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Review
. 2019 Apr;36(Suppl 1):15-24.
doi: 10.1007/s40266-019-00660-1.

Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say?

Cyrus Cooper  1   2   3 , Roland Chapurlat  4 , Nasser Al-Daghri  5 , Gabriel Herrero-Beaumont  6 , Olivier Bruyère  7   8 , François Rannou  9 , Roland Roth  10 , Daniel Uebelhart  11 , Jean-Yves Reginster  7   5   8
Affiliations
Review

Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say?

Cyrus Cooper et al. Drugs Aging. 2019 Apr.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.

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Conflict of interest statement

Olivier Bruyère reports grants from Biophytis, IBSA, MEDA, Servier, SMB, and Theramex, outside of the submitted work. Cyrus Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB, outside of the submitted work. Jean-Yves Reginster reports grants from IBSA-Genevrier, Mylan, CNIEL, and Radius Health (through institution), consulting fees from IBSA-Genevrier, Mylan, CNIEL, Radius Health, and Pierre Fabre, fees for participation in review activities from IBSA-Genevrier, MYLAN, CNIEL, Radius Health, and Teva, payment for lectures from AgNovos, CERIN, CNIEL, Dairy Research Council, Echolight, IBSA-Genevrier, Mylan, Pfizer Consumer Health, Teva, and Theramex, outside of the submitted work. François Rannou reports grants from APHP, INSERM, University Paris Descartes, and Arthritis (Road Network), and consulting fees from Pierre Fabre, Expanscience, Thuasne, Servier, Genevrier, Sanofi Aventis, and Genzyme, outside of the submitted work. Roland Chapurlat, Nasser Al-Daghri, Gabriel Herrero-Beaumont, Roland Roth, and Daniel Uebelhart have not conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Actions of cyclo-oxygenase (COX) enzymes and mechanisms underlying drug-induced side effects of non-steroidal anti-inflammatory drugs (NSAIDs). GFR glomerular filtration rate, GI gastrointestinal, PGE2 prostaglandin E2, PGI2 prostacyclin, TXA2 thromboxane
Fig. 2
Fig. 2
Risk of upper gastrointestinal adverse events with cyclo-oxygenase-2 inhibitors (Coxibs) vs. non-steroidal anti-inflammatory drugs (NSAIDs) plus proton pump inhibitor (PPI). CI confidence interval, M-H Mantel-Haenszel. Reproduced from Wang et al. [33]; copyright permission granted by Wolters Kluwer Health Inc, 2018
Fig. 3
Fig. 3
Risk of cardiovascular outcomes with all non-steroidal anti-inflammatory drugs (NSAIDs). CV cardiovascular, MI myocardial infarction. Each NSAID was compared against all other NSAIDs in the study for each outcome. NSAIDs denoted by (*) represent statistically significant findings. Reproduced from Gunter et al. [35]; Copyright permission granted by John Wiley & Sons Inc, 2018
See this image and copyright information in PMC

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