Efficacy Of Apixaban Research Articles

Apixaban reduced stroke or systemic embolism more than warfarin in AF regardless of renal function

Source Citation Hohnloser SH, Hijazi Z, Thomas L, et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2012;33:2821-30.

Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial

Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function. Baseline glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft-Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft-Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38-0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37-0.64), interaction P = 0.003]. In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.

Stroke Risk and Efficacy of Apixaban in Atrial Fibrillation Patients with Moderate Chronic Kidney Disease

Apixaban is superior to aspirin for the prevention of stroke in patients with atrial fibrillation. Apixaban is partially renally excreted and may accumulate in patients with renal impairment. We evaluated the efficacy and safety of apixaban 5 mg twice daily (2.5 mg twice daily in selected patients) compared with aspirin 81 to 324 mg daily in 1697 patients with stage III chronic kidney disease (CKD) enrolled in the Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial. Primary outcome was all stroke and non-central nervous system emboli. Compared with patients with estimated glomerular filtration rates (eGFRs) ≥60 mL/min per 1.73 m2, stage III CKD patients (n = 1697; 30% of the cohort; mean eGFR 49 mL/min per 1.73 m2) were older (mean age 75 v 68 years) with more frequent hypertension, diabetes, heart failure, and previous stroke (all P < .01). Stage III CKD was an independent predictor of primary events (hazard ratio [HR] 1.6; P = .01) and major hemorrhage (HR 2.2; P = .02). Apixaban significantly reduced primary events by 68% (5.6% per year on aspirin v 1.8% per year on apixaban; HR 0.32; 95% confidence interval [CI] 0.18-0.55; P < .001) for stage III CKD participants and by 43% (2.8% per year on aspirin v 1.6% per year on apixaban; HR 0.57; 95% CI 0.37-0.87; P = .009) for patients with eGFRs ≥60 mL/min per 1.73 m2 (P for interaction = .10). There was no significant difference in major hemorrhage in stage III CKD patients by treatment: 2.2% per year with aspirin versus 2.5% per year with apixaban (HR 1.2; 95% CI 0.65-2.1). Stage III CKD was an independent predictor of stroke in atrial fibrillation patients taking aspirin. Among stage III CKD patients, apixaban significantly reduced stroke relative to aspirin without a significant increase in major hemorrhage.

Abstract 158: Exposure to Warfarin and the Risks of Stroke and Bleeding Events among Patients with Non-Valvular Atrial Fibrillation: Real-World vs. Clinical Trial

INTRODUCTION: While recent randomized controlled trials (RCTs) have examined safety and efficacy of apixaban versus warfarin in stroke prevention among patients with nonvalvular atrial fibrillation (NVAF), real-world (RW) event rates may differ from the RCT setting. HYPOTHESIS: In a managed care, NVAF population exposure to warfarin is associated with a decreased risk of stroke and increased risk of bleed relative to non-exposure, but both stroke and bleed rates remain higher than those observed in RCT settings. METHODS: Using a retrospective cohort design, we selected patients aged ≥18 years with diagnosis of NVAF during 2007- 2009 from a Medco population of both U.S. commercial and Medicare health plans. The first claim with an AF diagnosis was defined as the study index date. Pharmacy claims were used to define periods of warfarin exposure following the study index date. Stroke and bleed events occurring during follow-up were identified using diagnosis codes on the medical claims and categorized according to occurrence during warfarin exposure or no exposure and according to patient baseline CHADS2 risk to address differences in population risk. RESULTS: Of the 37,878 patients meeting the study criteria, the mean age was 75 years (SD=8.6), and 53% were male. Among the 66% of patients with at least one prescription for warfarin, the total person-time of warfarin exposure was 41,515 years. Compared to rates occurring in two recent RCTs of warfarin exposed (ARISTOTLE) and warfarin unexposed (AVERROES; aspirin treated) patients, stroke and bleed event rates for NVAF patients in the real-world were higher overall and within each CHADS2 group. CONCLUSIONS: While in the real world warfarin use was associated with a reduction in stroke rates and an increase in bleed rates, the rate of events in real world patients relative to their RCT counterparts were higher. The absolute impact of novel agents, such as apixaban, in the real world may be greater than in RCT setting if the relative risk reductions versus alternatives from RCTs persist in the real world.

Safety and efficacy of apixaban in the treatment of atrial fibrillation.

Atrial fibrillation is a common arrhythmia that increases the risk of stroke and systemic embolism. Warfarin is a highly effective treatment in reducing this risk, but a narrow therapeutic range, drug and food interactions, required monitoring, and bleeding limit its use. We review Apixaban, an oral inhibitor of Factor Xa, which has been shown in large randomized trials to have superior efficacy in stroke reduction without an excess in bleeding events when compared with aspirin in those deemed unsuitable to receive warfarin, and demonstrates superior efficacy in reducing stroke and systemic embolism in addition to a reduction in bleeding events when compared to warfarin.

Apixaban, an Oral, Direct, Selective Factor Xa Inhibitor, in Combination With Antiplatelet Therapy After Acute Coronary Syndrome

After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding. Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone. We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.

Apixaban, an oral direct Factor Xa inhibitor: awaiting the verdict

For the last half-century, despite its many limitations warfarin has been the mainstay of treatment for patients with venous and arterial thromboembolic disease. During the past decade, a number of new oral anticoagulant agents have been developed that may offer an alternative to warfarin. Emerging data suggest that Factor Xa may be a target for inhibition. Apixaban is one such agent. It is a potent, selective, reversible, and orally bioavailable FXa inhibitor that demonstrates antithrombotic efficacy, with a favorable pharmacokinetic profile. At present, the safety and efficacy of apixaban for the prophylaxis and treatment of venous thromboembolism is being evaluated in Phase II and Phase III trials involving nearly 25,000 patients. Trials are also underway involving over 20,000 patients for secondary prevention after acute coronary syndromes and the prevention of stroke in patients with non-valvular atrial fibrillation. This review article discusses the discovery, pharmacokinetics, attributes, and current clinical trials of this emerging drug.

Promise and Problems Emerge for Oral Investigative Factor Xa Drug in Treating Acute Coronary Syndrome

Treatment with investigative apixaban, an oral factor Xa inhibitor, shows promise as add-on protection against recurrent ischemic cardiovascular events among acute coronary syndrome patients who already are on standard antiplatelet therapy, including aspirin and clopidogrel. But dose-dependent bleeding remains an unresolved problem. This article discusses the Phase 2, Placebo-Controlled, Randomized, Double-Blind, Parallel Arm, Dose-Ranging Study to Evaluate Safety and Efficacy of Apixaban in Patients with a Recent Acute Coronary Syndrome [APPRAISE-1; NCT00313300] trial.