Do Nonsmokers Benefit from Common Heart Drug?

One of the most successful drugs of all time is an anticoagulant called clopidogrel (Plavix). Since its introduction in 1998 worldwide sales of this medicine have topped $60 billion.
Plavix is prescribed to prevent blood clots that could cause heart attacks or strokes. When a stent is placed in a coronary artery to keep it open, the patient almost always gets a prescription for clopidogrel to keep the mesh tube from clogging.
Doctors have assumed that almost all patients benefit from this anticoagulant. That’s why it has been prescribed so widely. A new analysis in the Journal of the American Medical Association (June 20, 2012) throws that belief into question.
After reviewing key data, the authors conclude: “Recent analyses of large-scale trials suggest either a reduced or complete lack of clinical benefit from clopidogrel therapy in nonsmokers.” This shocking revelation suggests that a large portion of the patients currently taking clopidogrel may not be getting the expected benefit, although no one should stop taking Plavix without discussing the new research with his physician.
Just as a debit card has to activated before it can be used, clopidogrel must be converted by the body to an active compound. Smokers handle this transformation better because smoking revs the enzymes that do the work.
No doctor would ever advise a patient to smoke to get benefits from Plavix. But this isn’t the first time a popular drug has turned out to be less effective than prescribers imagined. Avandia lowered blood sugar but didn’t prevent cardiovascular complications of diabetes. If anything, it actually increased the risk for heart attacks.
Statins such as atorvastatin, lovastatin and simvastatin are widely prescribed to lower cholesterol. They are effective in reducing the risk of a second heart attack. It’s much less clear that such drugs lower a person’s chance of having an initial cardiac event (Archives of Internal Medicine, June 28, 2010).
Doctors prescribe Plavix, Avandia and statin-type cholesterol-lowering drugs with the best of intentions. They assume that the research is overwhelming that the majority of patients would benefit.
It’s jarring to learn that nonsmokers might not benefit from Plavix. The same turmoil occurred when doctors learned that Avandia did not prevent cardiovascular complications associated with diabetes and might actually have caused some.
We have no way of knowing how many people suffered side effects from medications that they took expecting (but not getting) important benefits. Plavix is known to increase the risk of hemorrhage; statins can raise blood sugar as well as cause fatigue, muscle pain and weakness; Avandia now has a warning about heart failure and heart attack.
FDA approval does not always guarantee a medicine will turn out to be safe and effective for all patients. It can take time for researchers to complete the complex studies showing exactly how well a medication works and for whom. In the meantime, as the new Plavix analysis reveals, physicians and patients must stay up-to-date on evolving drug information.