McMaster University

McMaster University

Faculty of
Health Sciences



Combination therapy benefits people with quivering heart

By Laura Thompson
Published: April 1, 2009
Dr. Stuart Connolly
Dr. Stuart Connolly, a professor of medicine at McMaster University and a cardiac electrophysiologist at Hamilton Health Sciences

Approximately 250,000 Canadians are diagnosed with atrial fibrillation, a condition that causes the upper chambers of heart to quiver and leads to an increased risk of stroke and complications of circulatory system.

Oral blood thinners, such as warfarin and aspirin, are the only proven therapies for atrial fibrillation. Research has shown that warfarin is more effective of the two, but many patients cannot take the medication for reasons that include an increased risk of bleeding.

A new study by McMaster University researchers has found that people with atrial fibrillation who are unsuitable for warfarin therapy have another alternative to reduce their risk of complications. By taking clopidogrel (Plavix) in addition to aspirin, patients are able to further decrease their risk of stroke and heart attack without facing an unreasonable risk of bleeding.

The study, known as ACTIVE A, was led by Dr. Stuart Connolly, a professor of medicine at McMaster University and a cardiac electrophysiologist at Hamilton Health Sciences. Dr. Connolly presented the findings today at the Annual Scientific Session of the American College of Cardiology.

The major conclusions of the ACTIVE A study are:

  • The addition of clopidogrel to aspirin reduces major vascular events by 11 per cent
  • This was achieved by means of a 28 per cent reduction in stroke and a 23 per cent reduction in heart attack
  • Clopidogrel increased risk of major bleeding from 1.27 per cent to 2 per cent per year

"In other words, if you treated 1,000 patients over the course of three years by adding clopidogrel to aspirin, you would prevent 28 strokes, 17 of which would be fatal or disabling, and you would prevent six heart attacks," said Dr. Connolly, an investigator at the Population Health Research Institute at McMaster. "This would occur at a cost of 20 major bleeds. These results are important and will change practice because clopidogrel plus aspirin has been shown to have an important effect against stroke at an acceptable risk of hemorrhage."

Warfarin continues to be most effective treatment against stroke in atrial fibrillation. Compared to aspirin, it reduces stroke by 38 per cent, however it increases major hemorrhage by 70 per cent and intracranial hemorrhage by more than 100 per cent. It is also difficult to use, requiring monitoring and restrictions of lifestyle. Aspirin alone is modestly effective, reducing stroke by 22 per cent.

"The addition of clopidogrel to aspirin, in many patients with atrial fibrillation who are unsuitable for warfarin, will provide an overall additional benefit on top of aspirin at a manageable risk," said Dr. Salim Yusuf, director of the Population Health Research Institute.

The study involved more than 7,500 patients with atrial fibrillation and at least one risk factor for stroke. All were treated were treated with aspirin (75-100 mg/day, recommended) and randomized to receive either clopidogrel (75 mg/day) or matching placebo. 

The study was funded by Sanofi-Aventis and Bristol-Myers Squibb but was independently conducted, analyzed and interpreted at the Population Health Research Institute.

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