Risks of colorectal neoplasms and cardiovascular thromboembolic events after the combined use of selective COX-2 inhibitors and aspirin with 5-year follow-up: a meta-analysis.

Abstract

We aimed to evaluate the association between selective COX-2 inhibitors (coxibs) and the risk of colorectal neoplasms and vascular events with and without low-dose aspirin. We searched for randomized controlled trials and comparative studies in PubMed, EMBASE and Cochrane Library databases using pertinent key terms. Risk ratios (RRs) were calculated for each study with a fixed- or random-effects model. Eight clinical studies with 44 566 subjects were eligible. The use of coxib significantly reduced the overall risk of colorectal neoplasms by 21% (RR = 0.79, 95% CI 0.70-0.89; P = 0.000). The chemopreventive effect of coxibs was beneficial in the first year (RR = 0.74, 95% CI 0.58-0.94; P = 0.013), marginal in the third year (RR = 0.79, 95% CI 0.63-1.01; P = 0.059) and counterproductive in the fifth year (RR = 1.65, 95% CI 1.23-2.21; P = 0.001). Compared with the use of aspirin alone, combined use of coxib and aspirin for 3 years increased the risk of a colorectal neoplasm by 80% in the fifth year (RR = 1.80, 95% CI 1.22-2.66; P = 0.003) but decreased by 79% and 30%, respectively, the risks of cardiovascular thromboembolic events (RR = 1.79, 95% CI 1.33-2.41; P = 0.0001) and renal impairment/hypertension (RR = 1.30, 95% CI 1.09-1.54; P = 0.003) caused by coxib use alone. Coxibs may reduce the overall risk of colorectal neoplasms, but the chemopreventive effects are attenuated over time. When participants take low-dose aspirin simultaneously, coxibs may not be useful for chemoprevention of colorectal neoplasm.