As part of the Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project, we reviewed the incidence of cardiovascular (CV) and gastrointestinal (GI) events associated with the use of this category of drugs. We collected data from published meta-analyses (MAs) of clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs). The Medline, Cochrane, ISI, and SCOPUS databases were systematically searched for MAs of NSAID clinical trials that could potentially contain data on adverse incidents such as myocardial infarction (MI), cerebrovascular events (CeVs), stroke, thromboembolic events (ThEs), heart failure (HF), gastrointestinal bleeding (GIB), and perforation, ulcer, and bleeding (PUB). From 1,733 identified references, 29 MAs were selected for the review. This allowed 109 estimations of incidence rates of CV adverse events and 26 estimations of incidence rates for GI adverse events. No data were found on hemorrhagic stroke or LGIB. Coxibs were studied in more MAs than traditional NSAIDs were (21 MAs for coxibs vs. 7 for traditional NSAIDs; one meta-analysis studied both). Many NSAIDs were not considered in any of the MAs. Our systematic review of MAs included information on the incidence of CV and GI events and identified important knowledge gaps regarding, in particular, the CV safety of traditional NSAIDs.
OBJECTIVES: To update a previous report on the comparative benefits and harms of oral non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, over-the-counter supplements (chondroitin and glucosamine), and topical agents (NSAIDs and rubefacients, including capsaicin) for osteoarthritis.
DATA SOURCES: Ovid MEDLINE (1996–January 2011), the Cochrane Database (through fourth quarter 2010), and reference lists.
REVIEW METHODS: We included randomized trials, cohort studies, case-control studies, and systematic reviews that met predefined inclusion criteria. For each study, investigators abstracted details about the study population, study design, data analysis, followup, and results, and they assessed quality using predefined criteria. We assessed the overall strength of each body of evidence using predefined criteria, which included the type and number of studies; risk of bias; consistency; and precision of estimates. Meta-analyses were not performed, though pooled estimates from previously published studies were reported.
RESULTS: A total of 273 studies were included. Overall, we found no clear differences in efficacy for pain relief associated with different NSAIDs. Celecoxib was associated with a lower risk of ulcer complications (RR 0.23, 95% CI 0.07 to 0.76) compared to nonselective NSAIDs. Coprescribing of proton pump inhibitors, misoprostol, and H2-antagonists reduce the risk of endoscopically detected gastroduodenal ulcers compared to placebo in persons prescribed NSAIDs. Celecoxib and most nonselective, nonaspirin NSAIDs appeared to be associated with an increased risk of serious cardiovascular (CV) harms. There was no clear association between longer duration of NSAID use or higher doses and increased risk of serious CV harms. There were no clear differences between glucosamine or chondroitin and oral NSAIDs for pain or function, though evidence from a systematic review of higher-quality trials suggests that glucosamine had some very small benefits over placebo for pain. Head-to-head trials showed no difference between topical and oral NSAIDs for efficacy in patients with localized osteoarthritis, lower risk of gastrointestinal (GI) adverse events, and higher risk of dermatological adverse events, but serious GI and CV harms were not evaluated. No head-to-head trials compared topical salicylates or capsaicin to oral NSAIDs.
CONCLUSIONS: Each of the analgesics evaluated in this report was associated with a unique set of risks and benefits. Choosing the optimal analgesic for an individual with osteoarthritis requires careful consideration and thorough discussion of the relevant tradeoffs.
As part of the Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project, we reviewed the incidence of cardiovascular (CV) and gastrointestinal (GI) events associated with the use of this category of drugs. We collected data from published meta-analyses (MAs) of clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs). The Medline, Cochrane, ISI, and SCOPUS databases were systematically searched for MAs of NSAID clinical trials that could potentially contain data on adverse incidents such as myocardial infarction (MI), cerebrovascular events (CeVs), stroke, thromboembolic events (ThEs), heart failure (HF), gastrointestinal bleeding (GIB), and perforation, ulcer, and bleeding (PUB). From 1,733 identified references, 29 MAs were selected for the review. This allowed 109 estimations of incidence rates of CV adverse events and 26 estimations of incidence rates for GI adverse events. No data were found on hemorrhagic stroke or LGIB. Coxibs were studied in more MAs than traditional NSAIDs were (21 MAs for coxibs vs. 7 for traditional NSAIDs; one meta-analysis studied both). Many NSAIDs were not considered in any of the MAs. Our systematic review of MAs included information on the incidence of CV and GI events and identified important knowledge gaps regarding, in particular, the CV safety of traditional NSAIDs.
