warfarin and Peripheral-Arterial-Disease

New oral anticoagulants (NOACs) are as effective and safe as warfarin for patients with non-valvular atrial fibrillation (NVAF). Limited evidence is available regarding outcomes for NVAF patients with peripheral artery disease (PAD).. A systematic search of Medline, Embase, and the Cochrane Library was performed. Two reviewers independently performed data extraction and quality assessment using the Cochrane Collaboration tool for assessing risk of bias. All primary publications and secondary analyses comparing NOACs with other oral anticoagulation regimens for the prevention of stroke in patients with both NVAF and PAD from phase III clinical trials were evaluated. The primary outcomes were stroke, systemic embolism (SE), major bleeding, and intracranial hemorrhage (ICH), and the secondary outcomes were cardiovascular (CV) mortality, all-cause mortality, and myocardial infarction (MI).. Three articles were included in this study. The pooled results showed a relative risk for stroke/SE with NOACs of 0.86 (95% confidence interval [CI]: 0.53-1.39), for major bleeding, 1.12 (95% CI: 0.70-1.81), for ICH, 0.47 (95% CI: 0.16-1.36), for CV mortality, 0.77 (95% CI: 0.57-1.04), for all-cause mortality, 0.91 (95% CI: 0.70-1.19), and for MI, 1.10 (95% CI: 0.64-1.90).. The findings show that NOACs are effective and safe for preventing stroke/SE in patients with both NVAF and PAD.. HINTERGRUND: Neue orale Antikoagulanzien (NOAK) sind ebenso wirksam und sicher wie Warfarin für Patienten mit nichtvalvulärem Vorhofflimmern (NVAF). Hinsichtlich der Ergebnisse für NVAF-Patienten mit peripherer arterieller Verschlusskrankheit (pAVK) besteht jedoch nur begrenzt Evidenz.. In den Datenbanken Medline, Embase und der Cochrane Library wurde eine systematische Suche durchgeführt. Unabhängig extrahierten 2 Untersucher die Daten und beurteilten die Qualität anhand des Instruments der Cochrane Collaboration zur Beurteilung des Risikos für Bias. Ausgewertet wurden alle Primärpublikationen und Sekundäranalysen, in denen NOAK mit anderen Schemata unter Einsatz oraler Antikoagulanzien zur Schlaganfallprävention bei Patienten, die sowohl NVAF als auch pAVK aufwiesen, in klinischen Phase-III-Studien verglichen wurden. Die primären Endpunkte waren Schlaganfall, systemische Embolien (SE), schwere Blutungen und intrakranielle Hämorrhagien (ICH); die sekundären Endpunkte waren kardiovaskulär bedingte (CV-)Mortalität, Mortalität aus sämtlichen Ursachen und Myokardinfarkt (MI) ERGEBNISSE: In die vorliegende Studie wurden 3 Artikel einbezogen. Die gepoolten Ergebnisse zeigten ein relatives Risiko für Schlaganfall/SE unter NOAK von 0,86 (95%-Konfidenzintervall, 95%-KI: 0,53–1,39), für schwere Blutungen lag es bei 1,12 (95%-KI: 0,70–1,81), für ICH bei 0,47 (95%-KI: 0,16–1,36), für CV-Mortalität bei 0,77 (95%-KI: 0,57–1,04), für Mortalität aus sämtlichen Ursachen bei 0,91 (95%-KI: 0,70–1,19) und für MI bei 1,10 (95%-KI: 0,64–1,90).. Die vorliegenden Ergebnisse zeigen, dass NOAK zur Prävention von Schlaganfall/SE bei Patienten mit NVAF und gleichzeitiger pAVK wirksam und sicher sind.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Peripheral Arterial Disease; Stroke; Treatment Outcome; Warfarin

The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) with coronary or peripheral artery disease (CAD or PAD) remain largely unresolved. We, therefore, conducted a meta-analysis to explore the effect of NOACs compared with warfarin in these populations.We systematically searched the Cochrane Library, PubMed, and Embase databases for randomized controlled trials (RCTs) involving NOACs versus warfarin in AF patients with CAD or PAD. A random-effect model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).A total of 7 RCTs were included. In AF patients with CAD, compared with warfarin use, the use of NOACs was associated with reduced risks of stroke/systemic embolism (RR 0.82; 95% CI 0.70-0.96) and intracranial hemorrhage (RR 0.41; 95% CI 0.26-0.63), but NOACs versus warfarin showed similar risks of all-cause death (RR 0.95; 95% CI 0.86-1.05), cardiovascular death (RR 0.95; 95% CI 0.80-1.13), stroke (RR 0.80; 95% CI 0.64-1.00), myocardial infarction (RR 1.00; 95% CI 0.83-1.21), and major bleeding (RR 0.82; 95% CI 0.65-1.04). Among patients with AF and PAD, NOACs versus warfarin had similar risks for stroke (RR 0.93; 95% CI 0.61-1.42), myocardial infarction (RR 1.10; 95% CI 0.64-1.90), all-cause death (RR 0.91; 95% CI 0.70-1.19), major bleeding (RR 1.12; 95% CI 0.70-1.81), and intracranial hemorrhage (RR 0.54; 95% CI 0.16-1.85).NOACs seem to be at least as effective and safe as warfarin in AF patients with CAD. whereas NOACs versus warfarin have similar efficacy and safety in patients with PAD.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Humans; Peripheral Arterial Disease; Warfarin

The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with atrial fibrillation (AF) and peripheral artery disease (PAD) remain largely unknown. Therefore, we conducted a meta-analysis to explore the effects of NOACs versus warfarin in this population.. We systematically searched the PubMed and Embase databases, with no linguistic restrictions, until December 2019 for relevant randomized controlled trials (RCTs) and observational studies. A random-effects model using an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).. A total of six studies (three post hoc analyses of RCTs and three cohort studies) were included in this meta-analysis. Among AF patients treated with NOACs and warfarin, individuals with PAD had increased rates of all-cause death (RR = 1.26, 95% CI 1.07-1.48) and cardiovascular death (RR = 1.32, 95% CI 1.06-1.64) compared with those without PAD. In AF patients with PAD, we observed a similar risk of thromboembolic events, bleeding, and death with NOACs as with warfarin. In addition, there were no interactions between PAD and non-PAD subgroups regarding any of the reported outcomes of NOACs versus warfarin in AF patients (all P. Based on current evidence, AF patients with PAD are at a higher risk of death than those without PAD. Efficacy and safety outcomes with NOACs are comparable to those with warfarin, suggesting that the use of NOACs has effects similar to warfarin in AF patients with concomitant PAD.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Humans; Observational Studies as Topic; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Disease; DNA; Drug Therapy, Combination; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Histones; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis; Warfarin

Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

Topics: Anticoagulants; Antidotes; Coronary Artery Disease; Drug Discovery; Factor XI; Factor XII; Heart Failure; Heparin; Humans; Peripheral Arterial Disease; Stroke; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

In patients with atrial fibrillation (AF), peripheral artery disease (PAD) is associated with higher rates of stroke and bleeding. Both higher dose edoxaban (60/30 mg) and lower dose edoxaban (30/15 mg) were non-inferior to warfarin for stroke and systemic embolism (SSE) and significantly reduced major bleeding in AF patients in the global study to assess the safety and effectiveness of edoxaban vs standard practice of dosing with warfarin in patients with atrial fibrillation (ENGAGE AF-TIMI 48) trial. Whether the efficacy and safety of these dosing strategies vs. warfarin are consistent in patients with AF and PAD has not been described.. Of 21 105 patients with AF randomized to warfarin, edoxaban 60/30 mg, or edoxaban 30/15 mg, 841 were identified with PAD. Endpoints included major adverse cardiovascular events (MACEs), SSE, and major bleeding. Patients with PAD had higher risk of MACEs [adjusted hazard ratio (HRadj) 1.33, 95% confidence interval (CI) 1.12-1.57, P = 0.001] and cardiovascular (CV) death (HRadj 1.49, 95% CI 1.21-1.83, P < 0.001) than those without PAD, but not major bleeding. The efficacy of edoxaban 60/30 mg vs. warfarin was consistent regardless of PAD (SSE HR; PAD 1.16, 95% CI 0.42-3.20; no-PAD 0.86, 95% CI 0.74-1.02, P-interaction 0.57) as was major bleeding (PAD 0.96, 95% CI 0.54-1.70; no-PAD 0.80, 95% CI 0.70-0.91, P-interaction 0.54). Edoxaban 30/15 mg was inferior for SSE, with significant heterogeneity when stratified by PAD status (P-interaction 0.039).. Patients with AF and PAD are at heightened risk of MACEs and CV death vs. those without PAD. The efficacy and safety of edoxaban 60/30 mg vs. warfarin in AF are consistent regardless of PAD; however, edoxaban 30/15 mg is inferior for stroke prevention in AF patients with PAD. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00781391.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Peripheral Arterial Disease; Pyridines; Stroke; Thiazoles; Warfarin

Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm.. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037).. Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Humans; Male; Morpholines; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

To investigate the effectiveness, safety, and outcomes of lower limb events for non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin among atrial fibrillation (AF) patients with concomitant peripheral artery disease (PAD).. In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, a total of 5768 and 2034 consecutive AF patients with PAD patients taking NOACs or warfarin were identified from 1 June 2012 to 31 December 2017, respectively. We used propensity score stabilized weighting to balance covariates across study groups. In the cohort, there were 89% patients were taking low-dose NOAC (dabigatran 110 mg twice daily, rivaroxaban 10-15 mg daily, apixaban 2.5 mg twice daily, or edoxaban 30 mg daily). Non-vitamin K antagonist oral anticoagulant was associated with a comparable risk of ischaemic stroke, and a lower risk of acute myocardial infarction [hazard ratio (HR): 0.61, 95% confidence interval (CI): 0.42-0.87; P = 0.007], lower extremity thromboembolism (HR: 0.56, 95% CI: 0.44-0.72; P < 0.0001), revascularization procedure (HR: 0.58, 95% CI: 0.47-0.72; P < 0.0001), lower limb amputation (HR: 0.32, 95% CI: 0.23-0.46; P < 0.0001), and all major bleeding (HR: 0.64, 95% CI: 0.50-0.80; P = 0.0001) than warfarin after weighting. The advantage of NOACs over warfarin persisted in high-risk subgroups including patients of ≥75 years of age, diabetes, renal impairment, or use of concomitant antiplatelet agent.. This population-based study indicated that NOACs were associated with a comparable risk of ischaemic stroke, and a significantly lower risk of major adverse limb events and major bleeding than warfarin among AF patients with concomitant PAD. Therefore, thromboprophylaxis with NOACs may be considered for such patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Peripheral Arterial Disease; Warfarin

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Coronary Artery Disease; Dabigatran; Embolism; Female; Health Care Costs; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Peripheral Arterial Disease; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; United States; Warfarin

There are scarce data evaluating the effectiveness and safety of rivaroxaban vs. warfarin in non-valvular atrial fibrillation (NVAF) patients with concomitant coronary artery disease (CAD) and/or peripheral artery disease (PAD) treated in routine practice.. Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant (OAC)-naïve NVAF patients receiving rivaroxaban (15-20 mg once daily) or warfarin, with comorbid CAD and/or PAD and ≥12 months of insurance coverage before OAC initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores (standardized differences <0.1 achieved for all covariates after adjustment). Endpoints included a composite of major thrombotic vascular events (MTVEs) (including ischaemic stroke, myocardial infarction, or need for lower limb revascularization/major amputation) and major bleeding. Patients were followed until an event-of-interest, discontinuation/switch of index OAC, insurance disenrolment, or end-of-data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. We identified 3257 rivaroxaban (30.4% received a 15 mg dose) and 5046 warfarin users with NVAF and comorbid CAD and/or PAD. Rivaroxaban was associated with a 32% (95% CI = 8-50%) reduction in the composite of MTVE. No significant difference in major bleeding was observed (HR = 1.13, 95% CI = 0.84-1.52). No statistical interactions were noted in subgroup analyses performed on the MTVE (P-interaction ≥ 0.35 for all) or major bleeding endpoints (P-interaction ≥ 0.09 for all).. Among patients with NVAF and comorbid CAD and/or PAD, rivaroxaban use was associated with a reduced risk of MTVEs vs. warfarin, without significantly increasing major bleeding risk.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Coronary Artery Disease; Databases, Factual; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Thrombosis; Time Factors; Treatment Outcome; United States; Warfarin

Warfarin significantly accelerates medial arterial calcification in humans. This effect is markedly augmented in end-stage renal disease.

Topics: Aged; Anticoagulants; Breast; Case-Control Studies; Disease Progression; Female; Humans; Kidney Failure, Chronic; Mammography; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Vascular Calcification; Warfarin

Quality of warfarin therapy in patients with a mechanical prosthetic heart valve (MPHV) has been barely investigated. We analysed determinants of low time in the therapeutic range (TiTR <60%) in 2111 patients with MPHVs from the nationwide PLECTRUM study by the Italian Federation of Anticoagulation Clinics. Overall, 48·5% of patients had a TiTR of < 60%. At logistic regression analysis, arterial hypertension (odds ratio [OR] 1·502, P < 0·001), diabetes (OR 1·732, P < 0·001), heart failure (OR 1·484, P = 0·004), mitral site (vs. aortic) (OR 1·399, P = 0·006), international normalised ratio (INR) ranges of 2·5-3·5 (OR 2·575, P < 0·001) and 3·0-4·0 (OR 8·215, P < 0·001) associated with TiTR < 60%. TiTR is substantially suboptimal in MPHV patients, particularly in higher INR ranges.

Topics: Adult; Age Distribution; Aged; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Female; Heart Valve Prosthesis; Humans; Hypertension; International Normalized Ratio; Italy; Male; Middle Aged; Myocardial Ischemia; Peripheral Arterial Disease; Retrospective Studies; Smoking; Thrombophilia; Treatment Outcome; Warfarin

Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients.. In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups.. NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78-0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57-0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59-0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs.. Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.

Topics: Administration, Oral; Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Atrial Fibrillation; Databases, Factual; Diabetes Mellitus; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Lower Extremity; Male; Middle Aged; Patient Safety; Peripheral Arterial Disease; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Time Factors; Treatment Outcome; Vascular Surgical Procedures; Warfarin

We describe a patient with COVID-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. A 58-year-old man, without major comorbidity, was admitted with a 14-day history of breathlessness. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was confirmed by laboratory testing. Initial imaging revealed COVID-19 pneumonia but no pulmonary thromboembolism (PTE) on CT pulmonary angiography (CTPA). The patient subsequently developed respiratory failure and left foot ischaemia associated with a rising D-dimer. Repeat CTPA and lower limb CT angiography revealed simultaneous bilateral PTE, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. This case highlights a broad range of vascular sequalae associated with COVID-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation.

Topics: Anticoagulants; Betacoronavirus; Clinical Deterioration; Computed Tomography Angiography; Coronavirus Infections; COVID-19; Enoxaparin; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Pandemics; Peripheral Arterial Disease; Pneumonia, Viral; Pulmonary Embolism; SARS-CoV-2; Thrombosis; Treatment Outcome; 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

Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease.. Non-valvular atrial fibrillation patients aged ≥65 years diagnosed with coronary/peripheral artery disease in the US Medicare population, newly initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected from January 1, 2013 to September 30, 2015. Propensity score matching was used to compare DOACs vs warfarin. Cox proportional hazards models were used to estimate the risk of stroke/systemic embolism, major bleeding, and composite of stroke/myocardial infarction/all-cause mortality.. There were 15,527 apixaban-warfarin, 6,962 dabigatran-warfarin, and 25,903 rivaroxaban-warfarin-matched pairs, with a mean follow-up of 5-6 months. Compared with warfarin, apixaban was associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.37-0.62), major bleeding (HR 0.66; 95% CI, 0.58-0.75), and stroke/myocardial infarction/all-cause mortality (HR 0.63; 95% CI, 0.58-0.69); dabigatran and rivaroxaban were associated with lower rates of stroke/myocardial infarction/all-cause mortality (HR 0.79; 95% CI, 0.70-0.90 and HR 0.87; 95% CI, 0.81-0.92, respectively). Rivaroxaban was associated with a lower rate of stroke/systemic embolism (HR 0.72; 95% CI, 0.60-0.89) and a higher rate of major bleeding (HR 1.14; 95% CI, 1.05-1.23) vs warfarin.. All DOACs were associated with lower stroke/myocardial infarction/all-cause mortality rates compared with warfarin; differences were observed in rates of stroke/systemic embolism and major bleeding. Findings from this observational analysis provide important insights about oral anticoagulation therapy among non-valvular atrial fibrillation patients with coronary/peripheral artery disease and may help physicians in the decision-making process when treating this high-risk group of patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Medicare; Myocardial Infarction; Peripheral Arterial Disease; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin

Rivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions.. This single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ. There were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban.. Real-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65 years) but an increased risk for secondary interventions. Further studies with a larger cohort are required to validate our results.

Topics: Aged; Anticoagulants; Chi-Square Distribution; Endovascular Procedures; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Indiana; Logistic Models; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Rivaroxaban; Treatment Outcome; Vascular Surgical Procedures; Warfarin

We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD.. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had PAD at baseline. Patients with PAD had higher unadjusted rates of stroke and systemic embolism (hazard ratio [HR] 1.73, 95% CI 1.22-2.45; P=0.002) and major bleeding (HR 1.34, 95% CI 1.00-1.81; P=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (HR 1.32, 95% CI 0.93-1.88; P=0.12) and major bleeding (HR 1.03, 95% CI 0.76-1.40; P=0.83) compared with patients without PAD. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with PAD (HR 0.63, 95% CI 0.32-1.25) and without PAD (HR 0.80, 95% CI 0.66-0.96; interaction P=0.52). Patients with PAD did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (HR 1.05, 95% CI 0.69-1.58), whereas those without PAD had a statistically significant reduction (HR 0.65, 95% CI 0.58-0.73; interaction P=0.03).. Patients with PAD in ARISTOTLE had a higher crude risk of stroke or systemic embolism compared with patients without PAD that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without PAD. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and PAD.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Peripheral Arterial Disease; Proportional Hazards Models; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin

We conducted a multicenter prospective cohort study to assess the safety of warfarin therapy in Japanese hemodialysis (HD) patients.. Chronic HD patients on warfarin therapy (warfarin users) were recruited from 111 HD centers in Japan. Two dialysis-vintage-matched warfarin non-users (non-users) were selected from the same HD center as each warfarin user. Clinical data were collected upon registration and every 12 months thereafter for up to 36 months.. The final cohort consisted of 365 warfarin users and 692 non-users and was followed for an average of 27.7 months. The mean age of warfarin users (68.8 ± 10.6 years) was significantly higher than that of non-users (66.9 ± 11.0 years, p < 0.001). The analyses by multivariate Cox proportional-hazard models showed that the age [hazard ratio (HR) = 1.07 for each 1-year increase, 95 % confidence interval (CI) 1.05-1.08, p < 0.001] was significantly associated with the death from any cause, but warfarin use (1.08, CI 0.75-1.57, p = 0.68) was not when being adjusted for sex, diabetes mellitus, antiplatelet use, and atrial fibrillation. The risk of composite events, which included death from any cause, stroke, cardiovascular disease, and peripheral arterial disease, was also associated with age but was not associated with warfarin use.. The results of this study suggested that warfarin use by HD patients might not be harmful in chronic state, while the safety for the initiation of warfarin therapy in HD patients remained to be determined.

Topics: Age Factors; Aged; Anticoagulants; Calciphylaxis; Chi-Square Distribution; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Time Factors; Tokyo; Treatment Outcome; Warfarin

Matrix Gla protein is a vitamin K-dependent inhibitor of vascular calcification. Warfarin use is associated with increased breast arterial calcification, but whether this is reflective of other arteries or occurs in men is unclear. In this study, the prevalence of calcification in peripheral arteries was compared in patients with and without warfarin therapy.. This retrospective matched cohort study assessed 430 patients with radiographs performed during or after warfarin therapy who were identified by a computerized search of medical records. Each patient was matched to a patient without warfarin exposure based on age, sex, and diabetes status. Patients with warfarin exposure <1 month, history of end-stage renal disease, or serum creatinine >2.0 mg/dl were excluded. Radiographs were reviewed visually for arterial calcification. The prevalence of arterial calcification was 44% greater in patients with versus without warfarin use (30.2% versus 20.9%, P=0.0023) but not on radiographs performed before warfarin therapy (26.4% versus 22.4%, n=156) or prior to 5 years of warfarin therapy. The increase was noted only in the ankle and foot, was limited to a medial pattern of calcification, and was similar in men and women.. Warfarin use is associated with lower extremity arterial calcification in both men and women independent of age, sex, diabetes status, and other patient characteristics. This may have implications for the choice of therapies for long-term anticoagulation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Humans; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Prevalence; Republic of Korea; Retrospective Studies; Risk Assessment; Risk Factors; Vascular Calcification; Warfarin; Young Adult

Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction <40%, on warfarin response has not been evaluated. Here, we assess the influence of LVSD on warfarin dose, anticoagulation control (percent time in target range), and risk of over-anticoagulation (international normalized ratio >4) and major hemorrhage. Of the 1,354 patients included in this prospective cohort study, 214 patients (16%) had LVSD. Patients with LVSD required 11% lower warfarin dose compared with those without LVSD (p <0.001) using multivariate linear regression analyses. Using multivariate Cox proportional hazards model, patients with LVSD experienced similar levels of anticoagulation control (percent time in target range: 51% vs 53% p = 0.15), risk of over-anticoagulation (international normalized ratio >4; hazard ratio 1.01, 95% confidence interval 0.82 to 1.25; p = 0.91), and risk of major hemorrhage (hazard ratio 1.11; 95% confidence interval 0.70 to 1.74; p = 0.66). Addition of LVSD variable in the model increased the variability explained from 35% to 36% for warfarin dose prediction. In conclusion, our results demonstrate that patients with LVSD require lower doses of warfarin. Whether warfarin dosing algorithms incorporating LVSD in determining initial doses improves outcomes needs to be evaluated.

Topics: Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Ischemic Attack, Transient; Linear Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peripheral Arterial Disease; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Stroke Volume; Venous Thromboembolism; Ventricular Dysfunction, Left; Ventricular Function, Left; Warfarin

The aim of the study was to investigate the incidence and related factors of upper gastrointestinal bleeding (UGIB) in a Chinese population of peripheral arterial disease (PAD).. A total of 850 Chinese PAD patients were followed up for about 6 years. The incidence of UGIB was recorded and related factors were evaluated. A total of 749 PAD patients with complete data were included in the final statistical analysis during the median follow-up time of 69 months. The incidence of UGIB in this PAD population was 8.4% during the follow-up. Univariate analysis indicated that PAD patients with UGIB were older. A higher percentage of patients with UGIB had hypertension, CKD, history of PUD, and used aspirin or warfarin than those without UGIB. But a lower percentage of patients with UGIB used PPI. The Cox regression analysis suggested that older age (HR: 1.035, 95% CI: 1.007-1.064), comorbidities of CKD (HR: 2.410, 95% CI: 1.455-3.993), history of PUD (HR: 2.127, 95% CI: 1.102-4.100), use of aspirin (HR: 1.517, 95% CI: 1.029-2.235) or warfarin (HR: 1.576, 95% CI: 1.002-2.252) were correlated with the higher incidence of UGIB in PAD patients during follow-up. Nevertheless, PPI use (HR: 0.612, 95% CI: 0.392-0.957) was correlated with the lower incidence of UGIB.. There was a high incidence of UGIB in this Chinese population of PAD. Various factors including older age, comorbidities of CKD, history of PUD, use of aspirin or warfarin were correlated with the higher incidence of UGIB. PPI use was able to reduce the incidence of UGIB.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; China; Comorbidity; Female; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Middle Aged; Peptic Ulcer; Peripheral Arterial Disease; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Warfarin