Anti-inflammatories tied to cardiac risk

Heart attack survivors using certain painkillers are more likely to die or suffer another event

People who have survived a heart attack seem to increase their risk of having another one, or of dying, by taking common painkillers called NSAIDs, a popular class of drugs that includes ibuprofen.

The unsettling link between non-steroidal anti-inflammatory drugs and heart attack risk is not new. The American Heart Association released guidelines in 2007 discouraging the use of any NSAIDs among people with a history of cardiovascular disease. Researchers in Denmark now bolster that link with the largest study to date of NSAID use in heart patients. The findings appear September 10 in Circulation.

In conducting the analysis, the scientists mined a huge database to identify every first-time heart attack in people 30 years old or older that occurred in the country between 1997 and 2009, nearly 100,000 people in all. The researchers then cross-checked this information with death records, subsequent heart attacks and NSAID prescriptions. (Most NSAIDs in Denmark are prescribed.) About 44 percent of people were prescribed an NSAID during the five years following a first heart attack.

Compared with people who didn’t get NSAIDs via prescription, those who did were 63 percent more likely to die over the next five years and 41 percent more likely to die specifically of a heart problem or to have another heart attack.

“This is the biggest study, no question, in terms of numbers and completeness,” to address the NSAID/heart risk question, says Vibeke Strand, a rheumatologist at Stanford University School of Medicine.

While the study shows that NSAIDs as a group seem to boost heart attack risk, certain NSAIDs, such as diclofenac (Voltaren), appear worse than others. While the drug is sold by prescription only in the United States and Denmark, it is offered over the counter in other parts of Europe, says study coauthor Anne-Marie Schjerning Olsen, a physician at the University of Copenhagen. “I think it’s a huge problem,” she says.

Ibuprofen, which is marketed as Advil and Motrin, seemed to impart a consistent risk as well. The apparent risk from naproxen, sold as Aleve, was equivocal in these data, particularly after a patient had gotten past the first year post–heart attack.

Strand says the researchers have compiled “very impressive data.” But she notes that the researchers were unable to track use of aspirin, which is sold over the counter in Denmark. Daily low-dose aspirin limits heart attacks by reducing the blood’s clotting ability. “If you don’t take aspirin regularly, or if you take it simultaneously with NSAIDs, you lose that aspirin benefit,” Strand says. NSAIDs bind to the same molecular pocket on blood platelets as aspirin does, crowding out the aspirin. While NSAIDs have some ability to limit clotting caused by platelet aggregation, this capacity fades as the drugs wear off, she notes. In contrast, when aspirin binds to a platelet, its effect is irreversible, which is how daily aspirin suppresses stickiness in the population of platelets even as they are replenished.

“Some people think that if they are taking NSAIDs, they don’t need aspirin,” Strand says. “That’s absolutely wrong.” Patients who need NSAIDs for pain or inflammation, yet who have risk factors for heart disease, should take aspirin at least a few hours before taking an NSAID, she says.

Reducing aspirin’s protective effect might explain part of why NSAIDs seem to add to heart risk. NSAIDs have also been linked to increased blood pressure and atrial fibrillation, a heart rhythm disorder.

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