LONDON, UK—A systematic review of observational studies, case-control studies, cohort studies, and randomized controlled trials (RCTs) concluded that the overall risk of myocardial infarction (MI) with either traditional NSAIDs or cyclooxygenase-2-specific drugs (coxibs) is low, that the highest risk was associated with rofecoxib (OR 1.14-1.19), and that coxibs significantly reduced the risk of serious upper gastrointestinal (GI) events (OR 0.40).

"The overall risk of MI does not appear to be substantially increased with standard doses of most traditional NSAIDs and most cyclooxyenase-2-specific drugs," write David L. Scott, MD, and colleagues at Kings College in London.¹

The review, which appears in Annals of the Rheumatic Diseases, was based on published studies in nonrheumatic diseases (colonic adenoma) and in arthritis in which the reviewers found that

• 14 case-control studies (74,673 MI patients, 368,968 controls) showed no significant association of NSAIDs with MI in a random-effects model and a small risk of MI in a fixed-effects model (OR 1.32).
• 6 cohort studies (387,983 patient years, 1,120,812 control years) showed no significant risk of MI with NSAIDs, but a relative risk of 1.25 with rofecoxib
• 4 RCTs of NSAID use in colon cancer patients (N = 6000) showed an increased risk of MI (RR 2.68)
• 14 RCTs of arthritis patients (N = 45,425) showed more MIs with use of coxibs (OR 1.6)
• 14 RCTs in arthritis showed fewer serious upper GI events with coxibs (OR 0.40)

"Taken as a whole, the available evidence suggests that the risks of MI with NSAIDs other than rofecoxib are not large, especially when compared with preventable MI risk factors such as smoking," Dr. Scott says.

"The most definitive evidence that NSAIDs increase the risk of MI comes from RCTs in patients with colonic adenoma who, in comparison with patients with rheumatoid arthritis, do not have a specific preexisting cardiovascular risk."

Dr. Scott also notes that although RCTs in arthritis comparing coxibs with traditional NSAIDs show an excess of MI, "this finding is heavily influenced by a single RCT of rofecoxib: the VIGOR trial."

Risks are greatest with high doses of either traditional NSAIDs or coxibs given to elderly patients for prolonged periods. "The multiplicity of cardiovascular side effects with NSAIDs—particularly hypertension and fluid retention—mean that caution should also be exercised when considering the prescription of NSAIDs for patients with high cardiovascular risk. However, for some patients with severe arthritis there may be no realistic alternative, and they will need access to effective treatment with information about its risks and benefits."

The authors conclude, "Finally, economic and decision analyses do not favor cyclooxygenase-2-specific drugs in the majority of cases, although they recognize that some patients benefit from these drugs."

 

Table 1.  Case Control Studies: MI Risk and NSAID Exposure

Specific NSAID			Random-Effects Odds Ratio (OR)
Naproxen			1.03
Ibuprofen			1.08
Diclofenac			1.12
Celecoxib			1.01
Rofecoxib			1.19

Source: Adapted from Scott et al.¹

 

Table 2.  Cohort Studies: MI in Patients Taking NSAIDs

Specific NSAID			Relative Risk (RR)
Ibuprofen			0.90
Naproxen			0.96
Celecoxib			1.06
Rofecoxib			1.25

Source: Adapted from Scott et al.¹

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