Nonselective NSAIDs: Adverse cardiovascular effects
- Daniel H Solomon, MD, MPH
Daniel H Solomon, MD, MPH
- Matthew H. Liang Distinguished Chair in Arthritis and Population Health
- Professor of Medicine
- Harvard Medical School
- Section Editors
- Daniel E Furst, MD
Daniel E Furst, MD
- Section Editor — Treatment Issues in Rheumatology
- Professor of Rheumatology, University of Washington, Seattle
- Professor of Rheumatology, Washington University of Florence, Florence, Italy
- Professor of Rheumatology, University of California in Los Angeles (Emeritus)
- Director of Research, Pacific
- Christopher P Cannon, MD
Christopher P Cannon, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Harvard Medical School
- Deputy Editors
- Paul L Romain, MD
Paul L Romain, MD
- Deputy Editor — Rheumatology
- Assistant Professor of Medicine, Part-time
- Harvard Medical School
- Gordon M Saperia, MD, FACC
Gordon M Saperia, MD, FACC
- Senior Deputy Editor — UpToDate
- Deputy Editor — Cardiovascular Medicine
- Assistant Professor of Medicine
- Tufts University School of Medicine
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). There appears to be heterogeneous cardiovascular risk across NSAIDs, although precise risk data for many of these agents are limited. The adverse effects of aspirin are discussed separately. (See "Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases".)
PATIENTS WITHOUT KNOWN CARDIOVASCULAR DISEASE
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 nonselective NSAIDs for patients who require long-term (over a month) use.
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- PATIENTS WITHOUT KNOWN CARDIOVASCULAR DISEASE
- Risk of myocardial infarction, stroke, and death
- - Safety compared with placebo
- - Safety comparison between nonselective NSAIDs
- Risk of developing heart failure
- Risk of blood pressure elevation
- Risk of atrial fibrillation
- Risk of venous thromboembolism
- Comparison with alternative agents
- PATIENTS WITH CARDIOVASCULAR DISEASE
- Patients with known coronary heart disease
- Patients with heart failure
- Patients with hypertension
- PATIENTS WITH SYSTEMIC INFLAMMATORY DISORDERS
- PATIENTS TAKING ASPIRIN FOR PREVENTION
- RECOMMENDATIONS OF OTHERS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS