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Regular NSAID use may block heart benefits of aspirin: study of American male doctors.

Adults taking nonsteroidal anti-inflammatory drugs for pain plus aspirin to prevent heart attacks may risk losing their heart protection.

Men who took NSAIDs at least 60 days per year plus aspirin every other day had more than twice the risk of myocardial infarction as did men on the same aspirin regimen who took NSAIDs less frequently, reported Dr. Tobias Kurth of Brigham and Women's Hospital, Boston, and his colleagues.

In the 5-year Physician's Health Study, 22,071 seemingly healthy male physicians aged 40-84 years were randomly assigned to receive either 325 mg of aspirin or placebo every other day. Because both aspirin and NSAIDs inhibit the action of the isoenzyme cyclooxygenase- 1 (COX-1), the researchers performed a subanalysis of the aspirin component of the study to examine the extent to which regular NSAID use blocked the benefits of aspirin.

Confirmed MIs occurred in both groups--139 in the aspirin group and 239 in the placebo group (Circulation, 108(10):1191-95, 2003). Use of aspirin every other day plus NSAIDs for at least 60 days per year was significantly associated with MI, and aspirin appeared to have no protective benefit. But less frequent use of NSAIDs--between 1 and 59 days per year--was not associated with subsequent MIs in either the aspirin or the placebo group.

After adjustment for multiple variables including age, body mass index, exercise, history of arthritis at baseline, and smoking status, the relative risk of MI was 2.81 for the men in the aspirin group who took NSAIDs for at least 60 days a year, compared with 1.20 for those in the aspirin group who took NSAIDs 1-59 days a year. Men in the placebo group who took NSAIDs for at least 60 days a year had a relative risk of MI of 0.21, compared with 1.14 in the men in the placebo group who took NSAIDs for 1-59 days a year.

When the researchers used a shorter cutoff point for NSAID use of never, 1-29 days per year, and 30 or more days per year, different but nonsignificant risks associated with NSAID use appeared in subjects in the aspirin group who took NSAIDs for at least 30 days per year, compared with those who never took NSAIDs.

The mostly homogenous population (92% white men) limited the study, but the researchers said that they had no reason to believe that the study subjects differed from the general population as far as how aspirin and NSAIDs interact in the body. In addition, the researchers didn't know the brands or dosages of NSAIDs taken by study subjects, and the effects are averages based on overall NSAID use.

The study was the first to examine the possible effect of NSAIDs on the cardio-protective effects of low-dose aspirin in the setting of a randomized clinical trial, so the results are probably valid, said Dr. Marc C. Hochberg, a rheumatology specialist and professor of medicine at the University of Maryland.

The data suggest that "people who use low-dose aspirin for heart protection should take COX-2 selective inhibitors rather than nonselective NSAIDs for treatment of arthritis and musculoskeletal pain," Dr. Hochberg said in an interview. Arthritis patients at high risk for upper gastrointestinal problems because of their NSAID use should add a proton pump inhibitor to their therapy.

But patients shouldn't rush to discontinue NSAID use without first consulting their doctors, he added. Physicians should discuss alternatives, such as acetaminophen, topical agents, or nutritional supplements, with patients to help them manage joint and other pain without sacrificing the benefits of aspirin.
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Author:Splete, Heidi
Publication:Internal Medicine News
Date:Oct 1, 2003
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