Abstract 4429: Do COX-2 Inhibitors Raise Blood Pressure More Than Non-selective NSAIDs and Placebo?: An Updated Meta-analysis of Clinical Trials Involving >130,000 Participants
Background: Both COX-2 inhibitors (COX-2i) and non-selective (NS)-NSAIDs elevate blood pressure (BP) and this may contribute to excess cardiovascular (CV) events with these agents. A number of recent large-scale prospective randomized clinical trials (RCTs) comparing COX-2i to both NS-NSAIDs and placebo have reported (including newer agents such as lumiracoxib and etoricoxib), permitting an extensive update to earlier BP analyses of agents within this class.
Methods: Our search yielded 51 randomized controlled trials involving COX-2i published before April 2008 with a total of 130,541 participants in which BP data were available. The Der Simonian and Laird random effects method was used to produce risk ratios (RR) for the development of hypertension. Disease-specific analysis was also performed (Osteoarthritis/Rheumatoid arthritis [OA/RA], Alzheimers Disease). The magnitude of absolute BP differences was determined by the Cohen method.
Results: For COX-2i versus placebo there was a RR of 1.62 (1.46 –1.80), p<0.0001 in development of new hypertension. This was mainly driven by rofecoxib with a RR 2.63 (1.67– 4.13), p<0.0001 versus placebo and an absolute systolic BP increase of 4.36 mmHg (p<0.0001). For COX-2i versus NS-NSAIDs RR was 1.35 (1.25–1.45 p<0.0001). For OA/RA, COX-2i versus placebo RR was 1.47 (1.07–2.02 p<0.05) and for COX-2i versus NS-NSAIDs, RR was 1.53 (1.31–1.78 p<0.0001). For Alzheimers Disease, COX-2i vs placebo RR was 1.42 (0.93–2.18), p=NS and COX-2i vs NSAIDs RR was 1.09 (0.90 –1.32), p=NS.
Conclusions: Based on this updated meta-analysis, COX-2i’s as a class appear to produce greater hypertension than either NS-NSAIDs or placebo. This appears to be mainly driven by specific agents such as rofecoxib. The relationship of this increased risk of hypertension to subsequent adverse CV outcomes requires further analysis and prospective RCTs.