A large new study found that taking aspirin with clot busting drug Plavix (clopidogrel) cut the risk of stroke by 28 per cent in patients with irregular heart rhythms (atrial fibrillation) who were not able to take anticoagulants like warfarin.
The study was the work of researchers working on the ACTIVE trial (ACTIVE stands for Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) and was led by principal investigator Dr Stuart Connolly, who is head of cardiology at McMaster University in Hamilton, Ontario, Canada.
The findings are published in the 31 March online issue of the New England Journal of Medicine, NEJM and were also presented on Tuesday at the American College of Cardiology scientific meeting in Orlando, Florida.
The main point of this part of the ACTIVE trial (called ACTIVE-A) was to investigate the effect of adding Plavix to aspirin as a way to reduce stroke risk in patients with atrial fibrillation who can’t take vitamin K-antagonists (anticoagulants, the most common one being warfarin), which are normally given with aspirin.
Involving a total of 7,554 patients, the trial showed that taking Plavix with aspirin led to an 11 per reduction in deaths and cardiovascular events, including strokes and heart attacks, compared with aspirin alone.
All the participants had atrial fibrillation, an increased risk of stroke, and were unsuited to vitamin K-antagonist (warfarin) therapy. They were randomly assigned to take either 75 mg a day of Plavix (clopidogrel) or placebo, in addition to aspirin.
The main outcome was a combined measure of stroke, myocardial infarction (heart attack), non-central nervous system systemic embolism, or death due to vascular causes.
The results showed that over a median follow up of 3.6 years:
* 832 of the Plavix group (6.8 per cent per year) experienced major vascular events.
* This compared with 924 (7.6 per cent per year) of the placebo group.
* This showed as a relative risk with Plavix of 0.89 (11 per cent reduction), with 95 per cent confidence interval [CI] ranging from 0.81 to 0.98; P=0.01.
* The difference was mainly due to a lower risk of stroke in the Plavix group.
* 296 of the Plavix group (2.4 per cent per year) experienced strokes.
* This compared with 408 (3.3 per cent) in the placebo group.
* This showed as a relative risk with Plavix of 0.72 (28 per cent reduction), with 95 per cent CI ranging from 0.62 to 0.83;P<0.001.
* 90 of the Plavix group (0.7 per cent per year) experienced myocardial infarction (heart attack).
* This compared with 115 (0.9 per cent per year) in the placebo group.
* This showed as a relative risk with Plavix of 0.78 (22 per cent reduction), with 95 per cent CI ranging from 0.59 to 1.03; P=0.08.
* 251 of the Plavix group (2.0 per cent per year) experienced major bleeding.
* This compared with 162 (1.3 per cent per year) of the placebo group.
* This showed as a relative risk with Plavix of 1.57 (57 per cent increase) with 95 per cent CI ranging from 1.29 to 1.92; P<0.001.
The researchers concluded that:
“In patients with atrial fibrillation for whom vitamin K-antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage.”
The nearly 60 per cent increase in bleeding risk is less than what might be expected for the standard warfarin therapy, said the researchers.
According to a report by Reuters, Connolly said that for a lot of patients who have atrial fibrillation and high risk of stroke but who can’t take warfarin, there was currently an unmet need, and these findings appear to show Plavix provides:
“A reasonable option for these patients that reduces the risk of stroke at an acceptable risk of hemorrhage.”