Aspirin and the Harmful Effect of NSAIDs

Abstract

The article by Bavry et al1Bavry A.A. Khaliq A. Gong Y. Handberg E.M. Cooper-DeHoff R.M. Pepine C.J. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease.Am J Med. 2011; 124: 614-620Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar reporting the recurrence of myocardial infarction after the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with established cardiovascular disease is of great interest and of relevance for clinicians working in the “real world.” Although the mechanism for the harmful effect of NSAIDs remains poorly understood, it is feasible that NSAIDs would induce an imbalance between cyclooxygenase-2 (COX-2)-derived prostacyclin (PGI2) and the COX-1-derived thromboxane (TXA2). COX-2 inhibitors do not affect TXA2 level, may increase platelets reactivity, and could exert prothrombotic effects. Aspirin decreases both COX-1-derived TXA2 and PGI2, preventing the imbalance of these 2 prostanoids. In the Bavry et al study, it is possible to suppose that some patients were prescribed NSAIDs because of rheumatoid arthritis. Differences in cardiovascular outcomes between chronic and nonchronic NSAIDs groups are very significant (for death, myocardial infarction, stroke, P=.0003; cardiovascular mortality, P <.0001; fatal and nonfatal myocardial infarction, P=.0017), but these differences as well as the corresponding numbers needed to harm (144, 100, and 250, respectively) might be affected by confounding factors such as rheumatoid arthritis and other inflammatory diseases associated with cardiovascular events. The beneficial effect of aspirin in the secondary prevention of coronary artery diseases is well known. We reported a reduction of events in patients with acute coronary syndromes without ST elevation treated with aspirin and the preferential COX2 inhibitor meloxicam (P between .025 and .004; number needed to treat between 3.5 and 5.5).2Altman R. Luciardi H.L. Muntaner J. et al.Efficacy assessment of meloxicam, a preferential cyclooxygenase-2 inhibitor, in acute coronary syndromes without ST-segment elevation: the Nonsteroidal Anti-Inflammatory Drugs in Unstable Angina Treatment-2 (NUT-2) pilot study.Circulation. 2002; 106: 191-195Crossref PubMed Scopus (100) Google Scholar A large inception cohort study showed that concomitant use of aspirin reduced risk of cardiovascular events when given with rofecoxib, celecoxib, sulindac, meloxicam, and indomethacin, but not when given with ibuprofen.3Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin?.Lancet. 2007; 370: 2138-2151Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar Thus, the concomitant use of aspirin may be of relevance for lowering coronary risk in patients under NSAIDs treatment. In the Bavry et al study,1Bavry A.A. Khaliq A. Gong Y. Handberg E.M. Cooper-DeHoff R.M. Pepine C.J. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease.Am J Med. 2011; 124: 614-620Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar 46.9% of the patients in the group of chronic NSAIDs users and 57.1% in nonchronic NSAIDs users also received aspirin. Even when, in this post hoc analysis, part of the information is not available (because of natural limitations of this kind of design), and even when the percentage of visits with aspirin use was detected as an independent predictor of the primary outcome, some information on this topic may be very helpful. It would be of great interest to consider the data of groups with and without aspirin presented in a separate manner to know whether patients with aspirin and any NSAIDs were protected from myocardial infarction. Harmful Effects of NSAIDs among Patients with Hypertension and Coronary Artery DiseaseThe American Journal of MedicineVol. 124Issue 7PreviewThere is limited information about the safety of chronic nonsteroidal anti-inflammatory drugs (NSAIDs) in hypertensive patients with coronary artery disease. Full-Text PDF The ReplyThe American Journal of MedicineVol. 125Issue 2PreviewI would like to thank Altman and Gonzalez for their interest in our paper, which documented a harmful association between chronic self-reported use of nonsteroidal anti-inflammatory drugs (NSAIDs) and adverse cardiovascular outcomes.1 This was due to a 2.3-fold increase in cardiovascular mortality among chronic NSAID users. Acknowledged limitations of the study were that we did not have information on the type of NSAID or indication for their use. We agree that inflammatory conditions like rheumatoid arthritis might confound this association; however, other investigations have controlled for such diseases and still documented harmful effects of NSAIDs. Full-Text PDF