Strong full-study results from the ARISTOTLE trial of apixaban (Eliquis) have been revealed at the European Society of Cardiology’s annual meeting in Paris this week, meaning three new anticoagulants have now proved superior to warfarin in AF patients.
Additional data on the new drugs’ effects in patients with renal impairment and those taking concomitant treatments have also been presented at the conference.
Apixaban, a direct factor Xa inhibitor, reduced the risk of stroke or systemic embolism by 21% compared with warfarin and reduced the risk of major bleeding by 31%, the randomised, double-blind ARISTOTLE trial of more than 18,201 AF patients found.
This was similar to the findings of the RE-LY trial of the direct thrombin inhibitor, dabigatran, and the ROCKET-AF trial of the other direct factor Xa inhibitor, rivaroxaban.
The authors of the ARISTOTLE claimed in the New England Journal of Medicine this week that apixaban appeared to “combine the advantages” of dabigatran 150mg twice daily (which reduced the rate of stroke but not bleeding compared with warfarin) and dabigatran 110mg (which reduced the rate of bleeding but not stroke).
In an accompanying editorial, Dr Jessica Mega of Harvard University also noted that apixaban was the first of the newer anticoagulants to show a significant reduction in the risk of death from any cause compared with warfarin, although the other drugs also showed similar trends.
Of the three drugs, only dabigatran at a dose of 150mg held the distinction of reducing the risk of ischaemic stroke –as well as haemorrhagic stroke –compared with warfarin, she added.
Some of these differences could come down to variations in the design of the studies, she noted. For instance, RE-LY was not double-blind like ROCKET-AF and ARISTOTLE, and a higher-risk population was also enrolled in ROCKET.
Furthermore, the mean percentage of time in which INR was in the therapeutic range was 62% in ARISTOTLE, compared with 64% in RE-LY and 55% in ROCKET.
Meanwhile, a sub-analysis of the ROCKET trial has found that in AF patients with moderate renal impairment, giving a reduced dose of rivaroxaban (15mg/day compared with 20mg/day) preserved the treatment effect of warfarin, without increasing bleeding and with fewer fatal bleeds. The p-value was not significant.
And a post-hoc analysis of the RE-LY trial has found that combining P-gp inhibitors such as amiodarone and verapamil with dabigatran did not alter the overall benefits of the drug for stroke prevention, major bleeding events or ICH relative to warfarin.
Of the three new anticoagulants, dabigatran is the only that has already been approved for AF patients in Australia. It is still not PBS-listed, despite a positive recommendation by the Pharmaceutical Benefits Advisory Committee.
NEJM 2011; doi: 10.1056/NEJMoa1107039
http://www.nejm.org/doi/full/10.1056/NEJMoa1107039?query=featured_home
European Heart Journal 2011; doi: 10.1093/eurheartj/ehr342
http://eurheartj.oxfordjournals.org/content/early/2011/08/26/eurheartj.ehr342.abstract