Meta-analysis of efficacy and safety of proton pump inhibitors with dual antiplatelet therapy for coronary artery disease.

Abstract

BACKGROUND\nThere is inconsistency in the literature regarding the clinical effects of proton pump inhibitors (PPI) when added to dual antiplatelet therapy (DAPT) in subjects with coronary artery disease (CAD). We performed meta-analysis stratified by study design to explore these differences.\n\n\nMETHODS AND RESULTS\n39 studies [4 randomized controlled trials (RCTs) and 35 observational studies) were selected using MEDLINE, EMBASE and CENTRAL (Inception-January 2018). In 221,204 patients (PPI\u202f=\u202f77,731 patients, no PPI =143,473 patients), RCTs restricted analysis showed that PPI did not increase the risk of all-cause mortality (Risk Ratio (RR): 1.35, 95% Confidence Interval (CI), 0.56-3.23, P\u202f=\u202f0.50, I2\u202f=\u202f0), cardiovascular mortality (RR: 0.94, 95% CI, 0.25-3.54, P\u202f=\u202f0.92, I2\u202f=\u202f56), myocardial infarction (MI) (RR: 0.97, 95% CI, 0.62-1.51, P\u202f=\u202f0.88, I2\u202f=\u202f0) or stroke (RR: 1.11, 95% CI, 0.25-5.04, P\u202f=\u202f0.89, I2\u202f=\u202f26). However, PPI significantly reduced the risk of gastrointestinal (GI) bleeding (RR: 0.32, 95% CI, 0.20-0.52, P\u202f<\u202f0.001, I2\u202f=\u202f0). Conversely, analysis of observational studies showed that PPI significantly increased the risk of all-cause mortality (RR: 1.25, 95% CI, 1.11-1.41, P\u202f<\u202f0.001, I2\u202f=\u202f82), cardiovascular mortality (RR: 1.25, 95% CI, 1.03-1.52, P\u202f=\u202f0.02, I2\u202f=\u202f71), MI (RR: 1.30, 95% CI, 1.16-1.47, P\u202f<\u202f0.001, I2\u202f=\u202f82) and stroke (RR: 1.60, 95% CI, 1.43-1.78, P\u202f<\u202f0.001, I2\u202f=\u202f0), without reducing GI bleeding (RR: 0.74, 95% CI, 0.45-1.22, P\u202f=\u202f0.24, I2\u202f=\u202f79).\n\n\nCONCLUSION\nMeta-analysis of RCTs endorsed the use of PPI with DAPT for reducing GI bleeding without worsening cardiovascular outcomes. These findings oppose the negative observational data regarding effects of PPI with DAPT.