Evidence-based Medicine Study Of Acid-suppressive Agents In The Prevention Of Anti-platelet Drugs Associated Upper Gastrointestinal Injuries

SECTION ONEAIM:To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA) associated gastrointestinal (GI) ulcer and bleeding.METHODS:We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to December 2013, and checked conference abstracts of randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI events in patients taking LDA. The preventive effects of PPIs were compared with the control group (taking placebo, cytoprotective agent and H2RA) in LDA associated upper GI injuries. Meta-analysis was performed using RevMan 5.1 software.RESULTS:We evaluated 8780 participants in ten RCTs. The result of meta-analysis showed that PPIs decreased the risk of LDA associated upper GI ulcers (OR=0.16, 95% CI:0.12-0.23) and bleeding (OR=0.27,95% CI:0.16-0.43) compared with control group. For the patients treated with dual anti-platelet therapy of LDA and clopidogrel, PPIs were able to prevent the LDA associated GI bleeding (OR=0.36, 95%CI:0.15-0.87) without increasing the major adverse cardiovascular events (MACE) (OR=1.00,95% CI:0.76-1.31). CONCLUSIONS:PPIs are effective in preventing LDA associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and clopidogrel did not increase the MACE.SECTION TWOAIM:This study compared PPIs and histamine H2 receptor antagonists (H2RAs) for prevention of LDA-related GI erosion, ulcer and bleeding. METHODS:Electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Data were searched from the date of their establishment to December 31,2013. RESULTS:RCTs comparing PPIs and H2RAs for prevention of GI injury associated with LDA were collected. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta-analysis showed that PPIs were superior to H2RAS for prevention of LDA-associated GI erosion/ulcer (OR=0.28,95% CI:0.16-0.50) and bleeding (OR=0.28,95%CI:0.14,0.59)CONCLUSIONS:PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs.SECTION THREEAIM:To determine whether famotidine is noninferior to rabeprazole in the prevention of dual-antiplatelet therapy associated upper gastrointestinal bleeding for coronary heart disease patients without helicobacter pylori infection. METHODS:A multi-center, randomized, Non-Inferiority Trial was performed in 170 coronary heart disease patients who need dual antiplatelet therapy without helicobacter pylori infection. Patients received either rabeprazole or famotidine orally for one year. The primary end point was upper gastrointestinal bleeding. RESLUTS:3 patients in famotidine group and 1 in rabeprazole group reached the primary end point. With PP analysis, the efficiency rate for prevention of dual antiplatelet drugs associated GI bleeding in the famotidine group compared with the rabeprazole group was 2.5% (95% CI,-0.022-0.072), which did not cross the specified noninferiority boundary of 10%. CONCLUSIONS:Famotidine was noninferior to rabeprazole in the prevention of dual-antiplatelet therapy associated upper gastrointestinal bleeding for coronary heart disease patients without helicobacter pylori infection.