Avoid NSAIDs after Myocardial Infarction

Source: Schjerning-Olsen AM, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: A nationwide cohort study. Circulation 2011;123:2226-2235.

Current American College of Cardiology/ American Heart Association (ACC/AHA) Guidelines recommend withholding non-steroidal anti-inflammatory drugs (NSAIDs) from patients who have suffered a myocardial infarction (MI) and substitution of another analgesic such as acetaminophen. If NSAID therapy is unavoidable, the guidelines recommend the shortest duration possible. However, there are few data about the cardiovascular risk of each individual NSAID agent, and what constitutes a safe duration of therapy. Schjerning-Olsen and colleagues studied the effects of NSAID use, and the duration of use, in adults after their first MI. They made use of the nationwide registries of hospitalization and drug dispensing in Denmark to identify individuals with their first MI, and then identified those who had purchased NSAIDS. Linking the patient hospitalization registry and the death registry identified those who were readmitted with recurrent MI and those who died. They identified 102,138 patients with first-time MI over a 10-year period; 82% (83,675) were discharged alive and were included in the analysis. Of these, at least one prescription for NSAIDs was filled for 35,405 patients (42%).

The use of NSAIDs following MI was associated with an approximately 50% increased risk of death, as well as an increase in the combined endpoint of death or MI. This risk increased within the first week and persisted throughout the entire duration of NSAID use. The authors then analyzed the five most popularly prescribed individual NSAIDS in Denmark: celecoxib, rofecoxib, diclofenac, ibuprofen, naproxen; the researchers combined all the other less commonly used agents into a single group. Similar increases in the rate of death were seen with all five individual NSAIDs and with the combined group, suggesting there is no "safe" NSAID in patients after MI. In addition, the COX-2 selective agents celecoxib and rofecoxib did not appear to have lower or higher risk of death or recurrent MI.

The only real difference between agents was that diclofenac appeared to have the highest rate of death and recurrent MI, and this risk was elevated early. Rofecoxib, celecoxib, ibuprofen, naproxen, and the combined group did not have an increased risk within the first 7 days of use, but the risk did rise after that to a similar order of magnitude. If anything, naproxen appeared to have the lowest rate of death or MI. Importantly, the risk returned to baseline shortly after ceasing NSAID use, except in the rofecoxib group.

The authors conclude that even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.

This is a very large study utilizing nationwide registries, and thus has a wide cross-section of patients. In addition, the data are strengthened by the fact that the use of medications and the adjudication of repeat hospitalization and death are very complete in these datasets. It is important to acknowledge, however, that the datasets lack complete information about comorbid conditions, such as smoking status, blood pressure, left ventricular function, and renal function, that could impact the risk of recurrent MI and death. Thus, it is possible that unmeasured confounders such as these that would alter the risk of death or MI could be present. Furthermore, the population in Denmark is more racially homogeneous than in the United States, so differences in the effects of NSAIDs in different ethnic groups are not addressed here. Thus, these data should not be considered definitive proof of toxicity of NSAIDs, but rather they should be considered hypothesis-generating.

Other clinical studies and registries have suggested that NSAIDs in patients with coronary artery disease may increase the risk of MI or death. The current study supports previous trials and extends the findings by suggesting that not even short duration of NSAID treatment is safe. It is unlikely that we will ever have a randomized controlled trial of NSAID use after MI, so as clinicians we will be left to use the available data from these types of observational studies. This study supports the current guidelines that recommend patients try to avoid NSAID use after MI.