Response to Letters Regarding Article, “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”
Authors: Anne-Marie Schjerning Olsen, Emil L. Fosbøl, Jesper Lindhardsen, Fredrik Folke, Mette Charlot, Christian Selmer, Morten Lamberts, Jonas Bjerring Olesen, Lars Køber, Peter R. Hansen, Christian Torp-Pedersen, Gunnar H. Gislason
Journal: Circulation (2011)

We appreciate the interest in our article in Circulation 1 and welcome further discussion on this important topic.Dr Naimer, Dr Alla, and colleagues comment on the influence that stress and rheumatic diseases have on risk in patients.We agree that confounding by indication may influence observational studies such as ours, and that lack of information on nonsteroidal antiinflammatory drug (NSAID) treatment indication is a limitation of the study.However, our findings were consistent, and we found different degree of risk between the individual NSAIDs, which were probably all used for the same indications, a clear correlation between the degree of cyclooxygenase-2 inhibition (as reported in the literature) and risk, and a clear dose-dependent increase in risk associated with NSAIDs, respectively. 2Furthermore, given the additional evidence from randomized trials and other observational studies of adverse cardiovascular effects of selective cyclooxygenase-2 inhibitors and nonselective NSAIDs, we find no reason to believe that confounding by indication alone could have driven the results.Finally, our study cannot determine causality, but in an area where randomized studies are missing, we find it important to report associations that potentially have an impact on prognosis.Dr Alla and colleagues raise an important point regarding the effect of time elapsed after myocardial infarction (MI) on the risk associated with NSAIDs.In the current study, we focused on the effect of treatment duration on cardiovascular risk, but we are in the process of examining if time after MI influences the risk with NSAIDs, and, indeed, we presented our preliminary results on this topic in an abstract at the last American College of Cardiology meeting, indicating that NSAIDs are associated with permanently elevated risk in MI patients. 3Thus, this preliminary finding further amplifies the recommendation that NSAIDs should be avoided at any time in patients after MI, and that there is no safe therapeutic window for the use of NSAIDs in this population.Dr Alla and colleagues and Dr Altman and colleagues discuss whether aspirin modified the risk associated with NSAIDs in our study, as previously suggested by Altman et al. 4 We agree that this is an important issue, but because aspirin is available over the counter in Denmark and only 50% of the population received aspirin prescription at discharge, we were unable to determine whether aspirin modified the risk with NSAIDs in our study.We know from previous studies, however, that most patients receive aspirin at discharge after MI in Denmark, 5 and therefore we presume that the majority of patients in our study received aspirin at discharge despite the fact that only 50% claimed an aspirin prescription.Dr Alla and colleagues also raise a very interesting other point, ie, whether the use of NSAIDs may lead to premature discontinuing of aspirin, but, as previously noted, we were unable to determine aspirin adherence reliably in our study, and therefore the results from such analyses would only be speculative.We agree that the potential interaction between aspirin and NSAIDs in the post-MI population is an interesting problem that indeed warrants further investigation.