [CI], 0.73 to 1.16; P=0.48). Myocardial infarction, stroke, severe ischemia, or death from cardiovascular causes occurred in 172 patients receiving combination therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (relative risk, 0.91; 95% CI, 0.74 to 1.12; P=0.37). Life-threatening bleeding occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (relative risk, 3.41; 95% CI, 1.84 to 6.35; P<0.001).. In patients with peripheral arterial disease, the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding. (ClinicalTrials.gov number, NCT00125671 [ClinicalTrials.gov].).

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aspirin; Atherosclerosis; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Interventions to promote prescribing of preventive therapies in patients with cardiovascular disease (CVD) or diabetes have reported variable success.. (i) To evaluate the effect of prescribing feedback on GP practice using academic detailing compared to postal bulletin on prescribing of CVD preventive therapies in patients with CVD or diabetes at 3 and 6 months post intervention and (ii) to evaluate the intervention from a GP's perspective.. Volunteer GP practices (n = 98) were randomized to receive individualized prescribing feedback via academic detailing (postal bulletin plus outreach visit) (n = 48) or postal bulletin (n = 50). The proportion of CVD or diabetic patients on statins and antiplatelet agents/warfarin pre- and post-intervention was calculated for each GP practice. Multivariate regression with a random effects model was used to compare differences between the groups adjusting for GP clustering and confounding factors. beta-Coefficients and 95% confidence intervals (CIs) are presented.. There was a 3% increase in statin prescribing in CVD patients at 6 months post-intervention for both randomized groups, but there was no statistical difference between the groups (beta = 0.004; 95% CI = -0.01 to 0.02). Statin and antiplatelet/warfarin prescribing also increased in the diabetic population; there was no significant differences between the groups. GPs participating in the project expressed a high level of satisfaction with both interventions.. Prescribing of preventive therapies increased in both randomized groups over the study period. But academic detailing did not have an additional effect on changing prescribing over the postal bulletin alone.

Topics: Anticoagulants; Attitude of Health Personnel; Cardiovascular Diseases; Cluster Analysis; Diabetes Complications; Drug Utilization Review; Education, Medical, Continuing; Feedback, Psychological; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Physicians, Family; Platelet Aggregation Inhibitors; Postal Service; Practice Patterns, Physicians'; Program Evaluation; Warfarin

Atherosclerotic intracranial arterial stenosis is an important cause of stroke. Warfarin is commonly used in preference to aspirin for this disorder, but these therapies have not been compared in a randomized trial.. We randomly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin (target international normalized ratio, 2.0 to 3.0) or aspirin (1300 mg per day) in a double-blind, multicenter clinical trial. The primary end point was ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke.. After 569 patients had undergone randomization, enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin. During a mean follow-up period of 1.8 years, adverse events in the two groups included death (4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group; hazard ratio for aspirin relative to warfarin, 0.46; 95 percent confidence interval, 0.23 to 0.90; P=0.02), major hemorrhage (3.2 percent vs. 8.3 percent, respectively; hazard ratio, 0.39; 95 percent confidence interval, 0.18 to 0.84; P=0.01), and myocardial infarction or sudden death (2.9 percent vs. 7.3 percent, respectively; hazard ratio, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.02). The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group (P=0.16); the rate of death from nonvascular causes was 1.1 percent and 3.8 percent, respectively (P=0.05). The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group (hazard ratio, 1.04; 95 percent confidence interval, 0.73 to 1.48; P=0.83).. Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial. Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis.

Topics: Adult; Aged; Anticoagulants; Aspirin; Cardiovascular Diseases; Double-Blind Method; Female; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Secondary Prevention; Stroke; Warfarin

There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care.. We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range +/- 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups.. Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians (p = 0.001).. Anticoagulation clinics provided better oral anticoagulant management than family physicians, but the differences were relatively modest.

Topics: Ambulatory Care Facilities; Anticoagulants; Cardiovascular Diseases; Confidence Intervals; Endpoint Determination; Female; Humans; International Normalized Ratio; Male; Middle Aged; Physicians, Family; Prospective Studies; Quality of Health Care; Thromboembolism; Treatment Outcome; Warfarin

In the Coumadin Aspirin Reinfarction Study (CARS), the primary (efficacy) endpoint was time to the first occurrence of reinfarction, ischemic stroke, or cardiovascular death. Study events likely to be a component of the primary endpoint were reviewed by a blinded Events Classification Committee (ECC). To accommodate the inherent delay imposed by the adjudication process, we used the results of prior adjudication to predict classifications for selected unadjudicated study events in order to conduct "up-to-date" interim analyses for the Data and Safety Monitoring Committee (DSMC). Rates at which previously adjudicated study events were confirmed as primary event components were used to adjust the Kaplan-Meier estimates of survival and the log-rank statistics. Multiple events for a given subject were weighted according to the probability that prior events would be confirmed. Once all study events were adjudicated, final analyses confirmed the results of the adjusted interim analysis. For monitoring clinical trials with adjudicated endpoint events, models based on prior adjudication histories can be reliably used to predict event classifications for unadjudicated events and support accurate, contemporary interim analyses.

Topics: Anticoagulants; Cardiovascular Diseases; Data Interpretation, Statistical; Humans; Logistic Models; Models, Statistical; Randomized Controlled Trials as Topic; Survival Analysis; Warfarin

There is an increasing use of computer-based dosage programs to monitor oral anticoagulant therapy in outpatients. DAWN AC INDUCTION by 4S, UK, is a computer generated system to initiate oral anticoagulant therapy providing fast access to the maintenance program. This method of initiation of anticoagulant therapy has not been validated. We therefore randomized 50 hospitalized patients starting oral anticoagulation to control by the computer and 51 by manual dosing using a dosing schedule based on a locally defined algorithm. After a 7 days follow up, the daily mean INR was 2.09 and 2.07 and the proportion of dose adjustments was 48% and 45% in the computer and manually controlled groups respectively. Twenty-eight % of the patients monitored by the computer system required at least one manual overriding. DAWN AC INDUCTION provided a simple and accurate organization of the data, with an overall quality comparable to that of the manual system. Furthermore, the induction programme provided simple access to the maintenance programme. Although it required careful monitoring, the programme resulted in a significant saving in personnel time.

Topics: Administration, Oral; Algorithms; Anticoagulants; Cardiovascular Diseases; Drug Hypersensitivity; Drug Therapy, Computer-Assisted; Female; Heparin; Hospitalization; Humans; International Normalized Ratio; Male; Middle Aged; Warfarin

We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction.. Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial.. We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome.. On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology.. In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.

Topics: Angina, Unstable; Anticoagulants; Cardiac Output, Low; Cardiovascular Diseases; Cause of Death; Cohort Studies; Female; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Ventricular Dysfunction, Left; Warfarin

In this study the warfarin level in the plasma of 60 patients receiving different dosage regimens of warfarin were determined by HPLC. The corresponding prothrombin times (PT) were also measured. The steady state plasma level of warfarin in 10 healthy volunteers was 900.7+/-158.21 ng/ml. A mean dose of 3.79+/-1.02 mg of warfarin corresponded to a therapeutic level of 1193.81+/-300.35 ng/ml with a mean PT of 20.13+/-0.69 s. The results of this study suggest that Iranian subjects are more sensitive to warfarin than North American and European subjects, but have responses very similar to those of Asians. Dietary, ethnic and geographical factors as well as differences in drug dispensition may be the cause of the observed dosage variability of warfarin.

Topics: Adult; Asia; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Europe; Female; Humans; Iran; Male; Middle Aged; North America; Prothrombin Time; Warfarin

To explore whether antithrombotic medication may protect against cognitive decline, tests of verbal memory, attention, abstract reasoning, verbal fluency, and mental flexibility were administered to 405 men at risk of cardiovascular disease. These subjects were a subgroup of those who had been participating in a randomised double blind factorial trial of low dose aspirin (75 mg daily) and low intensity oral anticoagulation with warfarin (international normalised ratio of 1.5) at 35 general practices across the United Kingdom for at least five years, were at least 55 years old at trial entry, and had been randomly allocated to one of four groups: active warfarin and active aspirin, active warfarin and placebo aspirin, placebo warfarin and active aspirin, and double placebo. Verbal fluency and mental flexibility were significantly better in subjects taking antithrombotic medication than in subjects taking placebo. Aspirin may have contributed more than warfarin to any beneficial effect. These results provide tentative evidence that antithrombotic medication may protect cognitive function in men at risk of cardiovascular disease.

Topics: Aged; Anticoagulants; Aspirin; Cardiovascular Diseases; Cognition; Cognition Disorders; Double-Blind Method; Humans; Male; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Antiplatelet therapy with aspirin and systematic anticoagulation with warfarin reduce cardiovascular morbidity and mortality after myocardial infarction when given alone. In the Coumadin Aspirin Reinfarction Study (CARS), we aimed to find out whether a combination of low-dose warfarin and low-dose aspirin would give superior results to standard aspirin monotherapy without excessive bleeding risk.. We used a randomised double-blind study design. At 293 sites, we randomly assigned 8803 patients who had had myocardial infarction, treatment with 160 mg aspirin, 3 mg warfarin with 80 mg aspirin, or 1 mg warfarin with 80 mg aspirin. Patients took a single tablet daily, and attended for prothrombin time (PT) measurements at weeks 1, 2, 3, 4, 6, and 12, and then every 3 months. Patients were followed up for a maximum of 33 months (median 14 months).. The primary event was first occurrence of reinfarction, non-fatal ischaemic stroke, or cardiovascular death. 1-year life-table estimates for the primary event were 8.6% (95% CI 7.6-9.6) for 160 mg aspirin, 8.4% (7.4-9.4) for 3 mg warfarin with 80 mg aspirin, and 8.8% (7.6-10) for 1 mg warfarin with 80 mg aspirin. Primary comparisons were done with all follow-up data. The relative risk of the primary event for the 160 mg aspirin group compared with the 3 mg warfarin with 80 mg aspirin group was 0.95 (0.81-1.12, p = 0.57). For spontaneous major haemorrhage (not procedure related), 1-year life-table estimates were 0.74% (0.43-1.1) in the 160 mg aspirin group and 1.4% (0.94-1.8) in the 3 mg warfarin with 80 mg aspirin group (p = 0.014 log rank on follow-up). For the 3382 patients assigned 3 mg warfarin with 80 mg aspirin, the INR results were: at week 1 (n = 2985) median 1.51 (IQR 1.23-2.13); at week 4 (n = 2701) 1.27 (1.13-1.64); at month 6 (n = 2145) 1.19 (1.08-1.44).. Low, fixed-dose warfarin (1 mg or 3 mg) combined with low-dose aspirin (80 mg) in patients who have had myocardial infarction does not provide clinical benefit beyond that achievable with 160 mg aspirin monotherapy.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Cardiovascular Diseases; Diabetes Complications; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Myocardial Infarction; Risk; Treatment Outcome; Warfarin

To investigate the effect of warfarin treatment on the early phase of tissue factor-induced coagulation, we measured plasma-activated factor VII (factor VIIa) levels by a direct fluorogenic assay in 74 cardiovascular disease patients on long-term oral anticoagulation. We divided the patients into three groups based on the international normalized ratio (INR). In the patients with INR ranges of < 1.7 and 1.7 to 2.5, factor VIIa levels were 42% and 61% lower, respectively, than in age- and sex-matched controls. Factor VII coagulant activity (factor VIIc), factor VII antigen (factor VIIag), protein C, and factor X levels were also reduced to a similar extent in both groups. However, in patients with an INR > 2.5, the factor VIIa level was not decreased compared with that at an INR of 1.7 to 2.5, although the factor VIIc, factor VIIag, factor X, and protein C levels were all decreased further. Although the precise relation between the reduction of factor VIIa levels and the increase of INR requires appropriately designed long-term clinical trials, our data suggest that an INR range of 1.7 to 2.5 is sufficient for the suppression of factor VIIa. During the long-term follow-up of three patients with congenital antithrombin III or protein C deficiency, the factor VIIa level was more responsive to changes in the warfarin dose than the INR, and there were generally no corresponding changes of the thrombin-antithrombin III complex (TAT) level. However, one patient showed a transient marked increase of factor VIIa during the discontinuation of warfarin that was accompanied by an increase in TAT. Based on these findings, factor VIIa could be useful for monitoring both hypercoagulable and hypocoagulable states.

Topics: Adult; Aged; Antithrombin III Deficiency; Biomarkers; Cardiovascular Diseases; Factor VIIa; Female; Humans; Male; Middle Aged; Protein C Deficiency; Warfarin

HMG CoA reductase inhibitors (or statins), a new class of lipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they more effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease.. Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial with factorial design along with warfarin (1 mg/d) or its placebo. This report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 919 asymptomatic men and women, 40 to 79 years old, with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3-year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the carotid arteries was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups. Among participants not on warfarin, regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was statistically significant (P = .001). A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant (P = .12). Five lovastatin-treated participants suffered major cardiovascular events--coronary heart disease mortality, nonfatal myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P = .04). One lovastatin-treated participant died, compared with eight on lovastatin-placebo (P = .02).. In men and women with moderately elevated LDL cholesterol, lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality. Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins.

Topics: Adult; Aged; Arteriosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Double-Blind Method; Female; Humans; Lovastatin; Male; Middle Aged; Risk Factors; Survival Analysis; Tunica Intima; Tunica Media; Ultrasonography; Warfarin

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Cardiovascular Diseases; Clinical Trials as Topic; Female; Fibrinolytic Agents; Humans; Male; Myocardial Infarction; Streptokinase; Warfarin

This study aims to investigate the influence of MEF2A and SLC22A3-LPAL2-LPA polymorphisms on cardiovascular disease susceptibility and responsiveness to warfarin medication in Jordanian patients, during the initiation and maintenance phases of treatment.. Several candidate genes have been reported to be involved in warfarin metabolism and studying such genes may help in finding an accurate way to determine the needed warfarin dose to lower the risk of adverse drug effects, resulting in more safe anticoagulant therapy.. The study population included 212 cardiovascular patients and 213 healthy controls. Genotyping of MEF2A and SLC22A3-LPAL2-LPA polymorphisms was conducted to examine their effects on warfarin efficiency and cardiovascular disease susceptibility using PCR-based methods.. One SNP (SLC22A3-LPAL2-LPA rs10455872) has been associated with cardiovascular disease in the Jordanian population, whereas the other SNPs in the MEF2A gene and SLC22A3-LPAL2-LPA gene cluster did not have any significant differences between cardiovascular patients and healthy individuals. Moreover, SLC22A3-LPAL2-LPA rs10455872 was correlated with moderate warfarin sensitivity, the other SNPs examined in the current study have not shown any significant associations with warfarin sensitivity and responsiveness.. Our data refer to a lack of correlation between the MEF2A polymorphism and the efficacy of warfarin treatment in both phases of treatment, the initiation, and maintenance phases. However, only rs10455872 SNP was associated with sensitivity to warfarin during the initiation phase. Furthermore, rs3125050 has been found to be associated with the international normalized number treatment outcomes in the maintenance phase.

Topics: Anticoagulants; Cardiovascular Diseases; Genetic Predisposition to Disease; Genotype; Humans; Jordan; Lipoprotein(a); MEF2 Transcription Factors; Polymorphism, Single Nucleotide; Warfarin

Trauma teams are often faced with patients on antithrombotic (AT) drugs, which is challenging when bleeding occurs. We sought to compare the effects of different AT medications on head injury severity and hypothesized that AT reversal would not improve mortality in severe traumatic brain injury (TBI) patients.. An Eastern Association for the Surgery of Trauma-sponsored prospective, multicentered, observational study of 15 trauma centers was performed. Patient demographics, injury burden, comorbidities, AT agents, and reversal attempts were collected. Outcomes of interest were head injury severity and in-hospital mortality.. Analysis was performed on 2,793 patients. The majority of patients were on aspirin (acetylsalicylic acid [ASA], 46.1%). Patients on a platelet chemoreceptor blocker (P2Y12) had the highest mean Injury Severity Score (9.1 ± 8.1). Patients taking P2Y12 inhibitors ± ASA, and ASA-warfarin had the highest head Abbreviated Injury Scale (AIS) mean (1.2 ± 1.6). On risk-adjusted analysis, warfarin-ASA was associated with a higher head AIS (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.34-4.42) after controlling for Injury Severity Score, Charlson Comorbidity Index, initial Glasgow Coma Scale score, and initial systolic blood pressure. Among patients with severe TBI (head AIS score, ≥3) on antiplatelet therapy, reversal with desmopressin (DDAVP) and/or platelet transfusion did not improve survival (82.9% reversal vs. 90.4% none, p = 0.30). In severe TBI patients taking Xa inhibitors who received prothrombin complex concentrate, survival was not improved (84.6% reversal vs. 84.6% none, p = 0.68). With risk adjustment as described previously, mortality was not improved with reversal attempts (antiplatelet agents: OR 0.83; 85% CI, 0.12-5.9 [p = 0.85]; Xa inhibitors: OR, 0.76; 95% CI, 0.12-4.64; p = 0.77).. Reversal attempts appear to confer no mortality benefit in severe TBI patients on antiplatelet agents or Xa inhibitors. Combination therapy was associated with severity of head injury among patients taking preinjury AT therapy, with ASA-warfarin possessing the greatest risk.. Prognostic, level II.

Topics: Aged; Anticoagulant Reversal Agents; Aspirin; Brain Injuries, Traumatic; Cardiovascular Diseases; Comorbidity; Deamino Arginine Vasopressin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Hospital Mortality; Humans; Male; Platelet Transfusion; Risk Assessment; Trauma Severity Indices; Treatment Outcome; United States; Warfarin

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide and are significantly associated with multiple comorbid disorders including mental disorders such as psychological distress (PD). At increased risk of PD are CVD patient sub-categories that not only require chronic therapy but also need follow up with continuous blood tests and dose adjustments (like the patients on warfarin). However, not much has been done to ascertain the burden of PD among patients on warfarin in Uganda.. To determine the prevalence and factors associated with PD among patients on anticoagulation with warfarin at the Uganda Heart Institute (UHI).. In this analytical cross-sectional study, 197 participants were sampled from adults on warfarin attending the Uganda Heart Institute (UHI) out patient clinic. The Self Reporting Questionnaire (SRQ-20), a tool with a total maximum score of 20 and cutoff for PD at ≥6 was used to determine the presence of PD among participants, and a socio-demographic questionnaire to document the socio-demographic characteristics of the subjects. Additional questions including the underlying CVD diagnosis, medications used (besides warfarin) and presence of chronic illnesess were also assessed. Bi-variable and multi-variabe logistic regression analysis techniques were used to examine the associations between the dependent and independent variables.. The prevalence of PD was 32%. The unemployed participants were 4.5 times more likely to have PD (adjusted odds ratio [aOR]4.56, 95% confidence interval [CI]: 1.12-18.62, p = 0.04). Participants who had experienced social stressors were more likely to have PD (aOR: 11.38, CI: 3.60-36.04, p < 0.01). Other factors associated with a higher likelihood of having PD included: presence of other chronic comorbidities (aOR: 3.69, CI: 1.24-11.02, p = 0.02) and concomitant use of loop diuretics (aOR: 4.13, CI: 1.67-10.19,p < 0.01). A shorter length of time on warfarin (7-24 months) lowered the likelihood of PD (aOR: 0.23, CI: 0.07-0.74, p = 0.01).. The prevalence of PD was high among patients on warfarin in this low income setting and there is a need to characterize the specific psychiatric disorders in patients with CVD. Interventions that address the high burden of PD are urgently needed in this setting.

Topics: Adult; Cardiovascular Diseases; Cross-Sectional Studies; Hospitals; Humans; Prevalence; Psychological Distress; Uganda; Warfarin

Pharmacogenomic (PGx) testing has proved its utility and cost-effectiveness for some commonly prescribed cardiovascular disease (CVD) medications. In addition, PGx-guided dosing guidelines are now available for multiple CVD drugs, including clopidogrel, warfarin, and statins. The United Arab Emirates (UAE) population is diverse and multiethnic, with over 150 nationalities residing in the country. PGx-testing is not part of the standard of care in most global healthcare settings, including the UAE healthcare system. The first pharmacogenomic implementation clinical study in CVD has been approved recently, but multiple considerations needed evaluation before commencing. The current report appraises the PGx-clinical implementation procedure and the potential benefits of pursuing PGx-implementation initiatives in the UAE with global implications.. Patients prescribed one or more of the following drugs: clopidogrel, atorvastatin, rosuvastatin, and warfarin, were recruited. Genotyping selected genetic variants at genes interacting with the study drugs was performed by real-time PCR.. For the current pilot study, 160 patients were recruited. The genotypes and inferred haplotypes, diplotypes, and predicted phenotypes revealed that 11.9% of the participants were poor CYP2C19 metabolizers, 35% intermediate metabolizers, 28.1% normal metabolizers, and 25% rapid or ultrarapid metabolizers. Notably, 46.9% of our cohort should receive a recommendation to avoid using clopidogrel or consider an alternative medication. Regarding warfarin, only 20% of the participants exhibited reference alleles at VKORC1-1639G > A, CYP2C9*2, and CYP2C9*3, leaving 80% with alternative genotypes at any of the two genes that can be integrated into the warfarin dosing algorithms and can be used whenever the patient receives a warfarin prescription. For statins, 31.5% of patients carried at least one allele at the genotyped SLCO1B1 variant (rs4149056), increasing their risk of developing myopathy. 96% of our cohort received at least one PGx-generated clinical recommendation for the studied drugs.. The current pilot analysis verified the feasibility of PGx-testing and the unforeseen high frequencies of patients currently treated with suboptimal drug regimens, which may potentially benefit from PGx testing.

Topics: Atorvastatin; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Pharmacogenetics; Pilot Projects; Rosuvastatin Calcium; United Arab Emirates; Vitamin K Epoxide Reductases; Warfarin

Atrial fibrillation is a risk factor for dementia, and oral anticoagulant use is associated with a decreased risk of dementia in patients with atrial fibrillation. We aimed to investigate whether the risk of dementia would be different between patients treated with direct oral anticoagulants (DOACs) compared with those with warfarin.. Using the Korean nationwide claims database from January 2014 to December 2017, we identified oral anticoagulant–naive nonvalvular atrial fibrillation patients aged ≥40 years. For the comparisons, warfarin and DOAC groups were balanced using the inverse probability of treatment weighting method. The primary outcome was incident dementia.. Among 72 846 of total study patients, 25 948 were treated with warfarin, and 46 898 were treated with DOAC (17 193 with rivaroxaban, 9882 with dabigatran, 11 992 with apixaban, and 7831 with edoxaban). During mean 1.3±1.1 years of follow-up, crude incidence of dementia was 4.87 per 100 person-years (1.20 per 100 person-years for vascular dementia and 3.30 per 100 person-years for Alzheimer dementia). Compared with warfarin, DOAC showed a comparable risks of dementia, vascular dementia, and Alzheimer dementia. In subgroup analyses, DOAC was associated with a lower risk of dementia than warfarin, particularly in patients aged 65 to 74 years (hazard ratio, 0.815 [95% CI, 0.709–0.936]) and in patients with prior stroke (hazard ratio, 0.891 [95% CI, 0.820–0.968]). When comparing individual DOACs with warfarin, edoxaban was associated with a lower risk of dementia (hazard ratio, 0.830 [95% CI, 0.740–0.931]).. In this large Asian population with atrial fibrillation, DOAC showed a comparable risk of dementia with warfarin overall. DOACs appeared more beneficial than warfarin, in those aged 65 to 74 years or with a history of stroke. For specific DOACs, only edoxaban was associated with a lower risk of dementia than warfarin.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cerebrovascular Disorders; Dementia; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Warfarin

Cardiovascular diseases are among the leading causes of death worldwide. Many of those diseases require treatment with warfarin, an anticoagulant that has a large high inter and intra-variability in the required doses. The aim of this study is to find if there are any associations between rs2108622 of

Topics: Anticoagulants; Apolipoproteins E; Asian People; Cardiovascular Diseases; Case-Control Studies; Cytochrome P-450 CYP2A6; Cytochrome P450 Family 4; Dose-Response Relationship, Drug; Follow-Up Studies; Gene Frequency; Genetic Predisposition to Disease; Healthy Volunteers; Humans; International Normalized Ratio; Jordan; Pharmacogenomic Variants; Warfarin

Topics: Body Mass Index; Cardiovascular Diseases; Fibrinolytic Agents; Humans; Rivaroxaban; Warfarin

While direct oral anticoagulants (DOACs) are considered safe among patients without chronic kidney disease (CKD), the evidence is conflicting as to whether they are also safe in the CKD and end-stage kidney disease (ESKD) population. In this observational cohort study, we examined whether DOACs are a safe alternative to warfarin across CKD stages for a variety of anticoagulation indications.. Individuals on DOACs or warfarin were identified from OptumLabs® Data Warehouse (OLDW), a longitudinal dataset with de-identified administrative claims, from 2010 to 2017. Cox models with sensitivity analyses were used to assess the risk of cardiovascular disease and bleeding outcomes stratified by CKD stage.. Among 351,407 patients on anticoagulation, 45% were on DOACs. CKD stages 3-5 and ESKD patients comprised approximately 12% of the cohort. The most common indications for anticoagulation were atrial fibrillation (AF, 44%) and venous thromboembolism (VTE, 23%). DOACs were associated with a 22% decrease in the risk of cardiovascular outcomes (HR 0.78, 95% CI: 0.77-0.80, p < 0.001) and a 10% decrease in the risk of bleeding outcomes (HR 0.90, 95% CI: 0.88-0.92, p < 0.001) compared to warfarin after adjustment. On stratified analyses, DOACs maintained a superior safety profile across CKD stages. Patients with AF on DOACs had a consistently lower risk of cardiovascular and bleeding events than warfarin-treated patients, while among other indications (VTE, peripheral vascular disease, and arterial embolism), the risk of cardiovascular and bleeding events was the same among DOAC and warfarin users.. DOACs may be a safer alternative to warfarin even among CKD and ESKD patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Insufficiency, Chronic; Severity of Illness Index; United States; Warfarin

Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer.. In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups.. There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50–0.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24–0.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23–0.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56–0.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05).. Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Propensity Score; Retrospective Studies; Stroke; Taiwan; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

Direct oral anticoagulants (DOACs) are replacing warfarin for stroke prevention in patients with atrial fibrillation (AF).. To assess the effectiveness and safety of concomitant treatment with antiplatelet-DOAC compared to antiplatelet-warfarin in patients with acute coronary syndrome (ACS) and AF.. Retrospective propensity score-matched cohort study using United States-based commercial healthcare database from January 2016 to June 2019.. New-users of antiplatelet-DOAC and antiplatelet-warfarin who initiated the combined therapy within 30 days following incident ACS diagnosis.. Primary study outcomes were recurrent cardiovascular diseases (CVD) (ie, a composite of stroke and myocardial infarction) and major bleeding events identified via discharge diagnoses. We controlled for potential confounders via propensity score matching (PSM). We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar time.. After PSM, a total of 2,472 persons were included (1,236 users of antiplatelet-DOAC and 1,236 users of antiplatelet-warfarin). The use of antiplatelet-DOAC (vs. antiplatelet-warfarin) was associated with a reduced rate of recurrent CVD (adjusted HR 0.72, 95% confidence interval [CI], 0.56-0.92) and major bleeding events (adjusted HR, 0.49, 95% CI 0.33-0.72).. Residual confounding.. In real-world data of AF patients with concurrent ACS, the use of antiplatelet-DOAC following ACS diagnosis was associated with a lower rate of recurrent CVD and major bleeding events compared with antiplatelet-warfarin. These findings highlight a potential promising role for DOACs in patients with ACS and AF requiring combined antiplatelet therapy.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Retrospective Studies; United States; Warfarin

Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.

Topics: Animals; Anticoagulants; Blood Coagulation; Cardiovascular Diseases; Cell Line; Cytochrome P-450 Enzyme System; Endothelial Cells; Ginsenosides; Herb-Drug Interactions; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Liver; Panax; Plant Extracts; Rats; Thrombosis; Vascular Cell Adhesion Molecule-1; Warfarin

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Humans; Renal Insufficiency, Chronic; Warfarin

Warfarin is the most widely prescribed oral anticoagulant and is recommended for patients recovering from coronary artery bypass graft (CABG) with atrial fibrillation. Increasing evidence suggested that warfarin increased arterial stiffness in those patients. We aimed to examine the effect of warfarin therapy on aortic stiffness in patients who underwent CABG with or without postoperative warfarin treatment and explored the potential relationships of warfarin therapy with ABCA1 polymorphisms. This was a retrospect observational study of 24 patients who were continuously treated with warfarin were selected as the warfarin group and matched them by age (±3 years) and gender to 48 patients with nonuse of warfarin as the control group. The aortic stiffness, cholesterol efflux capacity, and plasma level of PIVKA-II were measured. Two ABCA1 polymorphisms were genotyped. Compared with baseline, treatment with warfarin for 1 year significantly increased the plasma level of PIVKA-II and aortic stiffness in pulse pressure and pulse wave velocity in patients after CABG. The increase of pulse wave velocity and plasma PIVKA-II level in the TT genotype was significantly greater than the CC genotype when comparing the -565C/T genotypes. The capacity of cholesterol efflux was significantly lower in the TT genotype at baseline and 1-year follow-up than the CC genotype. Postoperative treatment of warfarin for 1 year significantly increased aortic stiffness in patients who underwent CABG. ABCA1 -565C/T polymorphisms affected the cholesterol efflux capacity and were associated with the vitamin K status and the increased aortic stiffness after warfarin treatment in those patients.

Topics: Aged; Anticoagulants; ATP Binding Cassette Transporter 1; Biomarkers; Cardiovascular Diseases; China; Coronary Artery Bypass; Female; Genetic Association Studies; Homozygote; Humans; Male; Middle Aged; Pharmacogenomic Variants; Polymorphism, Genetic; Protein Precursors; Prothrombin; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Stiffness; Warfarin

We compared the risk of bleeding and cardiovascular disease (CVD) events between non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin in people with type 2 diabetes (T2DM).. 862 Incident NOAC users and 626 incident warfarin users with T2DM were identified from within 40 UK general practice (1/4/2017-30/9/2018). Outcomes included incident hospitalisation for bleeding, CVD and re-hospitalisation for CVD within 12 months since first anticoagulant prescription, identified from linked hospitalisation data. A tapered matching method was applied to form comparison cohorts: coarsened exact matching restricted the comparison to areas of sufficient overlap in missingness and characteristics: (i) demographic characteristics; (ii) clinical measurements; (iii) prior bleeding and CVD history; (iv) prescriptions with bleeding; (v) anti-hypertensive treatment(s); (vi) anti-diabetes treatment(s). Entropy balancing sequentially balanced NOAC and warfarin users on their distribution of (i-vi). Weighted logistic regression modelling estimated outcome odds ratios (ORs), using entropy balancing weights from steps i-vi.. The 12-month ORs of bleeding with NOAC (n = 582) vs matched/balanced warfarin (n = 486) were 1.93 (95% confidence interval 0.97-3.84), 2.14 (1.03-4.44), 2.31 (1.10-4.85), 2.42 (1.14-5.14), 2.41 (1.12-5.18), and 2.51 (1.17-5.38) through steps i-vi. ORs for CVD re-hospitalisation was increased with NOAC treatment through steps i-vi: 2.21 (1.04-4.68), 2.13 (1.01-4.52), 2.47 (1.08-5.62), 2.46 (1.02-5.94), 2.51 (1.01-6.20), and 2.66 (1.02-6.94).. Incident NOAC use among T2DM is associated with increased risk of bleeding hospitalisation and CVD re-hospitalisation compared with incident warfarin use. For T2DM, caution is required in prescribing NOACs as first anticoagulant treatment. Further large-scale replication studies in external datasets are warranted.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Comorbidity; Cytarabine; Diabetes Mellitus, Type 2; England; Female; Hemorrhage; Humans; Incidence; Male; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Blood Pressure; Cardiovascular Diseases; Dabigatran; Humans; Thrombin; Warfarin

To investigate the frequency and degree of azole antifungal agents that influence the anticoagulant activity of warfarin to reduce the potential bleeding risk and provide a reference for rational administration of warfarin in clinics.Patients with an abnormal international normalized ratio (INR; INR ≥ 4.5) and treated with warfarin plus azole antifungal agents were screened from February 2011 to July 2016, and their data were extracted.Thirty-two patients treated with warfarin plus azole antifungal agents were included. The INR of all the included patients increased by more than 20% of the INR of warfarin alone, and the warfarin sensitivity index showed an upward trend. The INRs of 21 patients treated with fluconazole (FLCZ) and warfarin was closely monitored for 1 week after the combination treatment, and the interaction between warfarin and the azole antifungal agents peaked on the seventh day. The INRs when warfarin was coadministered with azoles (Y) correlated significantly with those in the absence of azoles (X): FLCZ: Y = 1.2515X + 2.1538, R = 0.8128; and voriconazole Y = 2.4144 X + 2.6216, R2 = 0.7828.The combination of FLCZ and voriconazole will enhance the anticoagulant effect of warfarin. Therefore, it is recommended to detect the genotype of CYP2C9 in patients and evaluate the interaction between the 2 drugs to adjust the warfarin dose. It is also recommended to closely monitor INR within 1 week of the addition of azole antifungal agents.

Topics: Adult; Aged; Anticoagulants; Antifungal Agents; Azoles; Cardiovascular Diseases; Cytochrome P-450 CYP2C9; Drug Resistance; Drug Therapy, Combination; Female; Genotype; Humans; International Normalized Ratio; Male; Metabolism, Inborn Errors; Middle Aged; Retrospective Studies; Treatment Outcome; Warfarin

Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) VS warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban-warfarin, 18,131 dabigatran-warfarin, and 55,359 rivaroxaban-warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59-0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73-0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72-1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57-0.67; NCO: HR: 0.64; 95% CI 0.60-0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71-0.89; NCO: HR: 0.84; 95% CI 0.76-0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02-1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99-1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiovascular Diseases; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Medicare; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

To assess the effectiveness and safety of rivaroxaban versus warfarin for the prevention of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with type 2 diabetes (T2D) and non-valvular atrial fibrillation (NVAF).. Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant-naïve patients with NVAF and comorbid T2D and ≥12 months of insurance coverage prior to rivaroxaban or warfarin initiation. Differences in baseline covariates between cohorts were adjusted for using inverse probability of treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a MACE, MALE or major bleeding event, oral anticoagulant discontinuation/switch, insurance disenrolment or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression.. We identified 10 700 rivaroxaban users (24.1% received a reduced dose) and 13 946 warfarin users. The median (25%, 75% range) age was 70 (62, 79) years, CHA2DS2-VASc score was 4 (3, 5) and duration of available follow-up was 1.4 (0.6, 2.7) years. Eleven percent of patients had peripheral artery disease, 5.1% had coronary artery disease, and 5.1% had a prior MALE, at baseline. Rivaroxaban was associated with a 25% (95% CI 4-41) reduced risk of MACE and a 63% (95% CI 35-79) reduced risk of MALE compared to warfarin. Major bleeding risk did not significantly differ between cohorts (HR 0.95).. Among patients with NVAF and T2D treated in routine practice, rivaroxaban was associated with lower risks of both MACE and MALE versus warfarin, with no significant difference in major bleeding.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Peripheral Arterial Disease; Propensity Score; Retrospective Studies; Rivaroxaban; Treatment Outcome; Warfarin; Young Adult

Treatment patterns and outcomes of individuals with vascular disease who have new-onset atrial fibrillation (AF) are not well characterized.. Among patients with new-onset AF, we analyzed treatment and outcomes in those with or without vascular disease in the ORBIT-AF II registry. Vascular disease was defined as coronary disease with or without myocardial infarction (MI) or revascularization, or peripheral artery disease. The primary outcomes included major adverse cardiovascular or neurological events (MACNE) and major bleeding. Cox proportional hazard models were used to adjust the difference in patient characteristics.. Overall 1920 of 6203 (31.0%) of new-onset AF had vascular disease. In patients with vascular disease, 62.2% of those were treated with direct oral anticoagulants (DOACs) and 23.4% with warfarin. Dual therapy and triple therapy were used in 36.9% and 4.9%, respectively. Vascular disease patients had increased risk of MACNE (adjusted hazard ratio [aHR] 1.83 [95%CIs 1.32-2.55]), but not major bleeding (aHR 1.24 [0.95-1.63]). Among patients with vascular disease, relative to those on warfarin, those treated with DOACs had similar risk for MACNE (aHR 1.20 [0.77-1.87]) but lower risks for bleeding, although it did not reach statistical significance (aHR 0.70 [0.43-1.15]). Concomitant antiplatelet therapy was associated with higher bleeding (aHR 2.27 [1.38-3.73]) with no apparent reduction in MACNE (aHR 1.50 [1.00-2.25]).. Most patients with AF and vascular disease were managed with oral anticoagulation. About half of them were also treated with concomitant antiplatelet therapy, which was associated with increased risk of bleeding, without evidence of improved cardiovascular outcomes.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

The development of non-vitamin K-dependent oral anticoagulants (NOACs) is a new alternative to treatment with warfarin. The purpose of this study was to explore drug prescription decisions of NOACs or warfarin from hospital physicians in cardiovascular departments.. A qualitative study with focus group interviews was conducted in three different hospitals. The interview guide explored the background of prescribing anticoagulants (warfarin, dabigatran, rivaroxaban, and apixaban) and experiences with effect and side-effects they had observed in patients.. The systematic text condensation eluded four main themes: when to prescribe NOACs, concern about side-effects, pharmaceutical properties and patient adherence, and prescribing policy and intra-professional communication. All available anticoagulants were prescribed. However, no specific NOAC was preferred. Factors perceived as contraindications for NOACs varied among the doctors. Most had observed side-effects of NOACs; however, these rarely influenced prescribing decisions due to small differences in safety profiles. Few drug-drug interactions and fixed daily doses made NOACs easy to prescribe; but some doctors had experienced lack of drug effect for some patients. Non-adherence with NOACs was harder to spot. Some different prescribing cultures had evolved between the different hospitals and between general practitioners.. The hospital physicians chose anticoagulants based on patient conditions as renal function, bleeding risks, and drug interactions being the most common taken into account. They could not say which NOAC was best, and wish that future studies could compare the different NOACs, and not just compare with warfarin.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Cardiovascular Diseases; Clinical Decision-Making; Dabigatran; Drug Monitoring; Drug Resistance; Factor Xa Inhibitors; Focus Groups; General Practitioners; Hemorrhage; Humans; Medical Staff, Hospital; Medication Adherence; Norway; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Qualitative Research; Risk; Rivaroxaban; Warfarin

Background Although it can result in serious complications due to its narrow therapeutic index, warfarin is widely used in the treatment and prevention of thromboembolic disorders. However, patients' adherence and knowledge are determinants of therapeutic success. Objective We sought to validate instruments to provide a reliable means of identifying gaps in patient understanding and nonadherence to inform targeted pharmacists' interventions to improve these measures. Methods A cross-sectional survey was conducted. Patients' knowledge about warfarin was rated using an Arabic-language tool. Medication adherence was assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8). The international normalized ratio (INR) control was quantified by the Rosendaal Method. Setting At the Security Forces hospital anticoagulant clinic (ACC), Riyadh. Main outcome measure Validity of a Knowledge and adherence tool. Results Totally, 101 patients completed the questionnaires. Interestingly, the knowledge tool demonstrated good internal consistency (total Cronbach's alpha = 0.75) and significant concurrent validity with adherence levels. Fifty-two patients were classified as having unsatisfactory knowledge. Deficiency in knowledge was most obvious with respect to the consequences of missing a dose and when to seek immediate medical attention. The MMAS-8 had moderate reliability (Cronbach's alpha = 0.65); however, its concurrent validity with good INR control was not demonstrated. Conclusions This study revealed high prevalence of nonadherence and poor knowledge in the population visiting the ACC. Given that available knowledge and adherence tools seemed to have little validity in predicting clinical outcomes, structured tools should be designed, considering progression in clinical outcomes with future pharmacists' interventions.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Female; Hospitals, Military; Humans; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Pharmacy Service, Hospital; Reproducibility of Results; Saudi Arabia; Self Report; Warfarin

Topics: Biomarkers, Pharmacological; C-Reactive Protein; Cardiovascular Diseases; Cytochrome P-450 CYP2C19; Humans; Myocardial Infarction; Precision Medicine; Vitamin K Epoxide Reductases; Warfarin

Topics: Aged; Anticoagulants; Antihypertensive Agents; Bimatoprost; Cardiovascular Diseases; Cataract; Cataract Extraction; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Timolol; Trabeculectomy; Visual Acuity; Visual Field Tests; Visual Fields; Warfarin

The management of atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs), but data on their clinical effectiveness and safety outside clinical trial settings are limited.. The RAFFINE registry is an observational, multicenter, prospective registry of Japanese patients with AF, designed to follow clinical events over 3 years. Patient enrollment was conducted from 2013 to 2015 at university hospitals, general hospitals, and private clinics to ensure inclusion of a broad spectrum of representative AF patients. The primary outcome events in this study will be ischemic stroke, systemic embolism, and major bleeding.. We enrolled 3901 ambulatory patients with AF from 4 university hospitals and 50 general hospitals/clinics in Japan. The mean patient age was 72.6 years and 68.5% were male. The type of AF was paroxysmal in 37.8%, persistent in 9.3%, and permanent in 51.7%. Major coexisting diseases were hypertension (72.7%), diabetes mellitus (30.3%), congestive heart failure (23.8%), history of ischemic stroke or transient ischemic attack (15.1%), and coronary artery disease (13.7%). Of the entire cohort, 44.6% were treated with warfarin and 43.0% were treated with DOACs. The prescription of DOACs exceeded that of warfarin in the general hospitals and clinics. Risk scores such as CHADS. The RAFFINE registry at baseline described the current status of anticoagulation therapy in Japan and long-term follow-up data will identify how outcomes vary between stratified groups in patients with AF in the DOAC era (UMIN Clinical Trials Registry UMIN000009617).

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Diabetes Complications; Embolism; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Prospective Studies; Registries; Research Design; Risk Factors; Treatment Outcome; Warfarin

The pharmacokinetics and pharmacodynamics of warfarin remained unaffected by tolvaptan during clinical trials. However, tolvaptan prolonged the prothrombin time-international normalized ratio (PT-INR) level of patients with cardiovascular disease taking warfarin. Tolvaptan was prescribed to 576 patients from December 2010 to December 2015. Of these patients, 37 underwent anticoagulant therapy. We investigated PT-INR fluctuation immediately before tolvaptan therapy was initiated. PT-INR remained unchanged in the control group and in groups administered with less than 7.5 mg/d tolvaptan, whereas it was significantly increased (p=0.03) in the group administered with more than 7.5 mg/d tolvaptan. This result indicates the possibility that tolvaptan affects the pharmacodynamics of warfarin in vivo. However, further research is necessary to clarify the mechanism of this phenomenon.

Topics: Administration, Oral; Anticoagulants; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cardiovascular Diseases; Drug Interactions; Drug Therapy, Combination; Female; Humans; International Normalized Ratio; Male; Prothrombin Time; Retrospective Studies; Tolvaptan; 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

Advances in cancer therapy have led to a significant improvement of survival in most types of malignancies over the past few decades. As a result, there is a growing population of cancer survivors, expected to reach 18 million people in 2030 in the US and a similar number in Europe. Interestingly, cancer survivor studies have shown that although about half of these patients eventually die of cancer, one third of them actually die of cardiovascular disease. Arrhythmias represent a significant part of cardiovascular complications and atrial fibrillation is the main arrhythmia occurring in cancer patients.Antithrombotic therapy is a challenge: the optimal international normalized ratio (INR) level in patients on therapy with vitamin K antagonists is achieved in only 12% of them; in these patients, direct oral anticoagulants seem to be effective and safe for the prevention of stroke and systemic embolic events compared to warfarin and have similar risk of major bleeding. Among the trials, ENGAGE AF-TIMI 48 provides more data on the efficacy and safety of edoxaban in cancer patients.

Topics: Anticoagulants; Atrial Fibrillation; Cancer Survivors; Cardiovascular Diseases; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; International Normalized Ratio; Neoplasms; Pyridines; Stroke; Thiazoles; Warfarin

Topics: Adrenomedullin; Adult; Aged; Ankle Brachial Index; Anticoagulants; Asymptomatic Diseases; Atrial Fibrillation; Atrial Natriuretic Factor; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Female; Fibrinogen; Germany; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenprocoumon; Protein Precursors; Pulmonary Embolism; Risk Factors; Stroke; Stroke Volume; Vascular Stiffness; Venous Thrombosis; Warfarin

Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, p<0.01). Twenty-eight patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or dose reduction of warfarin after coadministration of tramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Prothrombin Time; Risk Factors; Serum Albumin; Tramadol; Warfarin

Calcific uremic arteriolopathy (CUA) is an often-fatal condition in dialysis patients. The clinical descriptions and treatments of CUA patients have been confined mostly to case reports. We report a comprehensive characterization of CUA and its associated diagnosis, treatment patterns, and outcome.. An internet-based registry collected information about CUA in dialysis patients. Univariate analysis using Cox proportional hazards models estimated hazard ratios of the association between clinical characteristics, laboratory values, and treatments with all-cause mortality.. A total of 117 CUA patients had adequate information for analysis. The majority of patients (56.7%) were diagnosed clinically, with only 32.5% biopsied. Debridement was undertaken in 42.6% of cases. Intravenous sodium thiosulfate (STS) was initiated in 54.7% of patients; most received ≥ 12.5 g of STS (98.3%) for < 3 months (79.7%). Mean parathyroid hormone (PTH) and phosphorus (P) were 459 ± 492 pg/mL and 6.3 ± 2.1 mg/dL, respectively. A total of 24 patients (21.6%, of 111 with information) died, with a median survival time of 2.9 months. In univariate analysis, higher mortality was observed in patients with cardiovascular disease (CVD; HR = 10.47; 95% CI 1.40-78.38), those taking warfarin at time of diagnosis (HR = 2.74; 95% CI 1.16-6.51), and those who had both diabetes (DM) and CVD and who were taking warfarin (HR = 13.41; 95% CI 1.66-109.29).. In real-world clinical practice, there is substantial variability in the diagnosis and treatment of CUA. There is usually only modest derangement of bone and mineral parameters at the time of diagnosis. Death is common. The presence of CVD and use of warfarin may influence clinical outcome after diagnosis of CUA.

Topics: Aged; Anticoagulants; Arterioles; Calciphylaxis; Cardiovascular Diseases; Chelating Agents; Debridement; Diabetes Mellitus; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Registries; Renal Dialysis; Risk Factors; Survival Rate; Thiosulfates; Warfarin

Although warfarin remains important despite the widespread use of nonvitamin K antagonist oral anticoagulants (NOACs), to date, the reality of warfarin use in the "NOACs era" is unclear. This multicenter observational study aimed to clarify the key factors contributing to warfarin treatment stability.. The practical use of warfarin, stability of warfarin therapy, and factors contributing to this stability were investigated in community-based hospitals through a real-world study. Clinical data were retrospectively extracted from the medical records of warfarin-treated Japanese patients (age, 71.3±5.5 years) with atrial fibrillation (AF), prosthetic heart valve, or other concerns requiring anticoagulation. Treatment stability was considered as time in therapeutic range of international normalized ratio of prothrombin time (TTR: %). The factors contributing to TTR were investigated, including CHADS. Mean CHADS. This retrospective study demonstrated that the CHADS

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Blood Coagulation; Cardiovascular Diseases; Echocardiography; Female; Hepatorenal Syndrome; Humans; Kidney Function Tests; Liver Function Tests; Magnetic Resonance Imaging; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Warfarin

To explore the effectiveness of a patient education programme for chronic disease self-management in terms of whether (a) patients are taught to perform the medical procedure and (b) nurses have evidence of patients' proficiency when they start self-management.. Patients were followed through an education programme for oral anticoagulation therapy, involving the use of INR-monitors. Training sessions were video-recorded and analyzed using Conversation Analysis. 55 instructional opportunities were identified, and the relationship between instructional response and patients' subsequent (un)successful demonstration of the procedure traced.. Patient errors provide the most frequent type of instructional opportunity, but not all are addressed; a significant number is allowed to pass uncorrected. Consequently, patients are not given the opportunity to learn. In the majority of cases where instructional opportunities are missed, patients subsequently do not demonstrate a correct understanding of the procedure.. Patients are allowed to start self-management although nurses do not have evidence that they are capable of performing all aspects of the medical procedure correctly.. Effective practice suggests that nurses take measures to minimize the amount of missed instructional opportunities that arise and ensure that errors are pursued until patients demonstrate proficiency in all aspects of the procedure.

Topics: Administration, Oral; Adult; Anticoagulants; Cardiovascular Diseases; Denmark; Female; Health Knowledge, Attitudes, Practice; Humans; International Normalized Ratio; Male; Middle Aged; Patient Education as Topic; Program Evaluation; Self Care; Self-Management; Warfarin

Ischemic stroke is a risk associated with atrial fibrillation (AF) and is estimated to occur five times more often in afflicted patients than in those without AF. Anti-thrombotic therapy is recommended for the prevention of ischemic stroke. Risk stratification tools, such as the CHADS. Bivariate and multivariate data analysis strategies were used to analyze 2010 National Ambulatory Care Survey (NAMCS) data. NAMCS is designed to collect data on the use and provision of ambulatory care services nationwide. The study population for this research was US adults with a diagnosis of AF. Warfarin prescription was the dependent variable for this study. The study population was 7,669,844 AF patients.. Bivariate analysis revealed that of those AF patients with a high CHADS. Overall, warfarin appears to be under-prescribed for patients with AF regardless of the risk stratification system used. Based on the key findings of our study opportunities for interventions are present to improve guideline adherence in alignment with risk stratification for stroke prevention. Interprofessional health care teams can provide improved medical management of stroke prevention for patients with AF. These interprofessional health care teams should be constituted of primary care providers (physicians, physician assistants, and nurse practitioners), nurses (RN, LPN), and pharmacists (PharmD, RPh).

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Guideline Adherence; Humans; Male; Middle Aged; Multivariate Analysis; North America; Risk Assessment; Risk Factors; Stroke; Warfarin

Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear.. We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups.. In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Embolism; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Proportional Hazards Models; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Time Factors; 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

Atrial fibrillation (AF) affects an estimated 1.5 million individuals in Japan, increasing their stroke risk and imposing considerable costs on the Japanese healthcare system. To reduce stroke incidence, guidelines recommend using anticoagulants in moderate-to-high risk non-valvular AF (NVAF) patients; however, many patients receive no treatment, aspirin only, or remain poorly-controlled on vitamin K antagonists (VKAs) due to high VKA discontinuation rates and non-adherence to guidelines. A prevalence-based Markov model was developed to estimate the clinical and budgetary impact of treating these patients with Xarelto(TM) (rivaroxaban, Bayer AG) in Japan.. Population, baseline risk of events, and associated management costs were estimated using data from Japanese publications where available. Treatment efficacy and safety were derived from published data and the J-ROCKET AF trial. Drug and physician visit costs were based on data from the Ministry of Health, Labor, and Welfare, the J-ROCKET AF trial, and Japanese clinical guidelines.. This model demonstrates that increased use of rivaroxaban in inadequately-managed NVAF patients could avoid 456 081 non-fatal ischemic strokes (IS) and 76 975 cardiovascular deaths over 10 years in Japan. This clinical benefit offsets the increased incidence of myocardial infarctions and anticoagulant-related bleeding. Decreased event costs could lead to a ¥188.4 billion decrease in net spending over the analysis time horizon.. Introducing rivaroxaban may decrease the burden of NVAF in Japanese society. From a clinical perspective, the reduction in IS and embolic events outweighs the increased risk of anticoagulant-related bleeding; from an economic perspective, reduced event costs offset drug and physician visit costs, resulting in cost savings.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cardiovascular Diseases; Female; Humans; Japan; Male; Markov Chains; Middle Aged; Models, Econometric; Practice Guidelines as Topic; Rivaroxaban; Stroke; Warfarin

Previous studies have shown that homocysteine and folate levels in plasma are associated with risk for cardiovascular events and mortality. The aim of this study was to investigate if plasma concentrations of total homocysteine and folate can predict major bleeding, cardiovascular events, and all-cause mortality in patients being treated with warfarin.. In a longitudinal cohort study, 719 patients who were taking warfarin were followed for 3001 treatment years. The following were recorded and classified: major bleeding; cardiovascular events including stroke, arterial emboli, and myocardial infarction (MI); and mortality. Blood samples collected at baseline were analysed for plasma homocysteine and folate levels.. After adjustment for age, C-reactive protein, and creatinine, high homocysteine levels were associated with cardiovascular events [hazard ratio (HR) 1.23 per standard deviation (SD); 95% confidence interval (CI): 1.03-1.47], MI (HR 1.38 per SD; 95% CI: 1.03-1.85), and all-cause mortality (HR 1.41 per SD; 95% CI: 1.19-1.68). The highest tertile of folate compared to the lowest tertile was associated with decreased risk for both cardiovascular events (HR 0.64; 95% CI: 0.43-0.91) and MI (HR 0.45; 95% CI: 0.21-0.97). There was no association between major bleeding and homocysteine or folate levels.. In patients receiving warfarin treatment, high homocysteine and low folate plasma concentrations are associated with increased risk for cardiovascular events but not major bleeding. For homocysteine levels, there is also an association with all-cause mortality.

Topics: Aged; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Male; Warfarin

In heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments.. In the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF≤35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5±1.8 years. Although no differences between treatments were observed on primary outcome (death, stroke, or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups.. Baseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and cardiovascular death), and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF of <15% (incidence rates: 2.04 versus 0.95/100 patient-years; P=0.009), which more than doubled the adjusted stroke risk (adjusted hazard ratio, 2.125; 95% CI, 1.182-3.818; P=0.012). In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1.346; 95% CI, 1.044-1.737; P=0.022; P value for interaction=0.04).. In patients with systolic HF and sinus rhythm, LVEF is inversely associated with death and its components, whereas an association with stroke exists for very low LVEF values. An interaction with warfarin treatment on stroke risk may exist.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Topics: Aged; Aspirin; Cardiovascular Diseases; Cerebral Hemorrhage; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Risk Factors; Stroke; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Warfarin

The aim of this single-cohort prospective study was to evaluate the risk of adverse outcomes after tooth extraction in patients suffering from cardiovascular disorders and under oral anticoagulant therapy with an international normalized ratio within the value of 3.0.. Two hundred ninety-three patients (mean age of 58.7 years) were enrolled and 560 tooth extractions were performed. Fresh extraction sockets were treated with collagen tablets and sutures. The risk of increased bleeding rate was evaluated for type of drug therapy (acenocoumarol or warfarin), type of cardiovascular diseases, and number of tooth extractions. Level of significance was set at 0.05.. The overall bleeding event rate was 6.8%. Among patients who had bleeding events, 4 suffered from valvular disorders, whereas 11 suffered from arrhythmias (8) or cardiomyopathies (3). The remaining 5 patients had a history of cardiomyopathy and arrhythmia.The bleeding events in patients who had more than 2 tooth extractions were significantly higher than those observed in patients who had only 1 tooth extraction (P <0.05).. Patients who received more than 2 tooth extractions, who were under treatment with acenocoumarol, and who suffered from multiple cardiovascular diseases were at high risk for bleeding events.

Topics: Adult; Aged; Anticoagulants; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Poland; Postoperative Hemorrhage; Prospective Studies; Sutures; Tooth Extraction; 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

To critically appraise the evidence on dabigatran etexilate, Pradaxa, as an alternative to warfarin for stroke prevention among patients with nonvalvular atrial fibrillation. This information can assist nurse practitioners in making informed treatment decisions.. A review of the literature was conducted using CINAHL and PubMed databases. Reports published on cardiovascular organizational web sites were also searched, along with reference lists of relevant published articles and reports.. Significant evidence from the PETRO and RE-LY trials and postmarketing analyses of dabigatran etexilate indicate that this direct thrombin inhibitor is as efficacious as warfarin in ischemic stroke prevention. In fact, the studies found that patients taking dabigatran etexilate had fewer incidences of ischemic stroke and intracranial hemorrhage than those taking warfarin. Risk for major gastrointestinal bleeding appears to be higher than that for warfarin.. Patients taking dabigatran etexilate do not require blood work to assess international normalized ratio (INR) levels. Because this drug is excreted primarily by the kidneys, reassessment of renal function is critical during treatment, especially with concomitant use of diuretics, fluctuating renal function, or hypovolemia. As with warfarin, nurse practitioners should educate patients about when to seek immediate care for the development of anticoagulant-associated bleeding.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiovascular Diseases; Dabigatran; Hemorrhage; Humans; Stroke; Warfarin

Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia, and is associated with an increased risk of death, stroke, and other thromboembolic events. Valvular heart disease (VHD) frequently coexists with AF, mostly in elderly patients. After the introduction of novel oral anticoagulants (NOACs) approved for the prevention of stroke in non-valvular atrial fibrillation (NVAF) on the basis of recent trials, the importance of a universal definition of NVAF was raised in clinical practice. In the most recent guidelines, the term valvular AF is used to imply that AF is related to rheumatic valvular disease (predominantly mitral stenosis), or prosthetic heart valves. In all the trials comparing NOACs and warfarin, a significant percentage of patients presented any type of VHD, excluding rheumatic mitral stenosis and mechanical heart valve. The subgroups analysis performed, so far showed no significant differences in terms of efficacy in the VHD subgroup compared to the general AF population. A restrictive definition of valvular AF (i.e., rheumatic mitral stenosis and mechanical heart valve) seems to be the most appropriate to contraindicate treatment with NOACs for AF thromboprophylaxis. In the remaining AF patients with significant valvular disease who per se would not require oral anticoagulation, NOACs should be allowed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Heart Valve Diseases; Humans; Thromboembolism; Warfarin

In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin.. This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases.. Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA₂DS₂-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS₂ score or ≥3 points of other components of CHA₂DS₂-VASc score was a significant predictor for development of ischemic stroke.. NVAF patients with high CHADS₂/CHA₂DS₂-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Case-Control Studies; Cerebral Infarction; Female; Humans; Male; Middle Aged; Multivariate Analysis; Risk Factors; Stroke; Warfarin

Topics: Aged; Angiotensin Amide; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Endothelium, Vascular; Female; Glomerular Filtration Rate; Humans; Inflammation; Kidney; Male; Middle Aged; Risk Factors; Severity of Illness Index; Smoking; Treatment Outcome; von Willebrand Factor; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Humans; Risk Factors; Stroke; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are broadly preferable to vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (AF) given their overall net clinical benefit. We report an audit of the profile of OAC usage and adverse events in patients attending a specialist AF clinic.. Patients attending our specialist AF clinic who were commenced on NOACs for SPAF between January 2013 and August 2014 were included and electronic medical records were retrospectively reviewed between August 2014 and November 2014, to collect demographic, clinical and outcome data. Outcomes included cerebrovascular and bleeding events, death, switching between NOACs or to VKA, dose changes, cessation of NOACs and the reasons for these. To provide perspective, descriptive comparisons were made with a historical cohort of warfarin users attending the specialist AF clinic prior to the introduction of NOACs.. We report data on 813 patients as follows: (i) 233 consecutive patients (mean (standard deviation) age 74 (10) years, 45.1% female) initiated on NOACs, with median (interquartile range) CHA2 DS2 -VASc score 3 (2-5) and HAS-BLED score 1 (1-2); and (ii) a historical cohort of 580 patients on warfarin (mean (SD) age 75 (10) years, 42.1% female) with broadly similar demographics. Overall, 54.5% (127/233) were started on rivaroxaban, 22.7% (53/233) on dabigatran and 22.7% on apixaban. Two patients experienced a transient ischaemic attack; 31 patients (13%) contributed to 37 documented bleeding events of which five bleeds (in four patients, 1.7%) were classified as major. There were seven deaths; cause of death was not available for three and the others were not related to NOACs. Eighteen (7.7%) patients switched NOACs, 2 (0.9%) patients switched to warfarin and 8 (3.4%) had their NOACs stopped. There were no ischaemic strokes in the NOAC cohort, compared with nine in the warfarin cohort, with a similar rate of major bleeding (1.7% for NOACs and 1.6% for warfarin). There were more gastrointestinal haemorrhages in the NOAC cohort (3.4% vs. 0.7% with warfarin).. In this specialist AF clinic, patients prescribed NOACs had a favourable adverse event profile with good efficacy for stroke prevention, with a low rate of cessation or switch to warfarin.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Clinical Audit; Dabigatran; Drug Substitution; Female; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Warfarin

Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients.. We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death.. Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE.. TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Myocardial Infarction; Patient Outcome Assessment; Proportional Hazards Models; Prospective Studies; Regression Analysis; Stroke; Vitamin K; Warfarin

The prevalence of atrial fibrillation increases with age, but age-specific data on the incidence of stroke and death in anticoagulated patients with atrial fibrillation are more limited, particularly with regard to comparisons of relative risks of clinical outcomes between the different age strata in relation to quality of anticoagulation control among warfarin users.. We investigated the incidence of adverse outcomes between tertiles of age groups (age, <67 [n=722]; age, 67-74 [n=747]; and age, ≥75 [n=824]) in 2293 patients with atrial fibrillation participating in warfarin arm in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. The average time in therapeutic range was calculated as a measure of anticoagulation control and related to clinical outcomes.. Absolute rates for stroke/systemic embolism (SSE), cardiovascular death, or any clinically relevant bleeding increased with increasing age strata. The combined end point of cardiovascular death and SSE was the highest in the top tertile (adjusted hazard ratio, 2.63; 95% confidence interval, 1.23-5.63) compared with the middle and lowest tertiles (P for trend=0.01). For bleeding, there was no significant difference in relative risks between the age strata (P for trend=0.55 in the warfarin group and in the warfarin group with time in therapeutic range≥60%, P for trend=0.60). The quality of anticoagulation control (time in therapeutic range) significantly correlated with any clinically relevant bleeding (r=-0.91; P<0.001) and cardiovascular death/SSE rates (r=-0.76; P=0.01).. Elderly patients with atrial fibrillation have higher absolute risks of cardiovascular death, SSE, and bleeding, but relative risks of clinically relevant bleeding are not significantly different with increasing age strata. A significant inverse relationship between time in therapeutic range and bleeding and cardiovascular death/SSE emphasizes the importance of good quality anticoagulation control.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cohort Studies; Embolism; Female; Hemorrhage; Humans; Intracranial Embolism; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Stroke; Warfarin

To evaluate the prevalence of dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia.. Department of Ophthalmology, Ludwig-Maximilans Universität, München, Germany.. Retrospective study.. Two groups of patients were screened retrospectively over a 5-year period for the inclusion criterion of severe retrobulbar hematoma after retrobulbar or parabulbar injection. The first group consisted of emergency cases referred to the clinic. A second group of patients had received retrobulbar block at the hospital. All cases were collected and screened for the presence of antiplatelet therapy.. Among roughly 160 000 patient records screened, 3 patients with grade IV retrobulbar hematoma were identified. Two of these patients were taking dual antiplatelet medications and 2 were on anticoagulation therapy during the time of retrobulbar or peribulbar anesthesia. None of the cases showed single medication platelet inhibition. The visual acuity of all patients stayed low at the 6-month follow-up (1.2 logMAR in 1 patient and no light perception in 2 patients).. Retrobulbar hematoma is a rare but severe complication of retrobulbar anesthesia. With the high prevalence of dual platelet inhibition found in these cases, a prospective controlled trial seems unethical. In these high-risk patients, surgery should be performed under topical anesthesia if possible or general anesthesia if necessary.. No author has a financial or proprietary interest in any material or method mentioned.

Topics: Aged; Anesthesia, Local; Anticoagulants; Arterial Occlusive Diseases; Aspirin; Cardiac Surgical Procedures; Cardiovascular Diseases; Clopidogrel; Drug Combinations; Female; Humans; Lens Implantation, Intraocular; Male; Phacoemulsification; Platelet Aggregation Inhibitors; Retrobulbar Hemorrhage; Retrospective Studies; Risk Factors; Ticlopidine; Warfarin

Although atrial fibrillation (AF) occurs frequently in patients hospitalized with acute coronary syndrome (ACS), strategies for prevention of thromboembolic complications are poorly characterized.. We sought to examine exposure to warfarin and P2Y12 inhibitors and clinical outcomes among patients with AF and ACS.. Patients age >65 years hospitalized with a primary diagnosis of ACS and a secondary diagnosis of AF between 2007 and 2010 were identified in the Medicare 5% sample. Medication exposure was ascertained during a 90-day period following the index discharge using Medicare drug claims. Among patients who were alive and not readmitted during the ascertainment period, we examined the cumulative incidence of all-cause mortality and all-cause readmission by medication exposure at 1 year.. A total of 2509 Medicare beneficiaries met the inclusion criteria. Among the 1633 patients (65%) who were alive and not readmitted during the 90-day ascertainment period, 24.0% received warfarin, 38.9% received P2Y12 inhibitors, 10.2% received combination therapy, and 26.8% received neither therapy. Readmission rates were high in all groups at 1 year (warfarin, 47.5%; P2Y12 inhibitors, 46.6%; combination therapy, 38.0%; and neither therapy, 39.3%), and the overall 1-year mortality rate was 12.5%.. Among Medicare beneficiaries with AF and ACS, combination therapy with warfarin and P2Y12 inhibitor was uncommon during the 90-day ascertainment period, and more than one-quarter of patients had no claims for warfarin or P2Y12 inhibitors. Rates of all-cause readmission and mortality within 1 year of hospitalization for ACS were high.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cellulitis; Comorbidity; Drug Therapy, Combination; Drug Utilization; Female; Gastrointestinal Diseases; Humans; Male; Medicare; Myocardial Revascularization; Patient Readmission; Pulmonary Disease, Chronic Obstructive; Purinergic P2Y Receptor Antagonists; Stents; Thromboembolism; United States; Warfarin

Atrial fibrillation (AF) is the most common cardiac rhythm disorder with a significant health burden. The aim of this study was to characterise patients with recently diagnosed AF and to estimate the rates of comorbidities and outcome events requiring hospitalisation in routine clinical practice.. Pharmacoepidemiological cohort study using observational data.. This study included 16 513 patients with a first diagnosis of AF between 1 January 2005 and 28 February 2010 (newly diagnosed patients) using data from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and the Office for National Statistics mortality data. Exposure was stratified by vitamin K antagonist (VKA) exposure (non-use, current, recent and past exposure) based on prescriptions and/or international normalised ratio measurements, and followed for outcome events of interest based on diagnosis codes in the databases, that is, vascular outcomes, bleeding events and others. The main focus of the study was on outcome events requiring hospitalisation using the HES data.. The incidence of vascular outcome hospitalisations (myocardial infarction (MI), stroke or systemic arterial peripheral embolism) was 3.8 (95% CI 3.5 to 4.0)/100 patient-years. The incidence of stroke was 0.9 (0.8 to 1.1) during current VKA exposure, 2.2 (1.6 to 2.9) for recent, 2.4 (1.9 to 2.9) for past and 3.4 (3.1 to 3.7) during non-use. MI incidence was 0.7 (0.6 to 0.9) for current VKA exposure, 0.7 (0.4 to 1.2) for recent, 1.1 (0.8 to 1.5) for past and 1.9 (1.7 to 2.1) during non-use. The incidence of bleeding event hospitalisations was 3.8 (3.4 to 4.2) for current VKA exposure, 4.5 (3.7 to 5.5) for recent, 2.7 (2.2 to 3.3) for past and 2.9 (2.6 to 3.2) during non-use; 38% of intracranial bleeds and 6% of gastrointestinal bleeds were fatal.. This population-based study from recent years provides a comprehensive characterisation of newly diagnosed patients with AF and incidence estimates of common outcomes with a focus on hospitalised events stratified by VKA exposure. This study will help to place future data on new oral anticoagulants into perspective.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Thrombosis; Warfarin; Young Adult

Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation.. To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation.. Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24,317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR).. (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date.. A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m2 [eGFR<60]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR>30-60: event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR>15-30: event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR≤15: event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR>30-60 event rate, 6.8 for warfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR>15-30 event rate, 9.3 for warfarin vs 10.4 for no warfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR≤15 event rate, 9.1 for warfarin vs 13.5 for no warfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR>60 event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR>30-60 event rate, 53.6 for warfarin vs 69.0 for no warfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR>15-30 event rate, 90.2 for warfarin vs 117.7 for no warfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR≤15 event rate, 86.2 for warfarin vs 138.2 for no warfarin; HR, 0.55 (95% CI, 0.37-0.83).. Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Patient Readmission; Prospective Studies; Registries; Renal Insufficiency, Chronic; Risk; Stroke; Sweden; Thromboembolism; Warfarin

Previous studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of d-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.. In a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for d-dimer, tPA, and tPA/PAI-1 complex.. In multivariate Cox regression analysis, high levels of d-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01-1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05-1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06-1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.. We conclude that high levels of d-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Proportional Hazards Models; Warfarin

Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu.. Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median.. At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01).. This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.

Topics: Aged; Anticoagulants; Aorta, Thoracic; Cardiovascular Diseases; Disease Progression; Female; Follow-Up Studies; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Pulse Wave Analysis; Quebec; Renal Dialysis; Risk Factors; Survival Rate; Time Factors; Vascular Stiffness; Warfarin

We present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study.. We used a self-controlled case series to estimate the incidence rate ratio (IRR) comparing the rate of INR measurements of ≥4.0 in concomitant tramadol and VKA-exposed periods to VKA-only-exposed periods. Secondary analyses considered specific subgroups, alternative exposure criteria, alternative outcome definitions, and other drugs.. We identified 513 VKA users with at least 1 INR measurement ≥4.0 and concomitant tramadol and VKA exposure during the observation period. The overall IRR was 1.80 (95% confidence interval [CI], 1.53-2.10), with a stronger association among users of phenprocoumon compared to warfarin (IRR, 3.37; 95%CI, 2.50-4.53 and IRR, 1.46; 95%CI, 1.20-1.76, respectively). We observed larger IRRs with stricter outcome definitions. Concomitant tramadol and VKA exposure was also associated with an increased rate of low INR measurements (i.e., <1.5; IRR, 1.70; 95%CI, 1.37-2.13). Morphine and, to some extent, oxycodone, penicillin, beta-blockers, and inhaled beta-agonists were associated with high INR.. The approach successfully identified an interaction between tramadol and VKA. However, associations observed for other drugs with no known VKA interaction suggest that the current approach may have too low specificity to be useful as a screening tool, at least for drugs for which time-varying confounding may be present.

Topics: Age Factors; Aged; Aged, 80 and over; Analgesics, Opioid; Anticoagulants; Cardiovascular Diseases; Codeine; Denmark; Drug Interactions; Female; Humans; Insurance Claim Review; International Normalized Ratio; Male; Pharmacoepidemiology; Phenprocoumon; Prescription Drugs; Sex Factors; Tramadol; Vitamin K; Warfarin

To describe the baseline characteristics and antithrombotic treatment of patients with non-valvular atrial fibrillation in the Chinese subgroup of GRAFIELD.. GARFIELD is an observational registry study for patients with newly diagnosed non-valvular atrial fibrillation. A total of 805 adult ( ≥18 years old) patients (mean age: (66.6 ± 11.4) years old, 39.4% female (n = 317)) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks were recruited between December 2009 and October 2011 at 29 hospitals from China. Baseline data included demographics, medical history, nature of atrial fibrillation, CHA(2)DS(2) score, CHA(2)DS(2)-VASc score, and treatment at the time of diagnosis.. There were 216 patients (26.8%) with age above 75 years old, 116 patients (14.4%) had history of stroke or TIA, 261 patients (32.4%) had coronary artery disease. Mean CHADS(2) score was 1.7 ± 1.1, and 391 patients (48.5%) had a CHADS(2) score ≥ 2. Mean CHA(2)DS(2)-VASc score was 2.9 ± 1.7, and 630 patients (78.3%) had a CHA(2)DS(2)-VASc score ≥ 2.Overall, 159 patients (19.8%) received no anticoagulant treatment, 51.6% (n = 415) patients received aspirin and only 28.7% (n = 231) patients received either warfarin (n = 179, 22.2%) or new oral anticoagulants (NOAC) (n = 52, 6.5%). Among patients with CHADS2 score ≥ 2 (n = 391), 68.3% patients (n = 267) did not receive anticoagulant therapy. Among patients with CHA(2)DS(2)-VASc ≥ 2 (n = 630), 71.7% (n = 452) did not receive anticoagulant therapy. For the patients with very high risk of stroke, i.e. CHA(2)DS(2)-VASc ≥ 6, the proportion of the patients received NOAC and warfarin were identical (14.9%, 7/47).. This contemporary observational registry study shows that the anticoagulant therapy is somehow improved but still underused in Chinese NVAF patients. Stroke prevention according to risk scores and current guidelines in these patients remains an important task in China.

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cardiovascular Diseases; China; Female; Humans; Male; Middle Aged; Registries; Risk Assessment; Risk Factors; Stroke; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Thromboembolism; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Thromboembolism; Warfarin

The tale of dabigatran sounds some cautionary notes about proper critical appraisal of new randomised controlled trials,care in deciding on the generalisability of results, judicious screening of patients and lessons about the politics around increasingly lucrative drugs. The old lesson of caveat utilitor still holds: let the user beware!

Topics: Advertising; Anticoagulants; Antithrombins; Aspirin; Australia; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Dabigatran; Drug Interactions; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency; Research Design; Selection Bias; Stroke; Warfarin

Alternative anticoagulants to warfarin (dabigatran, rivaroxaban, and apixaban) are becoming available for the prevention of thromboembolic stroke in atrial fibrillation (AF), but there is a lack of information on their comparative effectiveness. Using a discrete event simulation method adopting a lifetime horizon of analysis, we made an indirect comparison of the RE-LY, ROCKET-AF, and ARISTOTLE trial results for AF patients in the US population. Over a lifetime, apixaban, dabigatran, and rivaroxaban accrued 0.130 (95% central range (CR) -0.030 to 0.264), 0.106 (95% CR -0.048 to 0.248), and 0.095 (95% CR -0.052 to 0.242) more quality-adjusted life-years (QALYs), respectively, than warfarin, with apixaban having a 55% probability of accruing the highest total QALYs. In the absence of a definitive trial, and acknowledging the limitations of an indirect comparison, the available evidence suggests apixaban to be the most effective anticoagulant.

Topics: Age Factors; Aged; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Comorbidity; Computer Simulation; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Time Factors; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Clopidogrel; Genetic Testing; Humans; Pharmacogenetics; Platelet Aggregation Inhibitors; Precision Medicine; Ticlopidine; Warfarin

To determine the impact of four NPS MedicineWise programs targeting quality use of medicines in cardiovascular management in primary care.. Interrupted time-series analysis using the Department of Veterans' Affairs (DVA) claims dataset from 1 January 2002 to 31 August 2010. We examined the use of antithrombotics in people with atrial fibrillation and in those who had had a stroke, and the use of echocardiography and spironolactone in the population with heart failure.. All veterans and their dependants in Australia who had received cardiovascular medicines or health services related to the targeted intervention.. NPS MedicineWise national programs to improve cardiovascular management in primary care, which included prescriber feedback, academic detailing, case studies and audits as well as printed educational materials.. Changes in medication and health service use before and after the interventions.. All national programs were positively associated with significant improvements in related prescribing or test request practice. The interventions to improve the use of antithrombotics resulted in a 1.27% (95% CI, 1.26%-1.28%) and 0.63% (95% CI, 0.62%-0.64%) relative increase in the use of aspirin or warfarin in the population with atrial fibrillation 6 and 12 months after the program, respectively, and in a 1.51% (95% CI, 1.49%-1.53%) relative increase in the use of aspirin as monotherapy for secondary stroke prevention 12 months after the intervention. The heart failure programs resulted in a 3.69% (95% CI, 3.67%-3.71%) relative increase in the use of low-dose spironolactone and a 4.31% (95% CI, 4.27%-4.35%) relative increase in the use of echocardiogram tests 12 months after the intervention.. NPS MedicineWise programs were effective in achieving positive changes in medicine and health service use for patients with cardiovascular diseases.

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Australia; Cardiovascular Diseases; Databases, Factual; Disease Management; Drug Utilization; Female; Humans; Male; Middle Aged; National Health Programs; Primary Health Care; Program Evaluation; Quality Improvement; Retrospective Studies; Survival Analysis; Treatment Outcome; Warfarin

Warfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non genetic factors on warfarin dosage in a South Italian population in the attempt to setup an algorithm easily applicable in the clinical practice.. A total of 266 patients from Southern Italy affected by cardiovascular diseases were enrolled and their clinical and anamnestic data recorded. All patients were genotyped for CYP2C9 2, 3, CYP4F2 3, VKORC1 -1639 G>A by the TaqMan assay and for variants VKORC1 1173 C>T and VKORC1 3730 G>A by denaturing high performance liquid chromatography and direct sequencing. The effect of genetic and not genetic factors on warfarin dose variability was tested by multiple linear regression analysis, and an algorithm based on our data was established and then validated by the Jackknife procedure.. Warfarin dose variability was influenced, in decreasing order, by VKORC1-1639 G>A (29.7%), CYP2C9 3 (11.8%), age (8.5%), CYP2C9 2 (3.5%), gender (2.0%) and lastly CYP4F2 3 (1.7%); VKORC1 1173 C>T and VKORC1 3730 G>A exerted a slight effect (<1% each). Taken together, these factors accounted for 58.4% of the warfarin dose variability in our population. Data obtained with our algorithm significantly correlated with those predicted by the two online algorithms: Warfarin dosing and Pharmgkb (p<0.001; R(2) = 0.805 and p<0.001; R(2) = 0.773, respectively).. Our algorithm, which is based on six polymorphisms, age and gender, is user-friendly and its application in clinical practice could improve the personalized management of patients undergoing warfarin therapy.

Topics: Aged; Algorithms; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Genotype; Humans; International Normalized Ratio; Italy; Male; Middle Aged; Pharmacogenetics; Polymerase Chain Reaction; Regression Analysis; Vitamin K Epoxide Reductases; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cardiovascular Diseases; Female; Humans; Warfarin

Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC-treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all-cause mortality.. A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow-up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41-4.56) for major bleeding and HR 2.19 (95% CI 1.38-3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40-2.01) and all-cause mortality (HR 1.77, 95% CI 1.52-2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high-sensitivity C-reactive protein and creatinine.. Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all-cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cause of Death; Cohort Studies; Female; Follow-Up Studies; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; von Willebrand Factor; Warfarin

Topics: Anticoagulants; Benzimidazoles; Cardiovascular Diseases; Dabigatran; Drug Approval; Drug Interactions; Food-Drug Interactions; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Warfarin

Topics: Aspirin; Blood Coagulation; Cardiovascular Diseases; Coronary Artery Disease; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Preoperative Period; Stroke; Thrombosis; Warfarin

We investigated the effect of clot activators carried over from the serum tube on major coagulation tests during phlebotomy. First, blood specimens from 30 normal subjects were mixed with small amounts of fluid containing clot activators, and their effects on various coagulation tests were determined. Only the value of fibrin monomer complex displayed a remarkable change when thrombin-containing fluid was added to the blood specimens. Subsequently, 100 paired blood specimens (taken from 75 healthy volunteers and 25 patients taking warfarin) were collected in coagulation tubes before and after the serum tube using standard phlebotomy procedures. Various coagulation tests were performed to determine the effect of contamination of thrombin-containing blood on coagulation parameters. Differences between the 2 tubes were minimal but significant for some of the coagulation tests. Therefore, we conclude that the effect of clot activators in the serum tube on coagulation tests is minimal when standard phlebotomy procedures are used.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Cardiovascular Diseases; Hemostatics; Humans; Phlebotomy; Thrombin; Warfarin

Evidence-based guidelines should in most cases be followed also in the treatment of elderly. Older people are often suboptimally treated with the recommended drugs.. To describe how well general practitioners adhere to current guidelines in the treatment of elderly with cardiovascular disease and evaluate local education as a tool for improvement.. Data was collected from the medical records of patients aged ≥ 65, who visited a primary health care center in Sweden 2006 and had one or more of the following diagnoses: hypertension, ischemic heart disease, heart failure, chronic atrial fibrillation, or prior stroke. Local education was organized and included feed-back to the patient's doctor and discussion about regional guidelines. Repeated measurements were performed in 2008.. The adherence to guidelines was low. Approximately one-third of the patients with hypertension reached target blood pressure, stroke patients more often. More patients with heart failure were treated with angiotensin converting enzyme inhibitor than in other European countries, but still only 60%. Half of the patients with chronic atrial fibrillation were treated with Warfarin, although more than two-thirds had a CHADS(2) score indicating the need. Educational efforts appeared to increase the adherence and hence should be encouraged.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Pressure; Cardiovascular Diseases; Chronic Disease; Evidence-Based Practice; General Practice; General Practitioners; Guideline Adherence; Heart Failure; Humans; Hypertension; Patient Compliance; Stroke; Warfarin

Oral anticoagulant (OA) medication is the recommended therapy for reducing the risk of thromboembolic complications in patients with atrial fibrillation (AF), and warfarin is the medication most frequently used. However, nonadherence associated with OA medications may lead to considerable health risks. A conceptual model of OA medication adherence in patients with AF could clarify factors affecting adherence, thereby assisting in the development and structuring of adherence-promotion programs. To our knowledge, such a model, driven by information obtained directly from patients, has never been developed.. To develop a conceptual model of adherence to OA medication based on a literature review and patient feedback via qualitative research among patients with AF.. A literature search was conducted of English-language articles published between the years 2005 and 2010 that related to factors affecting OA medication adherence, excluding articles pertaining to AF associated with mechanical heart valve replacement. To expand on the literature review findings, 4 focus groups totaling 38 participants aged 60 years or older, diagnosed with nonvalvular AF, and currently taking any OA medication were conducted in 2011. Participants completed the Modified Morisky Scale (MMS), with subscales measuring motivation and knowledge, and were asked about daily processes and behaviors related to taking OA medication. The identification of focus group themes was based on the frequency of participant report and endorsement; themes were spontaneously mentioned or supported by at least 2 people in each of at least 3 focus groups. Model concepts, based on focus group themes and factors identified in the literature review, were determined by the consensus of 3 authors.. 181 publications were identified; 30 were selected for full-text review. The focus group participants had a mean age of 69.9 years. Most participants reported a diagnosis of hypertension (86.8%, n=33), high cholesterol (50.0%, n=19), heart disease or chronic heart failure (31.6%, n=12), or diabetes (28.9%, n=11). Most (89.5%, n=34) were taking warfarin. About one-half (52.6%, n=20) had been taking an OA medication for less than 5 years. On the MMS, 78.9% of participants reported high levels of motivation, and 100% reported high levels of knowledge. Four concepts emerged from the focus groups and were supported by the literature for inclusion in the model: (a) knowledge base of the disease and continued reinforcement (i.e., health care professional reinforcement); (b) short-term and long-term motivation (e.g., avoidance of negative health consequences); (c) personalized system, habit formation, and system adaptation (e.g., developing a routine or external reminders); and (d) self-efficacy loop (i.e., the personalized system and its adaptability are reinforced as patients become more consistent, confident, and adherent). The literature review also suggested other factors that may also affect patient adherence (e.g., demographic, psychosocial, cognitive).. Adherence in patients with AF is complex and involves multiple factors, some specific to each individual and others more general. This model identifies an adherence process that can guide opportunities for effective interventions, such as educational and behavioral programs targeted at these processes, to improve patient adherence to OA medication.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Focus Groups; Health Knowledge, Attitudes, Practice; Humans; Male; Medication Adherence; Middle Aged; Models, Psychological; Motivation; Self Efficacy; Socioeconomic Factors; Stroke; Warfarin

The need for anticoagulation after surgical aortic valve replacement (AVR) with biological prostheses is not well examined.. To perform a nationwide study of the association of warfarin treatment with the risk of thromboembolic complications, bleeding incidents, and cardiovascular deaths after bioprosthetic AVR surgery.. Through a search in the Danish National Patient Registry, 4075 patients were identified who had bioprosthetic AVR surgery performed between January 1, 1997, and December 31, 2009. Concomitant comorbidity and medication were retrieved. Poisson regression models were used to determine risk.. Incidence rate ratios (IRRs) of strokes, thromboembolic events, cardiovascular deaths, and bleeding incidents by discontinuing warfarin as opposed to continued treatment 30 to 89 days, 90 to 179 days, 180 to 364 days, 365 to 729 days, and at least 730 days after surgery.. The median duration of follow-up was 6.57 person-years. Estimated rates of events per 100 person-years in patients not treated with warfarin compared with those treated with warfarin with comparative absolute risk were 7.00 (95% CI, 4.07-12.06) vs 2.69 (95% CI, 1.49-4.87; adjusted IRR, 2.46; 95% CI, 1.09-5.55) for strokes; 13.07 (95% CI, 8.76-19.50) vs 3.97 (95% CI, 2.43-6.48; adjusted IRR, 2.93; 95% CI, 1.54-5.55) for thromboembolic events; 11.86 (95% CI, 7.81-18.01) vs 5.37 (95% CI, 3.54-8.16; adjusted IRR, 2.32; 95% CI, 1.28-4.22) for bleeding incidents; and 31.74 (95% CI, 24.69-40.79) vs 3.83 (95% CI, 2.35-6.25; adjusted IRR, 7.61; 95% CI, 4.37-13.26) for cardiovascular deaths within 30 to 89 days after surgery; and 6.50 (95% CI, 4.67-9.06) vs 2.08 (95% CI, 0.99-4.36; adjusted IRR, 3.51; 95% CI, 1.54-8.03) for cardiovascular deaths within 90 to 179 days after surgery.. Discontinuation of warfarin treatment within 6 months after bioprosthetic AVR surgery was associated with increased cardiovascular death.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Bicuspid Aortic Valve Disease; Cardiovascular Diseases; Denmark; Drug Administration Schedule; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Incidence; Male; Middle Aged; Registries; Risk; Stroke; Thromboembolism; Warfarin

Topics: Anticoagulants; Aortic Valve; Bicuspid Aortic Valve Disease; Cardiovascular Diseases; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Thromboembolism; Warfarin

To estimate the risk of hemorrhagic complications associated with 25-gauge pars plana vitrectomy (PPV) when warfarin (Coumadin; Bristol-Myers Squibb, New York, NY) or clopidogrel (Plavix; Bristol-Myers Squibb) are continued throughout the surgical period, as compared with a control group.. A single-center, retrospective, cohort study of 289 consecutive patients receiving either warfarin therapy or clopidogrel therapy or neither of those therapies who underwent 25-gauge PPV.. Included were 61 patients (64 eyes; 64 PPV procedures) in the warfarin group and 118 (125 eyes; 136 PPV procedures) in the clopidogrel group. Warfarin patients were subdivided into 4 groups by international normalized ratio (INR). A control group included 110 patients (110 eyes; 110 PPV procedures) who were not receiving warfarin or clopidogrel.. Retrospective chart review for which the criteria included: 25-gauge PPV, minimum age of 19 years, warfarin or clopidogrel use, and, if taking warfarin, an INR obtained within 5 days of surgery.. Incidence of intraoperative and postoperative hemorrhagic complications.. The most common indications for anticoagulation therapy included: atrial fibrillation (38%), valvular heart disease (17%), and thromboembolic disease (16%). The most common indications for antiplatelet therapy included: cardiac stent (49%), coronary artery bypass grafting (24%), and history of transient ischemic attack (16%). No patient experienced anesthesia-related hemorrhagic complications resulting from peribulbar or retrobulbar block. Transient vitreous hemorrhage occurred in 1 (1.6%) of 64 PPV procedures in the warfarin group (P = 0.6531), 5 (3.7%) of 136 PPV procedures in the clopidogrel group (P = 1.0), and 4 (3.6%) of 110 PPV procedures in the control group. No choroidal or retrobulbar hemorrhages occurred in any patient.. The rate of 25-gauge PPV hemorrhagic complications in patients who underwent systemic anticoagulation or who were receiving platelet inhibitor therapy is extremely low. Given the risks associated with stopping these therapies, the authors recommend that patients continue their current therapeutic regimen without cessation.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Choroid Hemorrhage; Clopidogrel; Humans; Incidence; Intraocular Pressure; Intraoperative Complications; Microsurgery; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Retinal Diseases; Retrobulbar Hemorrhage; Retrospective Studies; Risk Factors; Ticlopidine; Visual Acuity; Vitrectomy; Vitreous Hemorrhage; Warfarin

A pro-thrombotic condition was described in 1983 which was characterised by the presence of circulating antiphospholipid antibodies, as well as peripheral thrombosis (e.g. DVT), a tendency to internal organ involvement, repeated miscarriage, and, occasionally, thrombocytopenia (aPL) (Hughes, Br Med J 287:1088-1089, 1983). Previously, there had been a number of observations, mainly in patients with lupus having "false positive" tests for syphilis, miscarriage and circulating lupus anticoagulants. The description in 1983 had three notable features (a) a detailed comprehensive clinical picture of the syndrome; (b) this description differed from other coagulopathies in showing a propensity for arterial thrombosis (e.g. stroke and heart attack); and (c) this was a syndrome quite independent from lupus. There are indications that the primary antiphospholipid syndrome will turn out to be more common than lupus, though this could still be a reflection of referral practice.

Topics: Abortion, Spontaneous; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Arterial Occlusive Diseases; Aspirin; Brain Diseases; Cardiovascular Diseases; Constriction, Pathologic; Female; Heparin, Low-Molecular-Weight; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infarction; Pregnancy; Thrombosis; Warfarin

While Hispanics are the largest and most rapidly growing minority population in the United States, they are underrepresented in pharmacogenomic studies with warfarin. We sought to determine the combination of clinical and genetic influences of warfarin dose requirements in Hispanics. In addition, we tested the performance of published warfarin dosing algorithms derived from largely non-Hispanic cohorts in an inner-city U.S. Hispanic population. Genetic samples and clinical data were obtained from 50 Hispanics on a stable dose of warfarin. The contribution of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex-1 (VKORC1) genotypes and clinical factors to warfarin dose requirements was determined. The correlation between the predicted dose using published algorithms and therapeutic dose was also assessed. Compared to the VKORC1-1639 GG genotype, warfarin dose requirements were 30% and 62% lower with the GA and AA genotypes, respectively (p=0.001). The combination of the VKORC1-1639G>A and CYP2C9 genotypes and clinical factors explained 56% of the inter-patient variability in warfarin dose. Warfarin dose predicted using algorithms derived from mostly non-Hispanic cohorts was significantly correlated with the therapeutic dose in our Hispanic cohort (r(2)=0.43 to 0.49; p<0.001); the predicted dose was within 1.0 mg/day of the therapeutic dose for 40% to 50% of patients. Our data suggest that factors influencing warfarin dose requirements in Hispanic Caucasians are similar to those previously described in European Caucasians and that dosing algorithms derived from non-Hispanic Caucasian cohorts are applicable to Hispanics living in the U.S.

Topics: Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Genotype; Hispanic or Latino; Humans; Male; Middle Aged; Mixed Function Oxygenases; Pharmacogenetics; Polymorphism, Genetic; United States; Vitamin K Epoxide Reductases; Warfarin; White People

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Double-Blind Method; Education, Medical; Evidence-Based Medicine; Humans; Practice Guidelines as Topic; Warfarin

The individual management of anticoagulation therapy is important for safe medical outcomes, including those of oral surgery. Here, Japanese patients who received warfarin (n = 35) and normal controls (n = 125) were analyzed by real-time PCR to determine the frequencies of single nucleotide polymorphisms in VKORC1 (vitamin K epoxide reductase complex, subunit 1) and CYP2C9 and how these frequencies related to warfarin dose and PT-INR. The genetic polymorphisms CYP2C9(*2) (416 C > T), CYP2C9(*3) (1061 A > C), and intron 1-136 C > T in VKORC1 (1173 C > T) were measured. All patients had the wild-type CYP2C9 gene (*1/*1). All 160 cases had the wild-type (CC) type CYP2C9(*2), 93.8% had AA type CYP2C9(*3), 6.2% had AC type CYP2C9(*3), 1.2% had CC type VKORC1, 13.8% had CT type VKORC1, and 85% had TT type VKORC1. The CC type VKORC1 genetic polymorphism was associated with a significantly higher mean warfarin maintenance dose (4.5 ± 0.5 mg) than other VKORC1 genotypes (TT type 2.9 ± 0.1 mg: CT type 3.4 ± 0.3 mg). Categorization of the patients in terms of the combined CYP2C9 and VKORC1 haplotype (the warfarin-responsive index; WRI) revealed the mean daily warfarin maintenance dose was 3.0 ± 0.1 mg for WRI 1 and 3.7 ± 0.3 mg for WRI 2 (P < 0.012). The event survey revealed 2 patients with nonfatal cerebral hemorrhage had a WRI score of 2 (VKORC1 C/T heterozygosity genotype). Thus, CYP2C9 and VKORC1 haplotype analysis allows prediction of warfarin maintenance dosage. The findings may provide a personalized use of warfarin in the field of oral surgery.

Topics: Aged; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Case-Control Studies; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Genetic Markers; Genotype; Haplotypes; Humans; Introns; Male; Middle Aged; Mixed Function Oxygenases; Oral Surgical Procedures; Polymorphism, Single Nucleotide; Predictive Value of Tests; Sensitivity and Specificity; Treatment Outcome; Vitamin K Epoxide Reductases; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Defibrillators, Implantable; Echocardiography, Transesophageal; Heart Atria; Heart Diseases; Heart Transplantation; Humans; Magnetic Resonance Imaging; Thrombosis; Tomography, X-Ray Computed; Warfarin

What's known on the subject? and What does the study add? There is controversy over the use of anti-platelet and anti-coagulant drugs in men undergoing TURP with contradictory evidence on the effect of the drugs on bleeding following the operation, particularly for aspirin. If anti-platelet or anti-coagulant drugs are not stopped for TURP, there is an unacceptable burden of bleeding. If the drugs are stopped there is an unacceptable rate of cardiovascular events.. • To determine the morbidity associated with perioperative management of antiplatelet (AP) or anticoagulant (AC) medication and transurethral prostatectomy.. • A retrospective review was performed on 163 consecutive patients undergoing transurethural prostatectomy. • Patients were grouped according to the perioperative management of AP and AC medications: control patients not prescribed any AP/AC drugs (group 1), those on AP/AC who had ceased them perioperatively (group 2) and those whose AP/AC were continued (group 3). • Warfarin was withheld perioperatively for all patients. • Morbidity associated with increased blood loss and cardiovascular or cerebrovascular events was recorded and differences were analysed with SPSS version 16 software.. • There was a statistically significant increase in bleeding-associated morbidity in group 2 (13/65) and group 3 (6/7) compared with the controls (9/91) (P < 0.01). • Cardiovascular and cerebrovascular events were only seen in group 2 (6/65), statistically significantly higher than the event rate in the other groups (P ≤ 0.01). • All cardiovascular or cerebrovascular events occurred in patients prescribed these medications for secondary prevention.. • Patients taking AP or AC medications have a higher rate of perioperative bleeding compared with those who are not taking any. • However, for patients prescribed AP or AC medication for secondary prevention, withholding these medications results in an increased rate of cardiovascular and cerebrovascular complications. • Careful consideration of the risks and other management options should be undertaken before performing transurethural prostatectomy in this high risk group of patients.

Topics: Aged; Anticoagulants; Aspirin; Blood Loss, Surgical; Cardiovascular Diseases; Case-Control Studies; Cerebrovascular Disorders; Humans; Male; Perioperative Care; Platelet Aggregation Inhibitors; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies; Transurethral Resection of Prostate; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Echocardiography; Electrocardiography, Ambulatory; Embolism; Exercise Test; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticlopidine; Warfarin

Although combination therapy for various cardiac conditions with dual antiplatelet therapy (aspirin and thienopyridine derivatives) and warfarin sodium has become increasingly popular, the safety and effectiveness of this aggressive treatment regimen remain unknown.. We retrospectively enrolled and analyzed 575 consecutive patients who had been implanted with drug-eluting coronary stents. The primary and secondary endpoints were major bleeding complications and major adverse cardiovascular events (MACE), respectively. At the time of discharge, 525 patients (91.3%) were prescribed with dual antiplatelet therapy, and 50 (8.7%) of them received dual antiplatelet plus anticoagulant therapy (triple therapy). The patients treated with triple therapy had a greater prevalence of comorbid conditions, including left ventricular systolic dysfunction and multi-vessel coronary disease compared to those on the dual antiplatelet regimen. During a median follow-up of 459 days, 14 (2.7%) patients receiving dual, and 9 (18.0%) receiving triple therapy reached the primary endpoint (p<0.001). These results show that warfarin use was associated with an increased risk of subsequent major bleeding. On the other hand, the incidence of MACE did not differ between the two groups (p=0.108 by the log-rank test). Multivariate analysis showed that renal impairment was an independent predictor of the risk of subsequent major bleeding in the triple therapy group.. Triple therapy increased the hemorrhagic complications in patients after percutaneous coronary intervention with drug-eluting stents, especially in patients with impaired renal function. Great caution should be taken with patients who necessitate the addition of anticoagulation therapy with warfarin to dual antiplatelet therapy.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Cardiovascular Diseases; Coronary Disease; Drug-Eluting Stents; Female; Hemorrhage; Humans; Kidney Diseases; Male; Platelet Aggregation Inhibitors; Prognosis; Pyridines; Retrospective Studies; Ventricular Dysfunction; Warfarin

Topics: Aged; Alcohol Drinking; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Asian People; Cardiovascular Diseases; Cohort Studies; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; International Normalized Ratio; Japan; Male; Middle Aged; Mixed Function Oxygenases; Pharmacogenetics; Polymorphism, Genetic; Smoking; Vitamin K Epoxide Reductases; Warfarin

Aim of the work was selection of optimal for patients in Russia algorithm of warfarin dosing based on results of pharmacogenomic testing. We analyzed data from 78 patients aged 63.4+/-9.4 years with known CYP29 and VKORC1 genotypes who had participated in an earlier retrospective study in which they received warfarin according to traditional scheme with starting dose of 5 mg/day. We used 5 known algorithms of determination of initial warfarin dose based on results of pharmacogenomic testing and correlated calculated doses with those which had been actually selected in our patients. Correlation was closest for doses obtained with algorithm of Gage et al (www.warfarindosing.org) (r=0.887, p<0.0001). Therefore we consider this algorithm most suitable for patients in Russia.

Topics: Algorithms; Anticoagulants; Cardiovascular Diseases; Dose-Response Relationship, Drug; Humans; Middle Aged; Precision Medicine; Retrospective Studies; Russia; Warfarin

The aim of this study was to determine if warfarin should be withdrawn before a single tooth extraction on a patient with a prosthetic heart valve.. A quantitative decision tree was constructed to assess the expected utility values of 2 typical strategies to manage the dental extraction on a patient currently medicated with warfarin. Probabilities and utilities for a cardiovascular accident and major bleeding from a dental extraction were taken from the literature.. The decision slightly favors withholding warfarin: generating an optimal expected utility value of 0.976 utile. This was only 0.02 utile higher than the alternative option of continuing warfarin for a dental extraction.. The decision to withhold or continue warfarin before a dental extraction depends more on the relative risk of a major bleeding between the 2 medical management strategies than on the consequences of a cardiovascular accident.

Topics: Anticoagulants; Cardiovascular Diseases; Cause of Death; Decision Trees; Heart Valve Prosthesis; Hemostasis, Surgical; Hemostatics; Humans; Middle Aged; Postoperative Complications; Postoperative Hemorrhage; Probability; Risk Assessment; Stroke; Tooth Extraction; Treatment Outcome; Warfarin

Case reports suggest an association between cranberry juice and potentiation of warfarin. Studies using 240 ml of cranberry juice daily demonstrated no interaction. It is unknown if higher amounts of cranberry juice will interact with warfarin.. Cranberry juice at 240 ml twice daily does not alter the pharmacodynamics of warfarin.. To determine if high-dose cranberry juice (240 ml twice daily) alters the pharmacodynamic action of warfarin.. Ten male patients taking stable doses of warfarin were given cranberry juice at 240 ml twice daily for 7 days. Prothrombin times were drawn at baseline and days 2, 6 and 8 after administration of the juice. Prothrombin times were averaged for each day and mean times were compared from each study day to baseline using repeated measures ANOVA.. There was no statistical difference between mean prothrombin time at baseline and any day tested during juice administration.. Cranberry juice (240 ml twice daily for 1 week) did not alter the pharmacodynamics of warfarin in patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Food-Drug Interactions; Humans; Male; Middle Aged; Prospective Studies; Prothrombin Time; Vaccinium macrocarpon; Warfarin

Topics: Anticoagulants; Benzimidazoles; Carboxypeptidase B2; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Dabigatran; Fibrinolytic Agents; Humans; Morpholines; Pyridines; Receptor, PAR-1; Rivaroxaban; Thiophenes; Thrombin; Thrombomodulin; Thrombosis; Treatment Outcome; Warfarin

Patient self-testing (PST) of the international normalised ratio (INR) has a positive effect on anticoagulation control. This study investigated whether the benefits of PST (other than increased frequency of testing, e.g. patient education, empowerment, compliance etc.) could be 'carried-over' into usual care management after a period of home-testing has ceased.. Patients that completed a six month period of PST (as part of a randomised controlled trial) but returned to clinic management when the trial ended were included in the study. The primary outcome variable was the difference in anticoagulation control (measured using the time in therapeutic range) between the two periods. A group of patients who were managed solely by the anticoagulation clinic served as the control.. There was no significant difference in median time in therapeutic range (TTR) between the 52 patients during clinic management post-PST and the six month period of PST (75% vs 75.3%; p=0.061). Patients tested more frequently while home-testing compared with the subsequent six month period of clinic management (once every 5.6±0.7days compared with once every 23.2±7.4days; p=0.000). Patients with previous experience of PST performed significantly better than the control group of patients (n=107) that were managed solely by the anticoagulation clinic (75% vs 59.7%; p=0.009) despite less frequent monitoring of the INR (every 23.2±7.4days vs. 17.4±6.7days; p=0.000).. The improvements in anticoagulation control observed during a period of PST can be sustained when patients cease home-testing and revert back to usual care management.

Topics: Anticoagulants; Cardiovascular Diseases; Diagnostic Self Evaluation; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin Time; Quality of Health Care; Retrospective Studies; Warfarin

The authors investigated the use of warfarin at hospital discharge in 557 consecutive patients, mean age 76 years, with nonvalvular atrial fibrillation (AF) at a university hospital. Of 557 patients with AF, 116 (21%) had contraindications to warfarin. Of patients eligible for warfarin, warfarin was used in 8 of 30 patients (27%) with a CHADS(2) score of 0, in 82 of 132 patients (62%) with a CHADS(2) score of 1, in 121 of 175 patients (70%) with a CHADS(2) score of 2, in 72 of 77 patients (94%) with a CHADS(2) score of 3, and in 27 of 27 patients (100%) with a CHADS(2) score of 4 to 6. Warfarin was used in 123 of 168 patients (73%) older than 75 years, in 74 of 79 patients (94%) aged 65 to 75 years, and in 23 of 32 patients (72%) younger than 65 years. Warfarin was used in 80 of 116 patients (69%) with a glomerular filtration rate < 60 mL/min/1.73 m(2) and in 140 of 163 patients (86%) with a glomerular filtration rate ≥ 60 mL/min/1.73 m(2) . There was no significant difference in use of warfarin between men and women and between whites and nonwhites.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cardiovascular Diseases; Female; Fibrinolytic Agents; Health Status Indicators; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prevalence; Risk Factors; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Gene Expression Profiling; Genetic Testing; Humans; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Genetic factors account for 35-40% of the interindividual variation observed in response to warfarin. The most important genes involved are CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex subunit 1).. To determine the prevalence of the different genotypes influencing response to oral anticoagulants in a population of cardiovascular patients on chronic anticoagulation and to investigate the correlation between genotype and the warfarin dose required for optimal anticoagulation.. A total of 91 chronically anticoagulated consecutive patients were genotyped for CYP2C9 and VKORC1, using PCR and reverse hybridization.. Of the 91 patients, 57.1% were male and mean age was 67.4 +/- 13.1 years. most frequent indication for warf was atrial fibrillation (56.8%). We analyzed the prevalence of the different CYP2C9 and VKORC1 genotypes in this population and found that the warfarin doses required to maintain patients at their desired anticoagulation target were significantly different among carriers of the different genotypes.. Our study highlights the importance of genetic study in the clinical management of patients on chronic anticoagulation, increasing the safety and efficacy of warfarin therapy.

Topics: Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Cytochrome P-450 CYP2C9; Drug Monitoring; Female; Genotype; Humans; Male; Mixed Function Oxygenases; Vitamin K Epoxide Reductases; Warfarin

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Female; Foot Diseases; Humans; Pigmentation Disorders; Syndrome; Toes; Warfarin

The past few years have witnessed considerable advances in the field of cardiovascular pharmacogenomics, not least as a result of genome-wide surveys. We here briefly review recent advances supporting the value of genetic information in the treatment of patients with betablockers, statins and warfarin. Although definitive proof that genotyping can change outcomes of patients with cardiovascular diseases await randomised trials, personalised cardiovascular pharmacotherapy is on the verge of entering clinical practice.

Topics: Adrenergic beta-Antagonists; Anticholesteremic Agents; Anticoagulants; Cardiovascular Diseases; Cytochrome P-450 Enzyme System; Genetic Markers; Genotype; Humans; Pharmacogenetics; Treatment Outcome; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Clinical Trials as Topic; Clopidogrel; Female; Genetic Predisposition to Disease; Genetic Testing; Genetic Variation; Genome-Wide Association Study; Genomics; Humans; Pharmacogenetics; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticlopidine; Warfarin

1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of 1, 2, 3 and 4 CYP2C9 alleles, using a nested-allele-specific-multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9 1/1 and 6.8% were CYP2C9 1/3. Warfarin doses were higher in patients with CYP2C91/1. Patients with the 1/3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.

Topics: Aged; Alleles; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; China; Cytochrome P-450 CYP2C9; Female; Follow-Up Studies; Genotype; Hemorrhage; Humans; Malaysia; Male; Middle Aged; Pharmacogenetics; Retrospective Studies; Warfarin

We sought to determine the effect of anticoagulation therapy on outcomes in elderly patients with closed head injury. We retrospectively reviewed elderly closed head injury patients (> or = 65 years) comparing 52 patients on warfarin (AC) with 439 patients not on warfarin (NAC) with subsequent 1:3 propensity matching used to analyze comparable groups. The overall AC group had a higher head abbreviated injury score (AIS) (4.0 +/- 0.7 vs 3.8 +/- 0.7, P = 0.04) compared with the NAC group. After propensity matching, 49 AC patients were compared with 147 NAC patients who were similar for age, gender, injury severity score, and head AIS. Admission INR was higher in the AC group compared to the NAC group (2.5 +/- 1.3 vs 1.1 +/- 0.3, P < 0.0001) and the AC group had a higher mortality rate (38.8% AC (19/49) vs 23.1% NAC (34/147), P = 0.04). In the AC group, survivors and nonsurvivors had similar repeat International Normalized Ratio (INR) values (1.57 +/- 0.65 survivors vs 1.8 +/- 0.72 nonsurvivors, P = 0.31). The AC group experienced greater morbidity after trauma and had higher mortality rates than their NAC counterparts. Prevention of injury and more selective use of warfarin in this patient population are essential to decrease mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Craniocerebral Trauma; Female; Glasgow Coma Scale; Humans; Length of Stay; Male; Outcome Assessment, Health Care; Retrospective Studies; Warfarin

More elderly trauma patients are identified with preinjury use of clopidogrel, aspirin, or warfarin (CAW). The purpose of this study was to determine whether preinjury CAW use was an important predictor of mortality in patients aged >or=50 years with blunt, hemorrhagic brain injury (HBI).. A retrospective review of patients with blunt, HBI aged >or=50 years with subgroup analysis for older (>70 years) and younger (50-70 years) patients was performed. CAW use was analyzed for differences in age, gender, hospital length of stay (LOS), Injury Severity Score (ISS), Glasgow Coma Score (GCS), mechanism of injury (MOI), platelet transfusion therapy (PLT), disposition at discharge, and in-hospital mortality.. From January 2003 to October 2005, 416 patients were identified. The mean age was 69+/-1 years. No differences were found for ISS (24 +/- 0.5), GCS (12 +/- 0.2), or LOS (8 +/- 0.4 days). CAW use was present in 40% of patients and significantly higher in older patients. Mortality was not different between older and younger CAW(+) patients, but it significantly increased for older CAW(-) patients. Significant predictors of death included age, ISS, and GCS (P<.02).. Preinjury CAW use in older blunt, HBI patients is not associated with increased mortality. Age was a significant predictor of mortality independent of CAW use.

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Brain Hemorrhage, Traumatic; Cardiovascular Diseases; Cause of Death; Clopidogrel; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Geriatric Assessment; Hospital Mortality; Humans; Injury Severity Score; Male; Middle Aged; Platelet Aggregation Inhibitors; Preoperative Care; Retrospective Studies; Risk Assessment; Sex Factors; Survival Analysis; Ticlopidine; Trauma Centers; Treatment Outcome; Warfarin; Wounds, Nonpenetrating

Patients are living longer with cardiovascular disease managed with antiplatelet drugs. These seniors are asked to be more physically active and are prone to falls or injuries. Few have studied the mortality or morbidity from anticoagulants in patients with traumatic brain injuries (TBI). With the increasing use of clopidogrel in the elderly, studies on the consequences of TBI are warranted.. This is a retrospective case-controlled study using a trauma data registry of 3,817 closed head trauma cases (2001-2005). Patients with preinjury use of clopidogrel, aspirin or warfarin, and evidence of traumatic intracranial bleeding were identified (n = 131). These were compared with a frequency-matched control group (n = 178) with similar age, gender, Glasgow Coma Scale, and Injury Severity Scores. Main outcome measure included mortality, hospital or intensive care unit duration, and discharge disposition.. Of 131 patients on anticoagulants, patients on clopidogrel (n = 21) were more likely to die (OR = 14.7; 95% CI: 2.3-93.6) and be discharged to an inpatient long-term facility (OR = 3.25; 95%CI: 1.06-9.96). Length of hospital stay and intensive care unit stay were not different from control. Mortality in aspirin patients (n = 90) and warfarin patients (n = 20) did not differ from control. Warfarin patients had increased hospital and ICU stay (10.6 and 5.3 days) when compared with the control (4.7 and 0.9 days, respectively).. TBI patients on clopidogrel may have increased long-term disability and fatal consequences when compared with patients who are not on these drugs or on other anticoagulants. Patients on clopidogrel should be advised of safety when engaging in potentially dangerous activities to avoid the consequences of TBI.

Topics: Aged; Aspirin; Brain Damage, Chronic; Brain Injuries; Cardiovascular Diseases; Case-Control Studies; Clopidogrel; Disability Evaluation; Female; Glasgow Coma Scale; Humans; Length of Stay; Male; Platelet Aggregation Inhibitors; Prognosis; Registries; Retrospective Studies; Ticlopidine; Warfarin

A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes.. The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximately 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators.. The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases.

Topics: Cardiovascular Diseases; Community Health Services; Cooperative Behavior; Databases, Factual; Defibrillators, Implantable; Humans; National Heart, Lung, and Blood Institute (U.S.); Quality of Health Care; Research; United States; Warfarin

Perioperative management of bariatric surgical patients receiving chronic anticoagulation requires an understanding of potential hemorrhagic and thromboembolic risks. The aim of this study is to evaluate hemorrhagic and thromboembolic complications in morbidly obese patients who are on oral anticoagulation treatment and subsequently undergo laparoscopic bariatric surgery.. The medical records of all laparoscopic Roux-en-Y gastric bypass (LRYGB) patients from June 2001 to March 2006 were retrospectively reviewed. In addition, data of patients who received chronic anticoagulation therapy with Coumadin and underwent laparoscopic Roux-en-Y gastric bypass was analyzed. Clinical parameters included length of hospitalization, hemorrhagic complications, thromboembolic complications, conversion rate, reoperation, and blood transfusion.. During the study period, 1,700 consecutive patients underwent bariatric surgery for the treatment of morbid obesity. Of these, 21 patients were treated with chronic oral anticoagulation; 3 of the 21 (14%) had hemorrhagic complications: one patient had intraluminal hemorrhage and two patients had intraabdominal hemorrhage. Two patients required blood transfusion, and one patient underwent surgical reintervention. None of the 21 laparoscopic operations were converted to open procedures. There were no postoperative mortalities, and there were no thromboembolic events in this series.. Laparoscopic bariatric surgery can be performed relatively safely in morbidly obese patients who are treated with chronic oral anticoagulation. Even in the presence of bleeding, patients can be successfully treated without the need for reoperation.

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Chronic Disease; Gastric Bypass; Hemorrhage; Humans; Laparoscopy; Obesity, Morbid; Retrospective Studies; Thromboembolism; Time Factors; Warfarin

We sought to determine the incidence and severity of bleeding events in patients with stroke and cardiovascular diseases who were taking oral antithrombotic agents in Japan, where the incidence of hemorrhagic stroke is higher than in Western countries.. A prospective, multicenter, observational study was conducted; 4009 patients who were taking oral antithrombotic agents for stroke and cardiovascular diseases were enrolled. The patients were classified into 4 groups according to their antithrombotic treatment: the single antiplatelet agent group (47.2%); the dual antiplatelet agent group (8.7%); the warfarin group (32.4%); and the warfarin plus antiplatelet agent group (11.7%). The primary end point was life-threatening or major bleeding according to the MATCH trial definition.. During a median follow-up of 19 months, there were 57 life-threatening and 51 major bleeding events, including 31 intracranial hemorrhages. The annual incidence of the primary end point was 1.21% in the single antiplatelet agent group, 2.00% in the dual antiplatelet agent group, 2.06% in the warfarin group, and 3.56% in the warfarin plus antiplatelet agent group (P<0.001). After adjustment for baseline characteristics, adding an antiplatelet agent to warfarin increased the risk of the primary end point (relative risk=1.76; 95% CI, 1.05 to 2.95), and adding another antiplatelet agent to single antiplatelet agent therapy increased the secondary end point of any bleeding, including minor events (relative risk=1.37; 95% CI, 1.07 to 1.76).. The incidence of bleeding events during antithrombotic therapy in Japan was similar to that reported for Western countries, although the trials used different study designs. Dual antithrombotic therapy was independently related to an increased risk of bleeding events.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Causality; Cerebral Hemorrhage; Clinical Protocols; Comorbidity; Drug Combinations; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Incidence; Japan; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Stroke; Warfarin

Topics: Adrenal Cortex Hormones; Aging; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2 Inhibitors; Drug Administration Schedule; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Ulcer; Warfarin

To assess the incidence of bleeding after dental extractions in subjects taking warfarin continuously before and after extractions whose International Normalised Ratio (INR) was below 4.0 at the time of extraction.. This was a case series study of 150 patients without controls who required extraction of at least one tooth under local anaesthetic. All sockets were subsequently packed with absorbable oxycellulose and sutured.. A total of 58 women and 92 men were included (mean age 66 years); their ages were similar. The mean INR (S.D.) was 2.5 (0.56), although most patients had an INR less than 2.5 (n=101). Ten patients (7%) bled after extraction, enough to require a return to hospital. Five patients of 101 with an INR2.5 out of 49 bled after extraction (p=0.29). Bleeding after extraction was not associated with operative antibiotics. All patients who bled were managed conservatively and none was admitted to hospital.. Patients taking warfarin whose INR is up to 4.0 and who have dental extractions in hospital do not have clinically significant bleeds post-operatively.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Dental Care for Chronically Ill; Female; General Practice, Dental; Humans; International Normalized Ratio; Male; Middle Aged; Oral Hemorrhage; Postoperative Hemorrhage; Retrospective Studies; Tooth Extraction; Warfarin

Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P-selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF.. We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively.. Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels.. There is evidence of platelet activation (ie, high PMP and sP-selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se.

Topics: Aged; Aspirin; Atrial Fibrillation; Blood Coagulation Factors; Blood Platelets; Cardiovascular Diseases; Case-Control Studies; Cell Membrane; Cerebral Infarction; Coronary Disease; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolytic Agents; Flow Cytometry; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; P-Selectin; Particle Size; Platelet Activation; Reference Values; Risk Factors; Statistics as Topic; Warfarin

Case report.. To describe a case of spinal epidural hematoma arising from the synovial joint due to anticoagulation therapy.. Spontaneous spinal epidural hematoma is a rarity in the literature with a variety of etiologies. In 1 study, it was reported to originate from a synovial joint due to osteoarthritis of the joint.. A case of hematoma of the lumber synovial joint is presented.. A 67-year-old man who was on anticoagulation therapy presented with progressive neurologic symptoms in the right lower limb. Magnetic resonance imaging scan revealed what was thought to be a L4-L5 synovial joint cyst. During surgery, it was proven to be an epidural hematoma originating from the synovial joint. Microscopic examination confirmed the diagnosis and excluded the possibility of spinal synovial cyst. After spinal decompression, neurologic symptoms improved completely in 2 weeks.. This is the first report of a synovial cyst hematoma due to anticoagulation therapy. Its magnetic resonance imaging features can be similar to synovial cyst, especially when it is hemorrhagic. Spinal decompression was the definitive treatment.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Diagnosis, Differential; Hematoma; Hematoma, Epidural, Spinal; Humans; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Synovial Cyst; Warfarin

Warfarin is a commonly prescribed anticoagulant drug used to prevent thromboses that may arise as a consequence of orthopedic and vascular surgery or underlying cardiovascular disease. Warfarin is associated with a notoriously narrow therapeutic window where small variations in dosing may result in hemorrhagic or thrombotic complications. To ultimately improve dosing of warfarin, we evaluated models for stable maintenance dose that incorporated both clinical and genetic factors.. A model was constructed by evaluating the contribution to dosing variability of the following clinical factors: age, gender, body surface area, and presence or absence of prosthetic heart valves or diabetes. The model was then sequentially expanded by incorporating polymorphisms of cytochrome P450 (CYP) 2C9; vitamin K 2,3 epoxide reductase complex, subunit 1 (VKORC1); gamma carboxylase; factor VII; and apolipoprotein (Apo) E genes.. Of genetic factors evaluated in the model, CYP2C9 and VKORC1 each contributed substantially to dose variability, and together with clinical factors explained 56% of the individual variability in stable warfarin dose. In contrast, gamma carboxylase, factor VII and Apo E polymorphisms contributed little to dose variability.. The importance of CYP2C9 and VKORC1 to patient-specific dose of warfarin has been confirmed, while polymorphisms of gamma carboxylase, factor VII and Apo E genes did not substantially contribute to predictive models for stable warfarin dose.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Carboxylic Acids; Cardiovascular Diseases; Cytochrome P-450 CYP2C9; Drug Administration Schedule; Female; Genetic Testing; Humans; Male; Middle Aged; Mixed Function Oxygenases; Pharmacogenetics; Polymorphism, Genetic; Vitamin K Epoxide Reductases; Warfarin

In patients with premature atherothrombotic disease, the antiphospholipid syndrome (APS, defined as any thrombosis plus the repeated presence ofantiphospholipid antibodies) is sometimes looked for, as observational studies have suggested a link between APS and premature atherothrombosis. However, recent reviews that evaluated the prognostic value of antiphospholipid antibodies have concluded that the prognostic significance ofAPS for recurrent thrombotic disease is, at best, unclear and that its presence has no therapeutic consequences. A study that compared high- versus standard-dosage warfarin in patients with APS found no additional benefit from high-dosage warfarin. A study in patients with a recent ischaemic stroke found no additional benefit from warfarin (standard dosage) versus aspirin in patients with or without antiphospholipid antibodies. Therefore, on the basis of the evidence at hand, screening for APS in patients with premature atherosclerosis is not considered to be useful.

Topics: Antibodies, Antiphospholipid; Anticoagulants; Biomarkers; Cardiovascular Diseases; Dose-Response Relationship, Drug; Humans; Lupus Coagulation Inhibitor; Prognosis; Risk Factors; Thrombosis; Warfarin

Although warfarin and antiplatelet medications have documented efficacy for prevention of primary and secondary cardiovascular events, the appropriateness of warfarin and antiplatelet combination therapy is not well described in national consensus guidelines.. Cross-sectional data from 4,557 Kaiser Permanente Colorado members > or = 18 years old who were receiving warfarin anticoagulation therapy were used to quantify the prevalence of warfarin and antiplatelet agent (ie, aspirin, clopidogrel, dipyridamole, and/or dipyridamole/aspirin) combination therapy as of September 30, 2005, and to identify characteristics of patients receiving combination therapy. The prevalence of warfarin and any antiplatelet combination therapy was 385/1,000 (95% confidence interval [CI], 371/1,000 to 399/1,000). The majority of combination therapy was warfarin and aspirin (prevalence, 378/1,000) with a daily dose of aspirin, 81 mg, being the most reported dose (prevalence, 328/1,000). Patients receiving combination therapy were more likely to be male (63.6% vs 46.4%; adjusted odds ratio, 1.5; 95% CI, 1.3 to 1.7) and have a comorbidity of heart failure (29.0% vs 15.6%; adjusted odds ratio, 1.2; 95% CI, 1.1 to 1.5), coronary artery disease (62.4% vs 17.5%; adjusted odds ratio, 7.6; 95% CI, 6.5 to 8.8), and/or stroke/transient ischemic attack (5.2% vs 1.6%; adjusted odds ratio, 3.5; 95% CI, 2.3 to 5.3).. Nearly 4 of 10 patients receiving warfarin management care were receiving warfarin and antiplatelet combination therapy. The findings suggest that this practice is widespread, especially among patients with established cardiovascular disease, and involves a substantially higher number of patients than previously reported. The clinical outcomes associated with this practice require further investigation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cross-Sectional Studies; Drug Therapy, Combination; Drug Utilization Review; Female; Health Maintenance Organizations; Humans; Male; Middle Aged; Multivariate Analysis; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin

Vitamin K epoxide reductase (VKORC1) is the drug target for inhibition by coumarin-based anticoagulant drugs such as warfarin. Warfarin therapy has been reported as a leading cause of drug-related hospitalization and there is therefore an urgent need to develop tests for better warfarin prescription. We report here the distribution of the intron 1 -136 T>C (1173 T>C intron) polymorphism of VKORC1, previously reported to be associated with warfarin maintenance dose in Caucasians and Japanese, in several ethnic populations from Japan and Israel, and describe its significance for warfarin dosage in Japanese cardiovascular surgery patients.. Subjects consisted of 132 Japanese individuals and 341 Israeli individuals from four Jewish ethnic groups (86 Ashkenazi Jews, 95 Yemenite Jews, 73 Moroccan Jews and 87 Libyan Jews). In addition, 31 Japanese patients receiving warfarin therapy after cardiovascular surgery, maintained with a target International Normalized Ratio, were studied. The genotyping for the 1173 T>C intron polymorphism of VKORC1 was determined using rapid real-time PCR.. The allele frequency of the combined VKORC1 1173 CT and CC genotypes varied among the four Israeli ethnic groups and was, on average, much higher in the Israeli (0.728) than in the Japanese population (0.152). For the Japanese cardiovascular surgery patients, the maintenance dose of warfarin was significantly larger in the combined VKORC1 1173 TC and CC genotype group than in the 1173 TT genotype group (3.6 +/- 0.5 mg vs 2.8 +/- 0.7 mg, respectively; p = 0.02).. The frequencies of the intron 1 VKORC1 1173 T>C SNP show significant differences between ethnic groups and are associated with warfarin dose requirements for achieving a recommended International Normalized Ratio range in Japanese cardiovascular surgery patients. This study supports the example of warfarin as an appropriate model for applying personalized medicine for anticoagulant drugs, and highlights the importance of ethnicity in pharmacogenetics.

Topics: Anticoagulants; Asian People; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Dose-Response Relationship, Drug; Ethnicity; Genotype; Humans; Introns; Japan; Jews; Mixed Function Oxygenases; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Vitamin K Epoxide Reductases; Warfarin

To review the frequency of hemorrhagic complications with sub-Tenon's anesthesia in patients on aspirin, warfarin or clopidogrel.. St. James's University Hospital, Leeds, United Kingdom.. Data were collected prospectively for patients having elective phacoemulsification under sub-Tenon's anesthesia. Seventy-five patients were on aspirin, 65 were on warfarin, and 40 were on clopidogrel. Seventy-five patients on no anticoagulants were used as the control group. No changes in the anticoagulant regimen were made prior to surgery.. No sight-threatening hemorrhagic complications were noted, and no surgery was postponed or cancelled due to an anesthesic complication. Subconjunctival hemorrhage occurred in 19% in the control group, 40% in the clopidogrel group, 35% in the warfarin group, and 21% in the aspirin group. The warfarin and clopidogrel groups had the highest incidence of subconjunctival hemorrhage (P<.05). The incidence of hemorrhages involving more than 1 quadrant was highest in these 3 groups; however, this did not achieve statistical significance (P = .37, Fisher exact test).. Data from this study support the continued use of anticoagulant agents among routine users during cataract surgery using a sub-Tenon's block.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Local; Anticoagulants; Aspirin; Cardiovascular Diseases; Cerebrovascular Disorders; Clopidogrel; Conjunctival Diseases; Connective Tissue; Eye Hemorrhage; Female; Humans; Lens Implantation, Intraocular; Male; Medical Audit; Middle Aged; Phacoemulsification; Prospective Studies; Risk Factors; Ticlopidine; Warfarin

The annual stroke rate in atrial fibrillation is around 5 per cent with increased risk in those with hypertension, diabetes, left ventricular dysfunction and other cardiovascular risk factors. This study set out to identify the patients with atrial fibrillation and modifiable risk factors for stroke.. Analysis of practice computer data taken from eight general practices (81 811 patients) in the south of England. 944 patients with a diagnosis of atrial fibrillation, of whom 782 (82.8 percent) were aged 65 years and over.. The age standardised prevalence of diagnosed atrial fibrillation was 1.23 per cent (1.28 percent for men and 1.18 percent for women). It was much more prevalent in the older population, 8.28 percent and 6.66 percent for males and females over 65, respectively. Cardiovascular co-morbidities were more frequent with increasing age. Blood pressure (BP) was recorded in over 95 per cent of patients with atrial fibrillation though there was scope for improving control; 25 per cent of men and 31 per cent women had a BP over 150/90. Inconsistent recording of ECG and echocardiography made it hard to identify patients with left ventricular dysfunction. Forty six percent of men and 37 percent of women were either being prescribed Warfarin, or had contraindications to its use; of those on Warfarin 75.9 percent have an international normalized ratio in range. Forty four per cent were treated with aspirin. People at high risk of stroke were no more likely to be treated with Warfarin or aspirin than those at moderate risk.. The rate of use of Warfarin remains low, and there is scope for better recording and management of risk factors particularly BP.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Diabetes Complications; England; Family Practice; Female; Humans; Male; Middle Aged; Prevalence; Risk Assessment; Risk Factors; Sex Distribution; Stroke; Wales; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Diseases; Clinical Trials as Topic; Comorbidity; Female; Humans; Hypertension; Incidence; Male; Quality of Life; Risk Factors; Stroke; Treatment Outcome; Warfarin

Warfarin, a commonly prescribed anticoagulant, exhibited large inter-individual and inter-ethnic differences in the dose required for its anticoagulation effect. Asian populations, including Chinese, require a much lower maintenance dose than Caucasians, for which the mechanisms still remain unknown. We determined DNA sequence variants in CYP2C9 and VKORC1 in 16 Chinese patients having warfarin sensitivity (< or = 1.5 mg/day, n = 11) or resistance (> or = 6.0 mg/day, n = 5), 104 randomly selected Chinese patients receiving warfarin, 95 normal Chinese controls and 92 normal Caucasians. We identified three CYP2C9 variants, CYP2C9*3, T299A and P382L, in four warfarin-sensitive patients. A novel VKORC1 promoter polymorphism (-1639 G > A) presented in the homozygous form (genotype AA) was found in all warfarin-sensitive patients. The resistant patients were either AG or GG. Among the 104 randomly selected Chinese patients receiving warfarin, AA genotype also had lower dose than the AG/GG genotype (P < 0.0001). Frequencies of AA, AG and GG genotypes were comparable in Chinese patients receiving warfarin (79.7, 17.6 and 2.7%) and normal Chinese controls (82, 18 and 0%), but differed significantly from Caucasians (14, 47 and 39%) (P < 0.0001). The promoter polymorphism abolished the E-box consensus sequences and dual luciferase assay revealed that VOKRC1 promoter with the G allele had a 44% increase of activity when compared with the A allele. The differences in allele frequencies of A/G allele and its levels of VKORC1 promoter activity may underscore the inter-individual differences in warfarin dosage as well as inter-ethnic differences between Chinese and Caucasians.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Asian People; Cardiovascular Diseases; Cytochrome P-450 CYP2C9; Drug Resistance; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Vitamin K Epoxide Reductases; Warfarin; White People

Multiple factors can affect the anticoagulation effect of warfarin. The objective of this study was to determine the relationship between different clinical factors and outcomes of warfarin therapy in Hong Kong Chinese patients.. The study was conducted at the anticoagulation clinic of the Prince of Wales Hospital from 1 April to 31 December 2003. Clinical data collected included demographics, indications of warfarin, dietary vitamin K consumption, and drug-drug interactions. Blood samples were obtained for the genetic polymorphism analysis of CYP 2 C 9. Linear and multiple regression analysis were used for statistical analysis to determine the correlation between variables and the importance of various factors as the determinants of warfarin dosage requirement.. A total of 63 patients were recruited. The mean warfarin dosage was 3.30+/-2.23 mg/day. The warfarin dosage ranged from 0.75 to 12 mg/day. The mean age was 59+/-14 years old. Age, dietary vitamin K consumption, chronic heart failure, atrial fibrillation, hypertension, smoking and drinking status were found to be factors statistically significant affecting warfarin dosage. We detected no single nucleotide polymorphism in CYP 2 C 9 exon 4.. Age, dietary vitamin K consumption, warfarin indication for atrial fibrillation, co-morbid with CHF, smoking and drinking status were found to be the factors that affected the warfarin requirement in Hong Kong Chinese patients. However, the genetic polymorphism in exon 4 of CYP 2 C 9 may not be associated with the warfarin sensitivity in this patient population.

Topics: Adult; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Asian People; Cardiovascular Diseases; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Exons; Female; Hong Kong; Humans; International Normalized Ratio; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Regression Analysis; Retrospective Studies; Warfarin

Warfarin and aspirin are commonly used to prevent cardiovascular diseases. Aspirin was recently found to have chemopreventive effects on colon cancer and polyps by inhibiting cyclooxygenase-2. Therefore, we evaluated whether the symptoms of bleeding related with aspirin or warfarin could be a clue in early detection of colon cancer. We also assessed the effect of aspirin on the development of synchronous polyps.. A total of forty-one and 16 patients diagnosed as colon cancer, taking aspirin or warfarin respectively were enrolled. In addition, 171 patients with colon cancers were age and gender matched as a control group. We investigated the difference of clinical features and laboratory findings among three groups.. The incidence of bleeding was 81.3% (warfarin), 53.7% (aspirin), 40.4% (control). Among three groups, location and size of cancer, number of lymph nodes involvement and stages were not different, but the number of patients in Duke stage D in warfarin group (n=1, 6.3%) were less than that of the control (n=44, 25.7%) (p=0.049). The extent of circumferential involvement by cancer was lower in aspirin group (67%) than in the control group (80%) (p=0.035). The percentage of patients with synchronous polyps and mean number of synchronous polyps in aspirin group (34.1%, 0.68, respectively) was lower than that of control group (53.6%, 1.69, respectively) (p=0.029, 0.008, respectively).. Bleeding related with aspirin or warfarin usage had no effect on the early diagnosis of colon cancer. However, lower incidence of Duke stage D in warfarin group might be related to anti-metastatic effect of warfarin. In addition, aspirin may have a role in suppressing the development of synchronous polyps.

Topics: Aged; Anticoagulants; Aspirin; Cardiovascular Diseases; Colonic Neoplasms; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Azetidines; Benzylamines; Cardiovascular Diseases; Drug Interactions; Family Practice; Heparin; Humans; Practice Guidelines as Topic; Warfarin

We reviewed 22 patients who had undergone either carpal tunnel decompression or release of Dupuytren's contractures while anticoagulated with warfarin. All patients continued with their usual anticoagulant regime over the period of operation, provided that the international normalized ratio (INR) was 3 or less. There was no abnormal intraoperative or postoperative bleeding in any patient. Journal of Hand Surgery (British and European volume, 2004).

Topics: Anticoagulants; Cardiovascular Diseases; Carpal Tunnel Syndrome; Cerebrovascular Disorders; Dupuytren Contracture; Heart Valve Prosthesis; Humans; International Normalized Ratio; Outcome Assessment, Health Care; Warfarin

Substitution of generic warfarin initially was discouraged because of concerns regarding therapeutic failure or toxicity. Although subsequent research with AB-rated (i.e., bioequivalent) warfarin did not confirm initial concerns, the issue is not settled for all clinicians.. We sought to provide additional information regarding the clinical and economic impact of warfarin conversion by analyzing a real-life sample of patients receiving long-term anticoagulation therapy who were switched from brand name to generic warfarin.. Patients who had been taking warfarin for at least 180 days and had received uninterrupted oral anticoagulation 90 days before and 90 days after switching to generic warfarin were included. The switch date was based on the first time generic warfarin was dispensed from our pharmacies. The primary end point was the calculated amount of time each patient's international normalized ratio (INR) values were within the patient-specific target INR range in the 90 days before and after the switch. Data regarding adverse events and medical resource utilization were also collected. Pharmacoeconomic analyses were performed.. The analysis included 2299 patients. The overall difference in calculated time INR values were below (22.6% before vs 26.1% after switch, p<0.0001) and within (65.9% before vs 63.3% after switch, p=0.0002) the therapeutic INR range was statistically but not clinically significant. Only 28.0% of patients experienced a change in therapeutic INR control of 10% or less, 33.1% experienced INR control that improved by greater than 10%, and 38.9% experienced INR control that worsened by more than 10%. The difference in total treatment costs associated with brand name and generic warfarin was 3128 dollars/100 patient-years in favor of the generic product. Sensitivity analyses revealed that cost savings associated with warfarin conversion in this health care system were highly dependent on the difference between warfarin costs and cost of treating anticoagulation-related adverse events.. Most of these patients were successfully switched from brand name to generic warfarin. However, supplemental INR monitoring is warranted when one warfarin product is substituted for another to allow timely detection of those patients who experience significant changes in anticoagulation response.

Topics: Aged; Cardiovascular Diseases; Colorado; Drugs, Generic; Economics, Pharmaceutical; Female; Health Maintenance Organizations; Humans; International Normalized Ratio; Male; Retrospective Studies; Warfarin

Topics: Age Factors; American Heart Association; Anticoagulants; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Practice Guidelines as Topic; Pregnancy; Societies, Medical; United States; Warfarin

Patients receiving warfarin therapy are discouraged from taking herbal medicines. Whether patients adhere to this advice and, if they do not, the types of products they use, are not known.. The objective of this observational study was to estimate the magnitude of use of herbal medicines among Chinese patients attending the Warfarin Clinic of the Prince of Wales Hospital in Hong Kong.. A medical officer interviewed all patients who attended the Warfarin Clinic during May 2001. Patients were asked about the use of herbal medicines in the preceding week. Demographic data, indication and duration of warfarin therapy, and International Normalised Ratio (INR) value at the time of the visit were also noted.. Of 107 patients interviewed, 28 (26%) claimed to have taken herbal medicines during the week prior to the clinic visit. The users of herbal medicines had lower INR values than non-users (mean INR value 2.41 +/- 0.65 vs 2.75 +/- 0.65, p = 0.019), possibly because of a lower warfarin dosage (mean dosage 2.93 mg/day +/- 1.23 vs 3.34 mg/day +/- 1.45; p = 0.185) and because a smaller proportion of such patients had heart valve replacement (21% vs 39%, p = 0.141). 'Herbal soup' (soup made at home from vegetables, meat and certain herbs for consumption with the main meals) and 'cool tea' (herbal decoction for the treatment of 'endogenous heat') were the most popular and were taken by 12 (11%) and 11 (10%) patients, respectively. Four patients took proprietary medicines each containing between one and three different herbs that could potentially enhance or antagonise the effects of warfarin. None of the patients in this study showed any evidence of thromboembolism or bleeding on the day of clinic visit.. Among Chinese patients treated with warfarin at a Hong Kong clinic, the use of herbal medicines was relatively common. Healthcare professionals play an important role in educating the patients and updating the list of herbal medicines that should be avoided by patients taking warfarin.

Topics: Blood Coagulation; Cardiovascular Diseases; Contraindications; Drug Interactions; Drugs, Chinese Herbal; Female; Humans; International Normalized Ratio; Male; Middle Aged; Patient Education as Topic; Surveys and Questionnaires; Warfarin

To evaluate the potential bleeding risks of arthrocentesis in patients with different arthropathies and taking oral anticoagulants.. Fifteen consecutive patients, 8 males and 7 females, treated with anticoagulant therapy for atrial fibrillation (9 pts), deep venous thrombosis (4 pts) and replacement of cardiac valves (3 pts) were submitted to arthrocentesis for synovial fluid effusion due to different arthropathies. In all patients INR was

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthritis; Cardiovascular Diseases; Female; Hemarthrosis; Humans; Knee Joint; Male; Middle Aged; Paracentesis; Risk Assessment; Warfarin

Some patients are driven to complementary and alternative medicine because traditional medicine offers no cure. Patients and some physicians may be unaware of potential contraindications. Bleeding is one of the primary concerns in patients using both modalities.

Topics: Cardiovascular Diseases; Complementary Therapies; Drug Interactions; Humans; United States; Warfarin

Atrial fibrillation (AF) is associated with hemostatic abnormalities and increased risk of thrombotic cardiovascular events even during oral anticoagulant therapy (OAT). The aim of our study was to evaluate the predictive value of hemostatic markers for the risk of major cardiovascular events during OAT. The study group comprised 113 patients with chronic AF (70.2 +/- 5.4 years old, 60% men), referred for OAT. Established clinical risk factors and levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) antigen and activity, before and during OAT (after 3.9 +/- 0.7 months; INR 2.57 +/- 0.57) were determined. In all patients OAT significantly suppressed levels of F1+2 by 67%,TAT by 30% and D-dimer by 48% (all p <0.001). During an average follow-up of 44 months 22/111 (20%) patients suffered a combined cardiovascular event (stroke, myocardial infarction, peripheral vascular occlusion or vascular death). Patients with cardiovascular events were significantly older, had more frequent heart failure/systolic dysfunction and had significantly increased levels of D-dimer at entry (63 vs 39 ng/mL, p = 0.005) and during OAT (33 vs 18 ng/mL, p = 0.002), and of t-PA antigen at entry (14.3 vs 10.9 ng/mL, p = 0.02) and during OAT (15.0 vs 11.2 ng/mL, p = 0.05) (all values are medians). In multivariate Cox proportional hazard models, heart failure/systolic dysfunction (hazard ratio 2.91; 95% CI 1.17-7.26; p = 0.02), high levels of D-dimer on OAT (top vs. lower two quartiles) (hazard ratio 4.78, 95% CI 1.39-16.41; p = 0.01) and t-PA antigen levels (continuous variable) (hazard ratio 1.09; 95% CI 1.01-1.17; p = 0.02) were significantly associated with combined cardiovascular events. In conclusion, high levels of D-dimer and t-PA antigen during OAT are significant predictors of combined cardiovascular events in AF patients and, on this basis, could be useful additional markers of cardiovascular risk in such patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Cardiovascular Diseases; Chronic Disease; Female; Fibrin Fibrinogen Degradation Products; Heart Failure; Hemostasis; Humans; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Tissue Plasminogen Activator; Warfarin

Polycythemia Vera (PV) and Essential Thrombocythemia (ET) are chronic myeloproliferative disorders complicated by a high incidence of thrombotic complications. Extensive coagulation studies failed to demonstrate a consistent pattern of abnormalities associated with thrombosis. Recently, a poor anticoagulant response to activated protein C (APC), due to a mutation of factor V (FV Leiden), has been identified as the most frequent hereditary disorder associated with venous thrombophilia. We investigated in 304 patients with PV and ET whether the presence of FV Leiden could be a risk factor for thrombosis. FV Leiden was found in 14/304 patients (4.6%) and was associated with venous thromboembolism (VTE) occurred before and at diagnosis (5/27,16%, with a significant difference of prevalence in comparison of that observed in asymptomatic patients, 9/263, 3%, p = 0.003). Carriership of FV Leiden was associated with VTE relapse, with a prevalence of 3.6% in asymptomatic patients, 6.9% in patients with a single episode of VTE and 18.1% in patients with recurrent VTE. The prevalence of FV Leiden in patients with and without arterial thrombosis was similar (5/79, 6% and 9/211, 4%, respectively, p = 0.337). This study indicates that the prevalence of the FV Leiden mutation in patients with PV and ET is comparable with that observed in the general population. FV Leiden mutation is a risk factor for VTE before and at time of diagnosis and for VTE recurrences. Screening for FV Leiden may be considered to identify PV and ET patients at higher risk of recurrences.

Topics: Activated Protein C Resistance; Anticoagulants; Austria; Cardiovascular Diseases; Cohort Studies; Comorbidity; Factor V; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Male; Middle Aged; Polycythemia Vera; Prevalence; Recurrence; Risk Factors; Thrombocythemia, Essential; Thrombophilia; Venous Thrombosis; Warfarin

The endothelial protein C receptor (EPCR) facilitates protein C activation and plays a protective role in the response to Escherichia coli-mediated sepsis in primates. Previously, a soluble form of EPCR (sEPCR) in human plasma was characterized, and several studies indicated that generation of sEPCR is regulated by inflammatory mediators, including thrombin-mediated up-regulation of surface metalloproteolytic activity in vitro. This study addressed the question of whether plasma sEPCR levels reflect changes in thrombin generation in patients undergoing anticoagulant treatment. The sEPCR levels in patients treated with coumarin-type oral anticoagulants were significantly lower than those in healthy asymptomatic adult volunteers (105.3 +/- 70.8 ng/mL [n = 55] versus 165.8 +/- 115.8 ng/mL [n = 200]; P <.0001). A similar decline in plasma sEPCR levels was found in patients treated with unfractionated heparin. In healthy volunteers, sEPCR levels declined to about 100 ng/mL within 3 days after initiation of an 8-day period of warfarin administration and increased within 2 days after its cessation. Plasma sEPCR levels returned to pretreatment values within 1 week, and the changes in plasma sEPCR levels mirrored changes in values for international normalized ratios. A similar decline in sEPCR levels with time was observed in 7 patients beginning treatment with warfarin for a thrombotic disorder. Prothrombin fragment 1 + 2 levels also decreased in volunteers and patients given warfarin. These results show that plasma sEPCR levels decline in response to treatment with anticoagulants whose mechanism of action is known to decrease in vivo thrombin production.

Topics: Adult; Aged; Anticoagulants; Biomarkers; Blood Coagulation Factors; Cardiovascular Diseases; Endothelium, Vascular; Enzyme Activation; Female; France; Genetic Variation; Heparin; Humans; Italy; Male; Metalloendopeptidases; Models, Biological; Peptide Fragments; Protein C; Prothrombin; Receptors, Cell Surface; Solubility; Thrombin; Thrombophilia; Vitamin K; Warfarin

Although sex differences in coronary artery disease have received considerable attention, few studies have dealt with sex differences in the most common sustained cardiac arrhythmia, atrial fibrillation (AF). Differences in presentation and clinical course may dictate different approaches to detection and management. We sought to examine sex-related differences in presentation, treatment, and outcome in patients presenting with new-onset AF.. The Canadian Registry of Atrial Fibrillation (CARAF) enrolled subjects at the time of first ECG-confirmed diagnosis of AF. Participants were followed at 3 months, at 1 year, and annually thereafter. Treatment was at the discretion of the patients' physicians and was not directed by CARAF investigators. Baseline and follow-up data collection included a detailed medical history, clinical, ECG, and echocardiographic measures, medication history, and therapeutic interventions. Three hundred thirty-nine women and 560 men were followed for 4.14+/-1.39 years. Compared with men, women were older at the time of presentation, more likely to seek medical advice because of symptoms, and experienced significantly higher heart rates during AF. Compared with older men, older women were half as likely to receive warfarin and twice as likely to receive acetylsalicylic acid. Compared with men on warfarin, women on warfarin were 3.35 times more likely to experience a major bleed.. Anticoagulants are underused in older women with AF relative to older men with AF, despite comparable risk profiles. Women receiving warfarin have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

Topics: Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Cohort Studies; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Registries; Sex Factors; Stroke; Survival Rate; Treatment Outcome; Warfarin

This article continues a series of reports updating recent research developments of particular interest to personnel involved in the treatment and management of patients with heart failure. This is a summary of selected presentations made at the Scientific Sessions of the XXIII Annual Congress of the European Society of Cardiology. Summaries of the following clinical studies are included: WARIS-II, ESCAMI, PAFAC, RITZ-I and TIME.

Topics: Anticoagulants; Aspirin; Cardiovascular Diseases; Clinical Trials, Phase II as Topic; Electric Countershock; Europe; Guanidines; Humans; Pyridines; Randomized Controlled Trials as Topic; Sulfones; Tetrazoles; Vasodilator Agents; Warfarin

Brief reversal of oral anticoagulant therapy is frequently necessary prior to minor surgery or invasive procedures. We sought to determine the effect of an oral dose of 2.0 mg of vitamin K(1) on the international normalized ratio (INR) among patients with a stable therapeutic INR who were maintained on their daily dose of warfarin. We prospectively studied a convenience cohort of patients attending an anticoagulation clinic who had either just completed treatment for venous thromboembolism or were receiving prophylaxis for atrial fibrillation, cardiomyopathy, or peripheral vascular disease. Each patient received an oral dose of 2.0 mg of aqueous vitamin K(1). Serial INR measurements were taken over 1 week. There was wide variation in the INR response between patients, from no change to complete reversal of anticoagulation. The effect also varied widely over time. There was a significant inverse correlation between the fall in logarithm of the INR and the daily warfarin dose required to achieve an INR value of 2.5 (r=-0.52, p=0.011). Use of a 2.0 mg oral dose of vitamin K(1) does not reliably reverse (correct) a therapeutic INR in patients maintained on their daily dose of warfarin.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Time Factors; Vitamin K; Warfarin

The use of pharmacogenomics to individualize drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide cost-effective pharmaceutical care. However, the combinations of disease, drug, and genetic test characteristics that will provide clinically useful and economically feasible therapeutic interventions have not been clearly elucidated. The purpose of this paper was to develop a framework for evaluating the potential cost-effectiveness of pharmacogenomic strategies that will help scientists better understand the strategic implications of their research, assist in the design of clinical trials, and provide a guide for health care providers making reimbursement decisions. We reviewed concepts of cost-effectiveness analysis and pharmacogenomics and identified 5 primary characteristics that will enhance the cost-effectiveness of pharmacogenomics: 1) there are severe clinical or economic consequence that are avoided through the use of pharmacogenomics, 2) monitoring drug response using current methods is difficult, 3) a well-established association between genotype and clinical phenotype exists, 4) there is a rapid and relatively inexpensive genetic test, and 5) the variant gene is relatively common. We used this framework to evaluate several examples of pharmacogenomics. We found that pharmacogenomics offers great potential to improve patients' health in a cost-effective manner. However, pharmacogenomics will not be applied to all currently marketed drugs, and careful evaluations are needed on a case-by-case basis before investing resources in research and development of pharmacogenomic-based therapeutics and making reimbursement decisions.

Topics: Anticholesteremic Agents; Anticoagulants; Antimetabolites, Antineoplastic; Cardiovascular Diseases; Carrier Proteins; Child; Cholesterol Ester Transfer Proteins; Cost-Benefit Analysis; Drug Therapy; Genotype; Glycoproteins; Hepatitis C; Humans; Interferons; Mercaptopurine; Methyltransferases; Pharmacogenetics; Pharmacology, Clinical; Phenotype; Pravastatin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Ribavirin; Warfarin

The accuracy of a new, portable INR monitor (CoaguChek, Boehringer-Mannheim, Indianapolis, IN) was evaluated by comparing INR results from the portable monitor with results obtained by a laboratory-based method. Dual INR measurements (portable monitor, laboratory) were performed in 163 consecutive outpatients receiving warfarin. Agreement in dual INR measurements was defined based on clinically-relevant expanded and narrow criteria and statistical criteria. Agreement in dual INR measurements also was evaluated as a function of increasing INR. The proportion of dual INR measurements that satisfied the clinically-relevant expanded, and narrow agreement criteria was 90%, and 86%, respectively. Seventy-nine percent of all dual measurements were within 0.5 INR units. The accuracy of the portable monitor was greatest for INR values less than 3.0; above this INR level, the portable monitor underestimated laboratory INR values. The proportion of dual INR measurements within 0.5 INR units for laboratory INR ranges of <2.0, 2.0-3.0, 3.1-4.0, and >4.0 was 98%, 87%, 57%, and 21%, respectively. We conclude that the portable INR monitor achieved a clinically acceptable level of accuracy when compared to the traditional laboratory method and provides a suitable alternative method of monitoring the INR in patients receiving warfarin.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Tests; Cardiovascular Diseases; Evaluation Studies as Topic; Female; Hemorrhage; Humans; Male; Middle Aged; Reference Standards; Thromboembolism; Warfarin

To determine the incidence and nature of hemorrhagic complications in patients having phacoemulsification and foldable intraocular lens (IOL) implantation while taking aspirin or warfarin.. The Jules Stein Eye Institute, University of California at Los Angeles School of Medicine, Los Angeles, California, USA.. This retrospective study reviewed the charts from the practice of 1 ophthalmic surgeon. The type of medication, dosage, indication for anticoagulant therapy, type of incision, type of anesthesia, and intraoperative and postoperative hemorrhagic complications were recorded.. Sixty-two patients (82 eyes) taking aspirin and 25 patients (31 eyes) taking warfarin were identified. Seven eyes in the aspirin group (8.5%) and 3 in the warfarin group (9.7%) experienced subconjunctival hemorrhages. Eight of the 10 subconjunctival hemorrhages occurred in eyes with scleral incisions. The remaining 2 occurred in eyes with corneal incisions. No eye developed lid ecchymosis, retrobulbar hemorrhage, hyphema, or suprachoroidal hemorrhage.. Phacoemulsification with foldable IOL implantation was performed safely in patients taking aspirin or warfarin. Subconjunctival hemorrhage was the most common hemorrhagic complication.

Topics: Anticoagulants; Aspirin; Cardiovascular Diseases; Cerebrovascular Disorders; Conjunctival Diseases; Eye Hemorrhage; Humans; Lens Implantation, Intraocular; Phacoemulsification; Retrospective Studies; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Dental Care for Chronically Ill; Drug Interactions; Humans; Patient Care Planning; Warfarin

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiology; Cardiovascular Diseases; Catheterization, Swan-Ganz; Hirudin Therapy; Humans; Myocardial Infarction; Outcome Assessment, Health Care; Warfarin

Minimizing the risk of bleeding as well as the risk of thromboembolism in dental patients being treated with anticoagulants is a common challenge for practitioners. This article features tips on evaluating and managing these patients.

Topics: Adult; Aged; Anticoagulants; Cardiovascular Diseases; Dental Care for Chronically Ill; Female; Heart Valve Prosthesis; Humans; Male; Patient Care Planning; Warfarin

Recent years have seen an increase in the use of warfarin therapy to treat patients with atrial fibrillation and mechanical heart valves. Cardiovascular Home Care in Fort Worth, Texas, developed an in-home oral anticoagulation therapy program to improve patient outcomes, prevent adverse effects of therapy, and reduce cost and resource utilization.

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Cost Control; Drug Monitoring; Forms and Records Control; Home Care Services; Humans; Inservice Training; Organizational Case Studies; Point-of-Care Systems; Texas; Treatment Outcome; Warfarin

Since 1992, we have been performing VLAP using a right-angle laser delivery system (Urolase) for BPH patients with significant underlying nonurological diseases such as diabetes mellitus, cardiovascular, pulmonary, and malignant diseases. Sufficient clinical results have been obtained without major complications during short-term and long-term observation. In this study, we discuss the clinical advantages and safety of VLAP, compared with TURP, through analysis of the clinical procedure for VLAP for patients treated with anticoagulant agents such as warfarin. In our study of 40 patients, 8 patients were treated with anticoagulants for cardiovascular disease. During the procedure and after the operation, no significant complications were encountered except for transient postoperative bleeding. The 8 patients who received simultaneous anticoagulant therapy also underwent TURP to draw a comparison. The time taken for the procedure and the volume of the blood loss were significantly reduced by VLAP. The hemostatic nature of YAG laser energy seems to result in a technical improvement over conventional I URP for patients undergoing anticoagulant therapy.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Follow-Up Studies; Humans; Laser Therapy; Male; Postoperative Complications; Prostatic Hyperplasia; Transurethral Resection of Prostate; Treatment Outcome; Warfarin

The World Health Organization (WHO), the International Committee for Thrombosis and Hemostasis, and the International Committee for Standardization in Hematology, have strongly suggested that INR (International Normalized Ratio) values should be used to report a patient's level of coagulation. This paper discusses the use of the INR to monitor a patient's coagulation level, and reviews the recommendations on the INR levels at which dental extractions and similar oral surgical procedures may be performed safely. Studies are needed to determine whether new local hemostatic agents are sufficient for the safe management of patients at higher INR levels, thereby avoiding the need for hospitalization and heparin therapy.

Topics: Anticoagulants; Cardiovascular Diseases; Dental Care for Chronically Ill; Drug Monitoring; Humans; Oral Hemorrhage; Prothrombin Time; Reference Values; Sensitivity and Specificity; Thromboplastin; Warfarin

To determine whether low-dose aspirin or warfarin induces fecal occult blood loss.. A prospective, cross-over study, of 100 participants over 40 years of age in 1 of 3 groups, taking: (1) no aspirin or warfarin, (2) daily aspirin (either 81 or 325 mg), or (3) warfarin, but no aspirin. Stool samples were collected and analyzed for the presence of occult blood using HemoQuant and Hemoccult II. After collection of baseline samples, patients initially taking no aspirin (group 1) were asked to take regular aspirin (325 mg daily) for 2 months. Patients initially taking aspirin 81 mg daily (group 2) were switched to 325 mg daily for 2 months, and vice versa.. Patients taking no aspirin had mean fecal blood of 0.68 +/- 0.05 mg hemoglobin/g stool, which increased to 1.41 +/- 0.36 mg/g after taking 325 mg of aspirin daily (P = 0.02). In contrast, patients in group 2, taking 81 mg and 325 mg of aspirin, had mean fecal blood of 0.82 +/- 0.08 mg/g (P = 0.57) and 1.04 +/- 0.23 mg/g (P = 0.13), respectively (comparisons with patients taking no aspirin). The mean blood loss in patients taking warfarin was 0.51 +/- 0.04 mg/g (P = 0.55), and fecal blood was not related to the degree of anticoagulation. There was no increase over normal in the rate of Hemoccult II-positive stool tests with aspirin or warfarin therapy.. Aspirin, but not warfarin, caused a small but clinically insignificant increase in occult fecal blood. The small blood loss in patients taking aspirin or warfarin is unlikely to interfere with fecal occult blood test. Therefore, positive fecal occult blood tests, in patients taking either low-dose aspirin or warfarin, should be managed in the same fashion as patients not taking these medications.

Topics: Analysis of Variance; Anticoagulants; Aspirin; Cardiovascular Diseases; Chronic Disease; Cross-Over Studies; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Occult Blood; Platelet Aggregation Inhibitors; Prospective Studies; Specimen Handling; Warfarin

Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics.. In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] < or = 2.8) in 71% of the patients and high (> 2.8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories.. 43% of the patients were women. Nearly three-fifths of the patients were aged 60-79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7.6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10.5 per 100 patient-years in those aged 70 or over, 6.0 in those aged under 70 (relative risk 1.75, 95% Cl 1.29-2.39, p < 0.001). The rate was also higher when the indication was peripheral and/or cerebrovascular disease than venous thromboembolism plus other indications (12.5 vs 6.0 per 100 patient-years) (1.80, 1.2-2.7, p < 0.01), and during the first 90 days of treatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p < 0.001). A fifth of the bleeding events occurred at low anticoagulation intensity (INR < 2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.0-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR > 4.5, 7.91, 5.44-11.5, p < 0.0001).. We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Italy; Male; Middle Aged; Prospective Studies; Risk Factors; Warfarin

Chinese patients are reportedly more sensitive than Caucasians to the anticoagulant effect of warfarin. We examined warfarin dose requirements and their determinants in 151 Chinese out-patients on stable maintenance dose of warfarin with international normalized ratio of 2 to 2.5. Mean daily warfarin requirement was 3.3 +/- 1.4 mg, much lower than reported doses in Caucasian patients. The most important determinant was age (r = -0.43, p < 0.001), with progressively lower warfarin requirement with increasing age (p = 0.0001). There was a weaker association with body weight (r = 0.20, p = 0.01). Patients with chronic rheumatic heart disease tended to require a smaller dose than those with heart valve replacements (2.94 +/- 1.24 vs. 3.69 +/- 1.42 mg, p < 0.01). We confirm that Chinese patients require a smaller dose of warfarin for the same degree of anticoagulation. Age is the most important factor affecting dose requirement, although body weight and underlying disease also play a role.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Asian People; Blood Coagulation Disorders; Body Weight; Cardiovascular Diseases; Drug Administration Schedule; Female; Heart Valve Prosthesis; Hong Kong; Humans; Male; Middle Aged; Rheumatic Heart Disease; Sex Factors; Thrombophlebitis; Warfarin

Optimal therapeutic ranges for an oral anticoagulant therapy has been discussed for many years. Prothrombin time, prothrombin time ratios (PTR) and thrombotest have been employed so far, but, recently, International Normalized Ratio of prothrombin time (PT-INR or INR) has been introduced. We investigated paying special interest to INR, the effectiveness of oral anticoagulant therapy in 170 prosthetic valve patients and in 157 patients with various cardiovascular diseases who received warfarin at two different centers. The thrombotest, prothrombin time and INR were measured at follow-up visits every month. Regarding the 170 patients with prosthetic valves with a mean follow-up period of 2.44 years, 9 thromboembolisms (TE) were reported. The average TT and INR values in TE-free patients among 101 in whom coagulability could be measured, were 21.1% and 1.73 respectively. The average TT and INR values in 5 patients with TE were 26.4% and 1.53 respectively and this was significantly (p < 0.01) higher (smaller) than in TE-free patients. 157 patients (mean age 55 +/- 12 y.o.) with various cardiovascular diseases (Table 2) were followed up for a mean of 4.9 +/- 3.2 years. As is seen in figure 4, mean INR values in TE patients were 1.28, in patients with bleeding complications 4.1, and in event free patients 2.07 respectively. In conclusion, with INR greater than 2.75, no thromboembolic complication occurred, but several hemorrhagic complications occurred at INR greater than 3. Therefore INR therapeutic ranges between 2.0-3.0 are recommendable both for the prevention of TE and bleeding complications.

Topics: Administration, Oral; Adult; Aged; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Prothrombin Time; Reference Standards; Thromboembolism; Warfarin

To assess the degree of haemostatic system activation, plasma levels of prothrombin fragment 1 + 2 (F1 + 2), a direct indicator for thrombin generation in vivo, were measured in 49 patients with thrombotic disease undergoing long-term warfarin therapy (Thrombotest values < or = 40%). In these patients, vitamin K dependent coagulation factors (factors II, VII, IX and X) were decreased together with the anticoagulant proteins C and S, but the mean plasma concentration of F1 + 2 was significantly decreased compared with 48 healthy subjects. In warfarin-treated patients, F1 + 2 was positively correlated with the Thrombotest value, factors II, VII, IX and X. When analysed according to the intensity of anticoagulation, patients with Thrombotest values less than 30% showed a significant decrease in F1 + 2, but the mean F1 + 2 level was normal in patients with Thrombotests higher than 30%. These findings indicate that long-term oral anticoagulant therapy suppresses thrombin generation approximately in parallel to the decrease in coagulation factors, and levels of F1 + 2 lower than healthy subjects are observed when Thrombotest values are less than 30%.

Topics: Administration, Oral; Blood Coagulation Factors; Cardiovascular Diseases; Humans; Peptide Fragments; Prothrombin; Thrombin; Warfarin

The study included 80 patients treated for sudden deafness over the last 5-7 years. Case history, laboratory findings, pure-tone audiogram and electronystagmography (ENG) findings were noted. If any abnormalities had been recorded in ENG studies, the studies were redone. ORL status was redefined and audiograms were obtained in all patients. When becoming ill, the 80 patients had not differed from the normal population in common cardiovascular risk factors. None of them had had signs of viral infection (paired serum samples had been taken at 2-week intervals; routine examinations had been done for common viral antigens). As many as 31 of the 80 patients with acute hearing loss had had abnormalities such as spontaneous nystagmus (PN), hypoexcitability (HE) and directional preponderance (DP) in the bithermal caloric tests (+44 degrees C, + 30 degrees C) of their ENG studies. Twenty of the 31 patients still had abnormal ENG studies after 5-7 years. Only 1 subject had positional nystagmus, and none had subjective vertigo. Patients with an abnormal ENG study showed a poor recovery of the speech reception threshold, whereas those with a normal ENG study showed slightly significant (p less than 0.05) recovery.

Topics: Administration, Oral; Adult; Betahistine; Cardiovascular Diseases; Cochlear Diseases; Drug Therapy, Combination; Electronystagmography; Female; Follow-Up Studies; Hearing Loss, Sudden; Heparin; Humans; Infusions, Intravenous; Male; Middle Aged; Risk Factors; Vestibular Diseases; Virus Diseases; Warfarin

Routine blood coagulation tests were performed on 431 consecutive patients enrolled in a study of the role of anticoagulation in cancer treatment (VA Cooperative Study #75). Two hundred sixteen control patients were treated with standard therapy, and 215 patients were treated with standard therapy plus sodium warfarin. At the time of entry into the study, the most common abnormalities were elevated fibrinogen levels, platelet counts, and fibrinopeptide A levels. Serial studies demonstrated a steady increase in platelet count and fibrinogen levels before death. Anticoagulation lowered FPA levels but had no significant effect on fibrinogen levels, platelet counts, or euglobulin clot lysis times. An unexpected finding was a dramatic increase in fibrin split product levels after institution of anticoagulation (means +/- SEM = 42.6 +/- 116.4 vs. 2.9 +/- 7.0 mg/L in control subjects; P less than 0.02). This study supports the presence of subclinical activation of blood coagulation in most patients with cancer. Moreover, the preferential activation of fibrinolysis in anticoagulated patients suggests a role for a vitamin K-dependent factor(s) in the regulation of fibrinolysis in patients with cancer.

Topics: Blood Coagulation Tests; Cardiovascular Diseases; Fibrinogen; Fibrinopeptide A; Humans; Neoplasms; Platelet Count; Thrombin; Warfarin

The stability of factor VIII was studied in plasmas from patients on long-term warfarin therapy. The percent residual factor VIII activity (F.VIII:C) after incubation at 37 degrees C for 4 hr was higher in warfarinized patients than in normal subjects; 76.9 +/- 10.8% (mean +/- SD) of the initial F.VIII:C in the patients versus 61.6 +/- 5.8% in normal subjects (p less than 0.001). On the whole, neither protein C nor vitamin K-dependent coagulation factors except factor VII activity (F.VII:C) correlated with the residual F.VIII:C. There was a negative and weak correlation between the residual F.VIII:C at 4 hr and either the initial F.VIII:C or F.VII:C. Another experiment using protein C depleted plasma showed a relatively enhanced stability of F.VIII:C in the protein C deficiency. These results indicate that factor VIII is more stable in warfarinized plasma, and that protein C and vitamin K-dependent coagulation factors are not the sole, main factor responsible for such a phenomenon.

Topics: Blood Coagulation Factors; Cardiovascular Diseases; Drug Stability; Factor VIII; Glycoproteins; Humans; Protein C; Prothrombin; Reference Values; Vitamin K; Warfarin

An empirical protocol for dosage adjustment in warfarin therapy was evaluated by means of retrospective analysis of the medical records of 106 outpatients at an anticoagulation clinic followed from January 1981 to August 1984. There were 203 cases in which the prothrombin time was abnormal (below the therapeutic range in 123 cases and above the range in 80). The protocol was successful in about 60% of cases in which the prothrombin time before dosage adjustment was below the therapeutic range and in 80% of cases in which it was above the range. Statistical analysis showed that the success rate could be improved by more precise definition of the percentage of dosage change in certain situations. However, individual variation in response of the prothrombin time to a standard dosage change limits the success that can be expected after the initial adjustment. We propose an improved protocol for adjustment of warfarin dosage.

Topics: Adult; Animals; Cardiovascular Diseases; Cricetinae; Female; Humans; Male; Middle Aged; Prothrombin Time; Retrospective Studies; Warfarin

Three hundred and eighty-four patients were studied for up to 1 year while on continuous oral anticoagulant therapy and the quality of control of therapy was assessed. Two hundred and thirty-five patients were on continuous therapy throughout the year (long-term group), 73 were treated for a period between 3 and 12 months (intermediate group) and 76 were treated for less than 3 months (short-term group). The therapeutic objective was to achieve and maintain British Ratio (BR) between 2.0 and 4.0. Nineteen percent of the results in the long-term group, 26.6% in the intermediate group and 41.1% in the short-term group fell outside this range. Among the long-term group only 25.1% and in the intermediate group 12.3% had all their results within the control range. It is concluded that the quality of therapeutic control of oral anticoagulant therapy needs to be improved.

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Drug Therapy; Follow-Up Studies; Humans; Quality Assurance, Health Care; Time Factors; Warfarin

The tissue factor coagulant activity of peripheral blood monocytes was measured in 20 patients on long-term anticoagulant treatment with warfarin and in 21 healthy individuals. Contrary to expectations, tissue factor activity was not reduced in the warfarin-treated group and was, in fact, elevated in several patients. No relationship existed between the daily warfarin dose or the degree of prolongation of the prothrombin time and the monocyte tissue factor activity. These results indicate that monocyte tissue factor activity is not necessarily reduced to below normal levels with warfarin treatment.

Topics: Cardiovascular Diseases; Female; Humans; Male; Monocytes; Phytohemagglutinins; Prothrombin Time; Thromboplastin; Warfarin

Topics: Anesthesia, Dental; Anesthesia, General; Anesthetics, Local; Anti-Bacterial Agents; Anticoagulants; Antihypertensive Agents; Cardiovascular Diseases; Dental Care; Endocarditis, Subacute Bacterial; Heart Diseases; Humans; Medical History Taking; Mouth; Nitroglycerin; Time Factors; Vasoconstrictor Agents; Warfarin

A study of 31 patients with cardiovascular disease who were taking warfarin regularly had shown pronounced intersubject differences in serum protein binding of warfarin and a highly significant correlation between the body clearance of warfarin and the free fraction of the drug in serum. Similar observations have been made in experimental animals and are consistent with predictions based on theoretical considerations. The purpose of this investigation was to determine the intrasubject variation in the free fraction of warfarin in serum. Samples of serum were obtained from 23 of the 31 patients previously studied. The time interval between the two studies was 3.4 to 5.7 mo. The daily dose of warfarin had been changed by 10.6% on the average. With two exceptions, there was no change in concurrent medications. The ratio of free fraction values of warfarin in serum, second/first study, was 0.948 +/- 0.297 (mean +/- S.D.), and there was a highly significant correlation (P less than 0.001) between the individual free fraction values in the first and second studies.

Topics: Adult; Aged; Blood Proteins; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Protein Binding; Warfarin

The serum protein binding and elimination kinetics of warfarin were determined in 31 patients with cardiovascular disease who were taking warfarin regularly. The free fraction of warfarin in the serum ranged from 0.00436 to 0.0189, indicating 98.11% to 99.56% protein binding. There was no apparent relationship between the extent of protein binding of warfarin and the concentration of albumin or total protein in the serum. The estimated total body clearance of warfarin in the patients ranged from 1.16 to 4.35ml/hr/kg of body weight and correlated significantly with the free fraction of warfarin in serum. This correlation has been predicted on theoretical grounds and shows that serum protein binding is a major determinant of the elimination kinetics of warfarin in man and an important cause of interindividual variations in its body clearance. The interindividual variation of free warfarin concentrations in the serum of patients with similar prothrombin times was somewhat smaller than the variations in total serum-warfarin concentrations and in the daily dose of warfarin. There was no correlation between prothrombin time and the concentration of free warfarin in serum, indicating that variables other than protein binding also affect the anticoagulant response of patients.

Topics: Adult; Aged; Anticoagulants; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Protein Binding; Prothrombin Time; Warfarin

The Anticoagulation Service insures uniformity of approach to the regulation of anticoagulation for patients of hospital-based primary physicians. There has been no anticoagulant-related mortality in 254 patient treatment-years, and the major complication rate is 4% of treatment courses. There is a relatively low complication rate because of the systematic approach to anticoagulation therapy, recognition of the importance of patient education, communication with the primary physician, and flexibility of drug dosage and patient visit regimens. Achieving the therapeutic range of the prothrombin time with minimum complications is the goal of this Service. The hallmark of adequate control is predictable response of the prothrombin time to adjustments in drug dosage. Statistical analysis of six years' experience has provided support for the thesis that control of anticoagulation and incidence of complications are not significantly altered by patient age, sex, or the presence of concurrent nonthromboembolic medical illness.

Topics: Administration, Oral; Ambulatory Care; Anticoagulants; Cardiovascular Diseases; Continuity of Patient Care; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hemorrhage; Humans; Long-Term Care; Male; Maryland; Outpatient Clinics, Hospital; Postoperative Care; Prothrombin Time; Warfarin

Topics: Aged; Attitude; Cardiovascular Diseases; Evaluation Studies as Topic; Female; Hospitals, Teaching; Humans; Medication Errors; Medication Systems, Hospital; Middle Aged; North Carolina; Patients; Pharmacy Service, Hospital; Pilot Projects; Prednisone; Secobarbital; Self Medication; Warfarin

Topics: Arteriosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Angiography; Cerebrovascular Disorders; Dextrans; Hematologic Diseases; Heparin; Humans; Infarction; Injections, Intravenous; Ischemic Attack, Transient; Papaverine; Subclavian Steal Syndrome; Vertebral Artery; Warfarin

Aortic valve replacement with the University of Cape Town lenticular prosthesis was performed in 149 patients during a six-year period, almost all patients being severely disabled with advanced heart disease. There was a hospital mortality of 12 per cent. Bacterial endocarditis was a serious complication and accounted for three hospital and five long-term deaths. The survivors were followed for periods of up to 72 months (average 24), the minimum period of observation being six months. There were 23 late deaths due to heart disease, of which 5 where due to myocardial failure. Myocardial failure unrelieved or only temporarily alleviated by the operation occurred in three surviving patients. The main problems have been sudden death and systemic embolism. Some of the cases of sudden death were due to coronary artery embolism, but in a number the cause could not be determined even at necropsy, and they were presumed to be due to arrhythmia. Both complications appeared to be related to valve design. A bare steel seat was associated with a high incidence of both complications, whereas a woven Dacron-velour cloth-covered seat almost eliminated embolism and reduced the incidence of sudden death. Long-term anticoagulant therapy appears to be of no real value with the cloth-covered valve. Gratifying results were obtained in the surviving patients with loss of all symptoms in 80 per cent and improvement in almost all patients. This improvement or relief of symptoms was maintained in most patients throughout the period of study.

Topics: Adolescent; Adult; Aged; Alloys; Anemia, Hemolytic; Angina Pectoris; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Arrhythmias, Cardiac; Cardiovascular Diseases; Child; Endocarditis, Bacterial; Female; Follow-Up Studies; Heart Valve Prosthesis; Humans; Male; Middle Aged; Phenindione; Polymers; Postoperative Complications; Thromboembolism; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Dicumarol; Drug Therapy; Geriatrics; Heparin; Myocardial Infarction; Phenindione; Warfarin

Topics: Accident Prevention; Acid-Base Equilibrium; Cardiovascular Diseases; Heparin; Humans; Myocardial Infarction; Sodium; Thromboembolism; Warfarin

Topics: Adrenocorticotropic Hormone; Cardiovascular Diseases; Cortisone; Drug Therapy; Electrocardiography; Humans; Myocardial Infarction; Prednisone; Serum Sickness; Tetanus Antitoxin; Toxicology; Warfarin