NSAIDs Post Myocardial Infarction
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, University of California, San Francisco, Chief of Clinical Cardiology, University of California, San Francisco Medical Center, CA. Dr. Crawford reports no financial relationships relevant to this field of study. This article originally appeared in the December 2012 issue of Clinical Cardiology Alert.
Synopsis: The authors concluded that the use of nonsteroidal anti-inflammatory drugs was associated with an increased risk of coronary events for more than 5 years after the first myocardial infarction.
Source: Olsen AM, et al. Long term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: A nationwide cohort study. Circulation 2012;126:1955-1963.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) early after myocardial infarction (MI) has been shown to increase the risk of death or recurrent MI, but little is known about the long-term risks. Thus, this group from Denmark evaluated their national database and identified more than 99,000 patients who survived 30 days after discharge following their first MI. Of these patients, 44% filled at least one prescription for NSAIDs during a 5-year follow-up period between 1997 and 2009 when the study ended. All NSAIDs were only available by prescription, except ibuprofen. Ibuprofen was available from late 2001 on, but only in 200 mg doses with a maximum of 100 tablets. The primary outcomes were all-cause mortality and cardiac death or readmission for MI. The use of any NSAID was associated with an increased risk of death (hazard ratio [HR] 1.59, 95% confidence interval [CI], 1.49-1.69) after 1 year and HR 1.63 (CI, 1.52-1.74) after 5 years. Cardiac death or MI was also increased (HR 1.30, CI, 1.22-1.39) after 1 year and HR 1.41 (CI, 1.28-1.53) after 5 years. Diclofenac exhibited the highest increase in mortality (HRs 2.07-2.73 over the first 5 years). The authors concluded that the use of NSAIDs was associated with an increased risk of coronary events for more than 5 years after the first MI.
This population-wide observational study strongly suggests that all NSAIDs should be avoided after MI because there is a persistent increase in coronary events even after 5 years. Although naproxen exhibited the least increase in events, it has a higher likelihood of causing gastrointestinal (GI) bleeding than celecoxib, and bleeding in post-MI patients is not safe. Of course, this study does not establish causation, but there are potential mechanisms that would make the assumption of causation biologically plausible.
This is one of several cardiovascular studies to come from epidemiologists in Denmark who are mining their national databases. Such studies have the strength of large numbers, but suffer from a lack of comprehensive clinical factors that can produce unmeasured confounders. However, they believe this is unlikely because their sensitivity analysis suggests that if such a factor was present in the population at a frequency of 20%, it would have to raise the risk of mortality by about four-fold to influence the results. In fact, they repeated their analysis after excluding patients with rheumatoid arthritis and it did not change the results.
It is highly unlikely that there will ever be a randomized, controlled trial on this issue. So at this point, all NSAIDs should be avoided if possible post MI. If they do need to be used, naproxen may be the best choice unless the patient is at high risk of GI bleeding. Also, the adverse effects of NSAIDs have been shown to be dose related, so the lowest dose for the shortest time should be used. Since most NSAIDs in the United States are available over the counter, physicians must instruct their post-MI patients about this issue.