In a sub-study, presented yesterday in the Late Breaking Clinical Trial Update Session, the effects of apixaban and warfarin were compared in AF patients according to their left ventricular systolic function and heart failure (HF) status.
“Patients with LV systolic dysfunction (LVSD) were at greatest risk of an adverse fatal or non-fatal clinical outcome. Therefore, because the superiority of apixaban over warfarin was consistent across subgroups, the absolute benefit of apixaban was particularly large in patients with LVSD. Patients with HF but without LVSD - i.e. patients with HF and preserved ejection fraction (HF-PEF) - were at lower risk than those with LVSD and obtained an intermediate benefit with apixaban, compared with warfarin,” said the presenter of the study, Professor John McMurray.
In the overall Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, 18,201 patients with AF and at least one additional risk factor for SSE were randomised to apixaban 5 mg bid or warfarin (target INR 2.0 to 3.0) and followed for a median of 1.8 years. Patients were recruited from 1,034 clinical sites in 39 countries. The trial, which was presented in the Hot Line Session at the ESC Congress 2011 in Paris, showed that treatment with apixaban led to a 25% reduction in total stroke and 31% reduction in bleeding. The authors calculated that, for every 1,000 patients treated with apixaban in place of warfarin, apixaban prevented six strokes, five episodes of major bleeding and eight deaths, compared with warfarin.
Patients with AF who also have HF or LVSD are known to have worse clinical outcomes in comparison with AF patients without HF or LVSD. For the current analysis, investigators compared the rate of SSE and the composites of SSE or death, and SSE, major bleeding or death according to patients’ LV function and HF status.
- For the outcome of SSE or death from any cause, focusing on patients with LVSD, the unadjusted event rate (per 100 patient years of follow-up) was 7.76 for those receiving apixaban, versus 8.37 for those receiving warfarin.
- For patients with HF-PEF the unadjusted event rate was 5.07 for those receiving apixaban, versus 5.57 for those receiving warfarin.
- For patients with neither LVSD nor heart failure, the unadjusted event rate was 3.14 versus 3.79.
“These data show that HF-PEF and, particularly, LVSD is associated with a higher rate of adverse events. But in each patient category, risk was reduced by apixaban compared with warfarin,” said McMurray, from the University of Glasgow, Scotland. “The study shows there’s a new treatment that’s superior to the current gold standard and that treatment, apixaban, delivers substantial absolute benefits in these high risk patients. I think these agents are a real step change in the management of patients with AF.”
The additional analyses currently taking place with the ARISTOTLE data include sub-studies looking at patients with renal impairment, coronary artery disease and prior stroke.