Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population

Abstract

Background: Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients.

Methods: We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year.

Results: Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95-1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00-1.48). The corresponding RR was 1.34 (95% CI, 1.06-1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01-1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47-1.62) with naproxen to 1.38 (95% CI, 1.00-1.90) with diclofenac.

Conclusion: This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs.

Figures

Figure 1

Duration of use of NSAIDs and individual NSAIDs among current users (use within a month) and risk of MI. Overall, current use of tNSAIDs was associated with a RR of 1.07 (95% CI, 0.95–1.21). The corresponding estimates for diclofenac, ibuprofen and naproxen were 1.17 (0.98–1.40), 1.05 (0.86–1.28) and 0.89 (0.64–1.25), respectively. Duration of use was computed adding the periods of "consecutive" prescriptions, defined as an interval of less than one month between the end of supply of one prescription and the date of prescription of the subsequent one. Estimates are adjusted for sex, age, calendar year, anemia, smoking status, alcohol use, diabetes, hypertension, hyperlipidemia, BMI, RA, OA, prior cardiovascular disease, use of steroids, anticoagulants, aspirin, paracetamol, and NSAIDs. The duration response trends for NSAIDs, diclofenac, ibuprofen and naproxen were P = .04, P = .02, P = .47, P = .54 respectively.