Painful musculoskeletal conditions commonly coexist with cardiovascular disease. Older persons with elevated body mass index are at risk of degenerative arthritis, and low back pain as well as cardiovascular disease. Inflammatory arthritis, including rheumatoid arthritis, lupus, and psoriatic arthritis, are associated with an elevated risk of cardiovascular events. The overlapping epidemiology of arthritis and cardiovascular disease ensures that analgesics will always be widely prescribed to patients at risk for future cardiac events. Thus, even though the selective and some nonselective nonsteroidal antiinflammatory drugs (NSAIDs) are known to be associated with cardiac events, they are widely used even in patients with known cardiovascular disease.
Article see p 155
Several randomized controlled trials comparing COX-2 selective NSAIDs (eg, celecoxib, rofecoxib, and valdeoxib) with nonselective agents or placebo found an elevated risk of cardiac events with the selective agents.1–3 The cardiac risk observed with the COX-2 selective agents appears to differ by agent and by dosage. However, a number of nonselective NSAIDs also may be associated with cardiovascular risk, such as diclofenac.4 Information about nonselective NSAID risk has primarily been derived from observational data, as few randomized controlled trials of adequate duration have examined cardiovascular risk with these agents. What can be learned from observational data regarding the cardiovascular risk of NSAIDs?
Although randomized controlled trials serve as the standard for judging a drug’s efficacy, there are many reasons why trials may not be as useful for assessing toxicity. First, efficacy for arthritis is typically judged at 12 weeks of follow-up and does not require more than several hundred subjects, resulting in too little person-time to accrue adequate numbers of cardiac events. The cardiovascular risk of selective COX-2 NSAIDs was best observed in the longer-term gastrointestinal safety studies that enrolled thousands …
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