Extrapolating from COMMIT, Dr. Chen said that giving this simple, inexpensive, safe, and modestly effective treatment to 1 million acute MI patients would save 5,000 lives and prevent an additional 5,000 strokes or repeat MIs. There are an estimated 10 million acute MIs per year worldwide, a third of which are STEMI, he added.
Discussant Christopher P. Cannon, M.D., said CLARITY and COMMIT are complementary trials that collectively provide important information about how clopidogrel fits into the whole spectrum of STEMI therapy, since the management strategy was 100% noninvasive in COMMIT and entirely invasive in CLARITY.
There was a suggestion of slightly better outcomes with the 300-mg loading dose used in CLARITY. However, CLARITY included patients only up to age 75 years. So a rational, evidence-based approach drawn from the two trials would be to employ a loading dose of clopidogrel in STEMI patients up to age 75 who present within 24 hours of symptom onset, and to skip the loading dose in patients beyond that age, since there is good evidence of efficacy for the 75-mg dose in the very elderly from COMMIT but no safety data for a loading dose in that age group, said Dr. Cannon of Brigham and Women's Hospital, who together with Dr. Sabatine was co-principal investigator in CLARITY.
Dr. Cannon added that the worldwide public health implications of this new addition to the management of STEMI are profound. Two weeks of clopidogrel costs $50-$100, placing dual antiplatelet therapy within reach of many patients, even in some developing countries.
“The evidence provided by these two studies with 50,000 randomized patients is very, very strong,” Dr. Cannon told this newspaper. “Obviously I can't speak for the [American College of Cardiology/American Heart Association] guideline committee, but I have heard members of the committee say these studies provide about as strong evidence as you would want to add a new treatment to the guidelines for management of STEMI.”
The combination of clopidogrel and aspirin has been shown to reduce coronary risk in patients with unstable angina and in those undergoing percutaneous intervention. An ongoing study that has completed enrollment is examining whether adding long-term clopidogrel is of benefit in a broad group with high-risk vascular disease.
CLARITY was funded by Sanofi-Aventis and Bristol-Myers Squibb Co. Dr. Sabatine and Dr. Cannon have served on paid advisory boards for both companies. COMMIT was funded by those companies along with AstraZeneca, the British Heart Foundation, and the U.K. Medical Research Council.