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NOAC vs. Warfarin for AF Across BMI and Body Weight
Quick Takes
- There is general consistency in the treatment effect of standard-dose (SD) NOACs versus warfarin for prevention of stroke/systemic embolic events across the spectrum of BMI and body weight (BW).
- There was an overall reduction in major bleeding with SD NOACs versus warfarin, with evidence of treatment heterogeneity such that there was an attenuation of this benefit for patients at a higher BMI or BW.
- The marked reduction in intracranial hemorrhage, which is the established primary safety benefit of SD NOACs over warfarin, was preserved across the spectrum of BMI and BW including in underweight patients (BMI <18.5 kg/m2 or BW <50 kg).
Study Questions:
What is the efficacy and safety of non–vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW)?
Methods:
The investigators analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the four pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation (AF). The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n = 598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. A Cox proportional hazards model stratified by trial to account for between-trial heterogeneity was used to examine each outcome across both BMI and BW, with interaction terms for BMI (or BW) and treatment allocation.
Results:
Among 58,464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across a BMI with an NOAC. NOACs reduced stroke/SEE overall (adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.73-0.88; p < 0.001), with a generally consistent effect across BMI (p for trend across HRs, 0.48). NOACs also reduced major bleeding overall (aHR, 0.88; 95% CI, 0.82-0.94; p < 0.001), but with attenuation of the benefit at a higher BMI (p for trend = 0.003).
The overall treatment effects of an NOAC versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death, which, although was reduced overall with an NOAC (net clinical outcome, aHR, 0.91; 95% CI, 0.87-0.95; p < 0.001; death, aHR, 0.91; 95% CI, 0.86-0.97; p = 0.003), tended to favor warfarin at a higher BMI (p for trend, 0.001 and 0.08, respectively). This finding was not explained by differences in ischemic or fatal bleeding events. All findings were qualitatively similar when analyzed across BW.
Conclusions:
The authors report that treatment effect of NOAC versus warfarin in AF is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated at a higher BMI and BW.
Perspective:
This patient-level meta-analysis found general consistency in the treatment effect of standard-dose (SD) NOACs versus warfarin for prevention of stroke/SEE across the spectrum of BMI and BW. There was an overall reduction in major bleeding with SD NOACs versus warfarin, with evidence of treatment heterogeneity such that there was an attenuation of this benefit for patients at a higher BMI or BW. Moreover, the marked reduction in intracranial hemorrhage, which is the established primary safety benefit of SD NOACs over warfarin, was preserved across the spectrum of BMI and BW including in underweight patients (BMI <18.5 kg/m2 or BW <50 kg). These data provide clinicians with a comprehensive overview of the efficacy and safety of SD NOACs relative to warfarin across the range of BMI and BW and may facilitate shared decision-making with patients about choice of anticoagulant.
Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Prevention
Keywords: Anticoagulants, Atrial Fibrillation, Body Weight
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