Current Use of Nonsteroidal Antiinflammatory Drugs and the Risk of Acute Myocardial Infarction

Lorenz M. Fischer, M.Sc.; Raymond G. Schlienger, Ph.D., M.P.H.; Christian M. Matter, M.D.; Hershel Jick, M.D.; Christoph R. Meier, Ph.D., M.Sc.

Disclosures

Pharmacotherapy. 2005;25(4):503-510. 

In This Article

Abstract and Introduction

Study Objective: To evaluate the risk of acute myocardial infarction during current exposure to nonsteroidal antiinflammatory drugs (NSAIDs).
Design: Retrospective case-control analysis.
Setting: General practice offices.
Subjects: A total of 8688 case patients, aged 89 years or younger, with a first-time acute myocardial infarction and 33,923 control subjects matched on age, sex, calendar time, and general practice attended.
Intervention: The United Kingdom General Practice Research Database was searched for potential cases of first-time acute myocardial infarction between January 1995 and April 2001. Control subjects without acute myocardial infarction were identified at random.
Measurements and Main Results: Exposure to NSAIDs was assessed, and 650 case patients and 2339 control subjects were found to be currently taking NSAIDs. After adjusting for various risk factors for acute myocardial infarction (e.g., hypertension, hyperlipidemia, diabetes mellitus, ischemic heart disease, body mass index, smoking), the relative risk (expressed as odds ratio [OR]) of acute myocardial infarction was 1.07 (95% confidence interval [CI] 0.96–1.19) for subjects with current NSAID exposure compared with those not taking NSAIDs. The adjusted OR for current diclofenac use was 1.23 (95% CI 1.00–1.51), for current ibuprofen use 1.16 (95% CI 0.92–1.46), and for current naproxen use 0.96 (95% CI 0.66–1.38) compared with those not taking NSAIDs. Current aspirin use combined with current NSAID use was associated with a statistically significant risk reduction (adjusted OR 0.74, 95% CI 0.57–0.97), compared with nonuse of NSAIDs and aspirin. Current use of aspirin together with current use of ibuprofen yielded an adjusted OR of 0.69 (95% CI 0.42–1.15).
Conclusions: Our results provide additional evidence that the risk of first-time acute myocardial infarction during current use of NSAIDs is not materially altered. We found no evidence for a reduced cardioprotective effect of aspirin with concomitant NSAID use.

Results of recent studies highlight the association between intravascular inflammation and atherosclerosis and acute coronary events.[1–4] Nonsteroidal antiinflammatory drugs (NSAIDs) are used widely for the treatment of pain and inflammation. Older NSAIDs nonselectively inhibit cyclooxygenase (COX)-1 and COX-2. In general, the COX enzyme system plays an important role in the regulation of pain and inflammation at a molecular level.[5] Inhibition of COX-2 is followed by decreased prostaglandin E2 production, which is associated with antiinflammatory as well as analgesic and antipyretic effects. In addition, COX-1 inhibition decreases thromboxane A2 production, thereby reducing platelet aggregation.6 These well-documented effects may lead to a reduced risk of acute myocardial infarction during exposure to nonaspirin NSAIDs.

Several recent studies explored the risk of acute myocardial infarction in association with nonaspirin NSAIDs.[7–16] The reported risk estimates of developing myocardial infarction for those currently taking nonaspirin NSAIDs were consistently around 1.0, which means that the risk is neither substantially decreased nor increased. Most authors concluded that current use of nonaspirin NSAIDs does not substantially affect the risk of acute myocardial infarction.[7–10] Evidence from several observational studies suggests that naproxen therapy may be associated with a reduced risk of acute myocardial infarction, but these results have been inconclusive.[8,9,11,12,15,16] Furthermore, simultaneous exposure to both NSAIDs and aspirin may reduce the cardioprotective effects of aspirin.[17–19]

In a previous study, we explored the effect of discontinuation of NSAID therapy.[20] We found a statistically significant increased risk of acute myocardial infarction for subjects who stopped taking NSAIDs in the month immediately preceding the acute myocardial infarction. The risk was highest for subjects who stopped taking NSAIDs after previous long-term use.

In this study, we aimed to further explore in detail a possible effect of current NSAID expo-sure on the risk of first-time acute myocardial infarction. We mainly focused on elaboration of possible interindividual differences among NSAIDs, potential duration and dose effects, the role of underlying clinical risk factors for acute myocardial infarction, and the effect of possible interactions between NSAIDs and aspirin therapy on cardiovascular protection.

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