NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN PATIENTS WITH CORONARY ARTERY DISEASE: RELATIVE RISKS FROM THE PRECISION TRIAL



Jeffrey S. Borer, M.D., SUNY Downstate Medical Center and College of Medicine, Brooklyn and New York, NY, USA

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed frequently. By 2005 observational studies and small randomized trials suggested excess cardiovascular (CV) adversity with some NSAIDs. Rofecoxib, a COX-2 selective NSAID, reportedly caused relatively frequent CV adversity; effects of celecoxib, also COX-2 selective, were unclear. However, no study had prospectively assessed NSAID effects specifically on CV adversity. Therefore, the USFDA mandated a prospective comparison of CV (and GI and renal) adversity with celecoxib versus the non-selective ibuprofen and naproxen. The resulting Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen (PRECISION) trial included 24,081 arthritis patients with known or high risk for coronary artery disease (CAD), given either celecoxib (200-400mg daily), ibuprofen 1800-2400mg daily) or naproxen (750-1000mg daily). Approximately half received low dose aspirin; most received antacid drugs. Mean exposure (months) to celecoxib was 20.8±16.0, to naproxen 20.5±15.9 and to ibuprofen 19.6±16.0. The hazard ratio (HR [95% CI]) and noninferiority P-values for the primary ITT analysis were 0.93 (0.76,1.13), P<0.001 for celecoxib versus naproxen and 0.85 (0.70,1.04), P<0.001 for celecoxib versus ibuprofen. On-treatment, HR for celecoxib versus naproxen was 0.90 (0.71,1.15), P<0.001, and versus ibuprofen was 0.81 (0.65,1.02), P<0.001. Celecoxib caused the fewest CV events, the least hypertension and the fewest serious GI and renal events among the NSAIDs. The rate of CV death was lower for celecoxib versus ibuprofen (on-treatment population), HR 0.64 (95% CI 0.42 to 0.99), P=0.04; all-cause mortality was lower for celecoxib versus naproxen in the ITT population, HR 0.80 (95% CI 0.63 to 1.00), P=0.052. In summary, in arthritic patients with or at high risk of CAD, to minimize CV, GI and renal adversity, celecoxib at anti-arthritic doses is relatively favorable compared with ibuprofen and, to a lesser extent, naproxen. COX-2 selectivity appears NOT to confer excess CV (or GI or renal) risk compared with non-selectivity.