ACTIVE A: Clopidogrel, aspirin prevented stroke in high-risk patients with AF

For patients unsuitable for warfarin treatment, clopidogrel added to aspirin may be a safer alternative.

Results of the ACTIVE A trial suggest that adding clopidogrel to aspirin therapy will reduce the risk for major vascular events in high-risk patients with atrial fibrillation who are unsuitable for vitamin K antagonist therapy.

Stuart Connolly, MD, of McMaster University, said there was an 11% risk reduction for the primary endpoint of stroke, MI, systemic embolism or vascular death with clopidogrel (Plavix, Sanofi Aventis) and aspirin.

Connolly also reported a reduction in stroke severity from 3.3% per year to 2.4% per year and a nonsignificant reduction in MI from 0.9% to 0.7% per year. There was no difference between groups in decreases of vascular death and systemic embolism.

Researchers assigned 7,554 patients with AF and at least one risk factor for stroke into ACTIVE A if they were unsuitable for warfarin.

Simultaneously, patients who could tolerate warfarin were enrolled into ACTIVE W (n=6,706). In 2006, ACTIVE W showed that adding clopidogrel to aspirin was less effective than warfarin, but the results may have been biased because all patients entering that arm of the umbrella trial, ACTIVE I, were taking warfarin at the time of enrollment. ACTIVE I will be presented later this year, Connolly said.

In ACTIVE A, all patients received 75 mg to 100 mg of aspirin daily and were randomized to receive placebo (n=3,782) or 75 mg daily of clopidogrel (n=3,772). Researchers followed 99.4% of the patients enrolled for a median of 3.6 years.

In addition to the decreases in the primary endpoints, researchers also found that clopidogrel added to aspirin did increase major hemorrhage by 58% from 1.27% per year to 2% per year.

“Consider 1,000 patients treated for three years. If you did that, you would prevent 28 strokes — 17 of which would be disabling or fatal — and six MIs at a cost of 20 major bleeds, three of which would be fatal,” Connolly said. “In addition there would be a reduction in days in hospital from about 34,000 total days down to just over 30,000 days … Overall clopidogrel provides an important benefit to many patients at an acceptable risk.” – by Judith Rusk

I’m glad to see the data from this study because they’re helpful, but I think it doesn’t mean that once clopidogrel and aspirin always clopidogrel and aspirin. In six months to a year, they might have resolved the issue that prevented that initial use of warfarin.

– Albert Waldo, MD

Cardiology Today Editorial Board member

For more information:

Connolly S. #416. Presented at: American College of Cardiology 58th Annual Scientific Sessions; March 29-31, 2009; Orlando, Fla.