Background: Apixaban is effective in preventing stroke in atrial fibrillation in the diverse populations enrolled in clinical trials. Less is known about how outcomes and treatment effects relate to varying levels of adherence.
Methods: Thus, we analyzed data from the ARISTOTLE trial comparing apixaban with warfarin. The population in this analysis included those who did not die or permanently discontinue study medications in the first 6 months. Patients were categorized as <80% (low), 80–90% (moderate), and >90% (high) adherent (by pill count) to apixaban or blinded placebo. Outcomes (after 6 months) include mortality, stroke or systemic embolism, myocardial infarction (MI), and major bleeding.
Results: Of the 18,201 patients randomized, adherence data were available on 17,569 (96.5%). Among these <80% adherence was seen in 1149 (6.5%), 80–90% in 1523 (8.7%), and >90% in 14,897 (84.8%). Prior vitamin K antagonist (VKA) use was associated with higher adherence to apixaban (53.4% in low vs. 58.0% in high; p=0.003). Baseline aspirin use was associated with lower adherence (35.1% in low vs. 30.3% in high; p<0.001). Compared with patients in the high adherence group, those in the low adherence group had higher all-cause mortality (HR 1.33, 95% CI 1.06–1.67) followed by the moderate adherence group (HR 1.31, 95% CI 1.07–1.62). MI (HR 1.97, 95% CI 1.16–3.35) and major bleeding (HR 1.54, 95% CI 1.13–2.11) were highest in the low adherence group followed by the moderate adherence group (HR 1.13, 95% CI 0.61–2.11) and (HR 1.43, 95% CI 1.08–1.89). However, stroke was higher in the moderate adherence group (HR 1.49, 95% CI 1.05–2.10) followed by the low adherence group (HR 1.22, 95% CI 0.79–1.87). Independent predictors of good adherence include age (OR 1.08, 95% CI 1.04–1.12; per 5 years <70 years), prior VKA use (1.15, 1.05–1.24), and CHADS2 score (1.11, 1.01–1.23; 2 vs 1).
Conclusion: Roughly 85% of patients had more than 90% adherence to apixaban/placebo. Age, prior use of VKA, and CHADS2 score were predictors of high adherence. Patients with high adherence had lower rates of mortality, MI, and major bleeding.