The phase 3 AVERROES ( Apixaban Versus Acetylsalicylic acid to Prevent Strokes ) trial, designed to show the superiority of Apixaban over Acetylsalicylic acid ( Aspirin ) for the prevention of stroke or systemic embolism in high-risk atrial fibrillation patients unsuitable for treatment with a vitamin K antagonist [ Warfarin ( Coumadin ) ], was terminated early following a recommendation from the Data Monitoring Committee.

A predefined interim analysis had shown clear evidence of a clinically important reduction in stroke and systematic embolism and an acceptable safety profile for Apixaban compared to Acetylsalicylic acid.

AVERROES was a double-blind randomised trial which recruited 5600 patients with atrial fibrillation ( mean age 70 years ) demonstrated or expected to be unsuitable for treatment with Warfarin ( because of difficulty in controlling treatment effect, increased risk of haemorrhage, patient refusal to take Warfarin or intermediate stroke risk ). So far, Acetylsalicylic acid was the only effective treatment for stroke prevention in patients unsuitable for Warfarin.

Apixaban, a factor Xa inhibitor, has already been investigated for the prevention of deep vein thrombosis, following orthopaedic surgery, and after acute coronary syndrome, but not so far in patients with atrial fibrillation. The AVERROES trial compared the effects of Apixaban and Acetylsalicylic acid in these patients. Another trial, ARISTOTLE ( not yet completed ) is studying Apixaban against Warfarin in patients suitable for Warfarin.

The AVERROES study was performed at 520 sites worldwide and recruitment was completed in December 2009. The primary endpoint was a composite of stroke or systemic embolism, while the primary safety endpoint was major haemorrhage. Secondary and tertiary endpoints were a composite of stroke, systemic embolism, myocardial infarction or vascular death, and total death.

At the interim analysis results showed that the annual rate of stroke or systemic embolism ( the primary outcome ) was 3.9% per year on Acetylsalicylic acid and 1.7% per year on Apixaban ( HR=0.45, p<0.001 ). The rate of major haemorrhage was 1.4% per year on Acetylsalicylic acid and 1.6% per year on Apixaban ( HR=1.18, p=0.33 ). The rate of haemorrhagic stroke was 0.2% per year in both treatment groups and there was no evidence of hepatic toxicity or other major adverse events.

In conclusion, the results of AVERROES trial have shown a reduction in stroke and systemic embolism in patients treated with Apixaban and the increased risk of haemorrhage is small.

Source: European Society of Cardiology Meeting, 2010

XagenaMedicine2010


Link: Xapedia - Medical Encyclopedia