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Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study.

Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.39). 12/2008; 85(2):190-7.
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ABSTRACT Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death and myocardial infarction associated with the use of NSAIDs. Participants in the study were selected from the Danish population and were defined as healthy according to a history of no hospital admissions and no concomitant selected pharmacotherapy. The source population consisted of 4,614,807 individuals, of whom 1,028,437 were included in the study after applying selection criteria. Compared to no NSAID use, hazard ratios (95% confidence limits) for death/myocardial infarction were 1.01 (0.96-1.07) for ibuprofen, 1.63 (1.52-1.76) for diclofenac, 0.97 (0.83-1.12) for naproxen, 2.13 (1.89-2.41) for rofecoxib, and 2.01 (1.78-2.27) for celecoxib. A dose-dependent increase in cardiovascular risk was seen for selective COX-2 inhibitors and diclofenac. Caution should be exercised in NSAID use in all individuals, and particularly high doses should be avoided if possible.

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    • "These include numerous harmful effects such as mucosal lesions, bleeding, peptic ulcers, and intestinal perforation [1] [2]. Other studies, meanwhile, have suggested that the side effects of NSAIDs are not limited only to GIT but extend to other serious complications such as acute renal failure, nephrotic syndrome, hypertension, and cardiovascular toxicity [3] [4] [5]. Recently, therefore, much effort has been devoted towards the discovery of alternative anti-inflammatory compounds of plant origin as potential natural and safe medicines without the harmful side effects of NSAIDs [6] [7] [8] [9] [10] [11]. "
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    • "However, selective COX-2 inhibitors are associated with an increased risk of cardiovascular events (eg, myocardial infarction and stroke), and 2 widely used COX-2 inhibitors, rofecoxib and valdecoxib, were withdrawn from the market due to concerns about their cardiovascular safety (Altman, 2009; Andersohn et al., 2006; Caldwell et al., 2006). The cardiovascular risks associated with selective COX-2 inhibitors have been confirmed by the results of several studies (Bombardier et al., 2000; Bresalier et al., 2005; Graham et al., 2005; Nussmeier et al., 2005; Solomon et al., 2005), and in recent years these findings have been extended to nonselective NSAIDs, particularly diclofenac (Fosbol et al., 2009; Gislason et al., 2009; Hammad et al., 2008; McGettigan & Henry, 2006; Schjerning Olsen et al., 2011). In patients with a history of myocardial infarction, Schjerning Olsen and colleagues observed that NSAID treatment durations ranging from less than 7 days to more than 90 days were associated with significantly increased risks of death and recurrent myocardial infarction. "
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    • "Gastrointestinal and kidney toxicity have been related to non-selective inhibition of cyclooxygenases, and have decreased after development of selective COX-2 inhibitors (Lafrance and Miller, 2009; Mitchell and Warner, 1999). However, the occurrence of heart and liver failure remains (Fosbol et al., 2009; Laine et al., 2009), indicating that additional mechanisms of toxicity exist. "
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