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Nonselective NSAIDs: Adverse cardiovascular effects

Daniel H Solomon, MD, MPH
Section Editors
Daniel E Furst, MD
Christopher P Cannon, MD
Deputy Editors
Paul L Romain, MD
Gordon M Saperia, MD, FACC


The use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a range of potential adverse effects, including an increased risk of adverse cardiovascular effects. The risk of different events varies depending upon the clinical context, medication, and dose. Both nonselective NSAIDs and cyclooxygenase (COX)-2 selective NSAIDs (coxibs) increase such risk.

When thinking about cardiovascular risk for patients treated with NSAIDs, it is important to consider the duration and frequency of therapy. Unlike the gastrointestinal side effects, which can occur soon after initiation of therapy (see "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity", section on 'Nonselective NSAIDs'), the risk of adverse cardiovascular events such as myocardial infarction, stroke, or cardiovascular death is extremely small over a short course of therapy, as might be used for patients with an acute but limited musculoskeletal injury. It should be kept in mind that in clinical practice most patients do not use their NSAIDs as regularly as in randomized trials; thus, the rates and relative risk of adverse cardiovascular events in observational studies, reflecting typical clinical care, are frequently lower than in clinical trials.

The adverse cardiovascular effects of nonselective NSAIDs and the impact on clinical decision making will be reviewed here. The cardiovascular effects of coxibs and overviews of the adverse effects of NSAID therapy are presented separately. (See "COX-2 selective inhibitors: Adverse cardiovascular effects" and "Nonselective NSAIDs: Overview of adverse effects" and "Overview of selective COX-2 inhibitors", section on 'Toxicities and possible toxicities'.)

For the purposes of this topic, nonselective NSAIDS include ibuprofen, naproxen, ketoprofen, flurbiprofen, oxaprozin, diclofenac, etodolac, tolmetin, sulindac, indomethacin, ketorolac, meloxicam, piroxicam, meclofenamate, mefenamic acid, and nabumetone (table 1). However, there are relatively sparse data regarding the cardiovascular safety of many of these agents, regarding which there is greater uncertainty than those discussed in detail in this topic. The adverse effects of aspirin are discussed separately. (See "Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases".)


For most patients in whom a nonselective nonsteroidal antiinflammatory drug (NSAID) is chosen for short-term (no more than a month) or intermittent use, we prescribe naproxen, rather than other NSAIDs. Other nonselective NSAIDs (eg, ibuprofen) are reasonable alternatives, given the low baseline risk in such patients and lack of evidence regarding the cardiovascular risks of occasional low-dose use. Nonselective NSAIDs should be used at the lowest effective dose and for the shortest duration required in order to limit adverse events. We also prefer naproxen to other NSAIDs for patients who require long-term (over a month) use.


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Literature review current through: Sep 2016. | This topic last updated: Sep 8, 2016.
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