Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study.
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  . 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   . 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      . "
ABSTRACT: For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, theMiddle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds ofmushrooms comprising a highly diversified group in terms of their chemical structure.They include polysaccharides, terpenoids, phenolic compounds, andmany other lowmolecularweightmolecules.The aims of this revieware to report the different types of bioactive metabolites and their relevant producers, as well as the differentmechanisms of action ofmushroomcompounds as potent anti-inflammatory agents.Mediators of Inflammation 11/2014; 2014(805841):15. DOI:10.1155/2014/805841 · 3.24 Impact Factor
Osteoarthritis - Diagnosis, Treatment and Surgery, 03/2012; , ISBN: 978-953-51-0168-0
- "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. "
ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain and inflammation. However, this group of drugs is associated with serious adverse drug reactions. Previously, we studied the mechanisms underlying toxicity of the NSAID diclofenac using Saccharomycescerevisiae as model system. We identified the involvement of several mitochondrial proteins, a transporter and cytochrome P450 activity in diclofenac toxicity. In this study, we investigated if these processes are also involved in the toxicity of other NSAIDs. We divided the NSAIDs into three classes based on their toxicity mechanisms. Class I consists of diclofenac, indomethacin and ketoprofen. Mitochondrial respiration and reactive oxygen species (ROS) play a major role in the toxicity of this class. Metabolism by cytochrome P450s further increases their toxicity, while ABC-transporters decrease the toxicity. Mitochondria and oxidative metabolism also contribute to toxicity of class II drugs ibuprofen and naproxen, but another cellular target dominates their toxicity. Interestingly, ibuprofen was the only NSAID that was unable to induce upregulation of the multidrug resistance response. The class III NSAIDs sulindac, ketorolac and zomepirac were relatively non-toxic in yeast. In conclusion, we demonstrate the use of yeast to investigate the mechanisms underlying the toxicity of structurally related drugs.Toxicology in Vitro 11/2011; 26(2):197-205. DOI:10.1016/j.tiv.2011.11.013 · 3.21 Impact Factor