As described in the SmPC, the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes) trial was designed to demonstrate the efficacy and safety of ELIQUIS versus aspirin for the prevention of stroke or systemic embolism in patients who were unsuitable for VKA therapy.
AVERROES was stopped early based on the recommendation of the trial’s independent Data Monitoring Committee due to clear evidence of reduction of stroke and systemic embolism with an acceptable safety profile. In AVERROES, ELIQUIS was statistically superior to acetyl salicylic acid (ASA) in the primary endpoint of prevention of stroke (hemorrhagic or ischemic) and systemic embolism compared to ASA (1.62% vs. 3.63%, HR=0.45; CI=0.32, 0.62, P<0.0001), as well as in the key secondary composite endpoint of stroke, systemic embolism, MI or vascular death (4.21% vs. 6.35%, HR=0.66; CI=0.53, 0.83, P = 0.003). While not significant, there was an increase in the incidence of major bleeding with ELIQUIS compared to aspirin (1.41%/year vs. 0.92%/year). The incidence of fatal bleeding (0.16%/year vs. 0.16%/year) and intracranial bleeding (0.34%/year vs. 0.35%/year) bleeding were similar in the ELIQUIS and ASA treatment groups.
The safety of ELIQUIS has been investigated in 11,886 patients in NVAF studies treated for an average total exposure of 1.7 years. In ARISTOTLE and AVERROES, 24.4% (ELIQUIS vs. warfarin) and 9.6% (ELIQUIS vs. aspirin) of the patients treated with ELIQUIS (5 mg or 2.5 mg) twice daily experienced adverse reactions. Common adverse reactions were epistaxis, contusion, haematuria, haematoma, eye haemorrhage, and gastrointestinal haemorrhage. The overall incidence of adverse reactions related to bleeding with ELIQUIS was 24.3% in the ELIQUIS vs. warfarin study and was 9.6% in the ELIQUIS vs. aspirin study. In ARISTOTLE study, the incidence of ISTH major gastrointestinal bleeds (including upper GI, lower GI, and rectal bleeding) with ELIQUIS was .76%/year. The incidence of ISTH major intraocular bleeding with ELIQUIS was 0.18%/year.