Home > Uncategorized > Apixaban 5 mg BD in Patients with One Dose Reduction Criterion ( ARISTOTLE Trial)

Apixaban 5 mg BD in Patients with One Dose Reduction Criterion ( ARISTOTLE Trial)

Alexander et al report on efficacy and safety of apixaban 5 mg twice per day in patients with only one of the dose reduction criteria (age$\ge$ 80 years, body mass 1.5 mg/dL). These patients have a higher risk of ischemic events. The authors find (an analysis from the Aristotle trial) that the 5 mg twice a day was safety and efficacy compared with warfarin. The editorial is available here.

Abstract

IMPORTANCE

In the Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) trial, the standard dose of apixaban was 5mg twice daily; patients with at least 2 dose-reduction criteria—80 years or older, weight 60 kg or less, and creatinine level 1.5mg/dL or higher—received a reduced dose of apixaban of 2.5mg twice daily. Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban.

OBJECTIVE

To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria.

DESIGN, SETTING, AND PARTICIPANTS

Among 18 201 patients in the ARISTOTLE trial, 17 322 were included in this analysis. Annualized event rates of stroke or systemic embolism and major bleeding and hazard ratios (HRs) and 95%CIswere evaluated. Interactions between the effects
of apixaban vs warfarin and the presence of 1 or no dose-reduction criteria were assessed. The first patient was enrolled in the ARISTOTLE trial on December 19, 2006, and follow-up was completed on January 30, 2011. Data were analyzed from January 2015 to May 30, 2016.

MAIN OUTCOMES AND MEASURES

Analysis of major bleeding included events during study drug treatment. Analysis of stroke or systemic embolism was based on intention to treat.

RESULTS

Of the patients with 1 or no dose-reduction criteria assigned to receive the 5mg twice daily dose of apixaban or warfarin, 3966 had 1 dose-reduction criterion; these patients had higher rates of stroke or systemic embolism (HR, 1.47; 95%CI, 1.20-1.81) and major bleeding (HR, 1.89; 95%CI, 1.62-2.20) compared with those with no dose-reduction criteria (n = 13 356). The benefit of the 5mg twice daily dose of apixaban (n = 8665) compared with warfarin (n = 8657) on stroke or systemic embolism in patients with 1 dose-reduction criterion (HR, 0.94; 95%CI, 0.66-1.32) and no dose-reduction criterion (HR, 0.77; 95%CI, 0.62-0.97)were similar (P for interaction = .36). Similarly, the benefit of 5mg twice daily dose of apixaban compared withwarfarin on major bleeding in patients with 1 dose-reduction criterion (HR, 0.68; 95%CI, 0.53-0.87) and no dose-reduction criterion (HR, 0.72; 95%CI, 0.60-0.86)were similar (P for interaction = .71). Similar patternswere seen for each dose-reduction criterion and across the spectrum of age, bodyweight, creatinine level, and creatinine clearance.

CONCLUSIONS AND RELEVANCE

Patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5mg twice daily dose of apixaban vs
warfarin compared with patients without these characteristics. The 5mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion.

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