July 24th, 2011
APPRAISE-2 Dashes Hope of Adding Anticoagulant to Antiplatelet Therapy in ACS
The factor Xa inhibitor apixaban (under joint development by Bristol Myers Squibb and Pfizer as Eliquis) has been the subject of intense interest in recent years, showing great promise for thromboprophylaxis after surgery and for stroke prevention in AF. Some pundits now believe apixaban will become the anticoagulant of choice for the AF indication, although the basis for this is only a press release about the ARISTOTLE trial, which has not yet been presented or published. So far the only major disappointment concerning the drug has been the APPRAISE-2 trial in ACS patients, which was terminated early last November. The results of the trial have now been presented at the International Society on Thrombosis and Haemostasis Congress in Kyoto and published in the New England Journal of Medicine.
APPRAISE-2 (Apixaban for Prevention of Acute Ischemic Events–2) was a phase 3 trial comparing apixaban with placebo in patients with acute coronary syndrome (ACS) who were already receiving standard antiplatelet therapy and who had at least 2 additional risk factors for recurrent ischemic events. The trial was stopped early after 7392 patients had been enrolled (of 10,800 initially planned) due to an increase in major bleeding events among apixaban recipients.
Here are the main results of the trial, after a median follow-up of 241 days:
Primary endpoint (combined rate of cardiovascular death, MI, or ischemic stroke):
- 7.5% (279/3705) in the apixaban group versus 7.9% (293/3687) in the placebo group
- hazard ratio with apixaban:0.95 (95% CI, 0.80-1.11; P=0.51)
- 1.3% (46/3673) in the apixaban group versus 0.5% (18/3642) in the placebo group
- hazard ratio with apixaban: 2.59 (95% CI, 1.50-4.46; P=0.001)
The authors write that the results of APPRAISE-2 fail to confirm the hope derived from three phase 2 trials suggesting that oral anticoagulants when added to antiplatelet therapy in ACS patients would reduce recurrent events but would not cause a large excess of bleeding complications. The results of the trial, they write, “raise doubt about whether meaningful incremental efficacy can be achieved with an acceptable risk of bleeding by combining a long-term oral anticoagulant with both aspirin and a P2Y12-receptor antagonist in patients with coronary disease.”