Rivaroxaban benefits consistent in moderate CKD patients
MedWire News: The stroke-preventive effects of rivaroxaban are evident in patients with atrial fibrillation (AF) and moderate chronic kidney disease (CKD) and are not associated with an increased bleeding risk, shows a subanalysis of ROCKET AF.
ROCKET AF (Rivaroxaban Once Daily Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF) included 2950 (20.7%) patients with moderate CKD, defined as creatinine clearance of 30-49 ml/min. These patients were randomly assigned to receive rivaroxaban 15 mg/day (rather than 20/day) or warfarin.
Among patients treated according to protocol, the primary endpoint of stroke or systemic embolism occurred at a rate of 2.32 versus 2.77 per 100 patient years among patients given rivaroxaban versus warfarin, equating to a nonsignificant 6% reduction. The findings were similar in the intent-to-treat population.
The major safety endpoint, of major and clinically relevant nonmajor bleeding, occurred at similar rates in patients on rivaroxaban and warfarin, at 17.82 and 18.28 per 100 patient years, respectively. The corresponding intracranial bleeding rates were also similar, at 0.71 and 0.88 per 100 patient years.
Notably, patients assigned to rivaroxaban had fatal bleeding significantly less often than those given warfarin, at 0.28 versus 0.74 per 100 patient years, and the reduction in critical organ bleeding verged on statistical significance, at 0.76 versus 1.39 patient years (95% confidence interval 0.30-1.00).
"This study has shown that it is possible to anticoagulate patients with moderate renal dysfunction, without excessive bleeding," Keith Fox (University of Edinburgh, UK) and colleagues conclude in the European Heart Journal.
In an accompanying editorial, Stefan Hohnloser (JW Goethe University, Frankfurt, Germany) and Stuart Connolly (McMaster University, Hamilton, Canada) said: "It has been shown that the risk of bleeding associated with warfarin therapy is particularly high in patients with CKD. Hence, there is a formidable clinical dilemma in AF patients who are concomitantly suffering from renal disease."
They highlighted overall lack of increased bleeding risk with rivaroxaban versus warfarin, and that critical organ bleeding and fatal bleeds were reduced.
However, the editorialists stressed that all trials to date of warfarin alternatives have excluded patients with an estimated glomerular filtration rate of less than 30 ml/min per 1.73m2. "Accordingly, there is still a paucity of data in AF patients with more severe degrees of CKD and in those on renal replacement therapy."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Eleanor McDermid