Efficacy and Tolerability of Proton Pump Inhibitors in the Long-term Aspirin Users: Meta-Analysis of Randomized Controlled Trials

Abstract

Introduction: Long term use of Aspirin in primary and secondary prevention of cardiovascular diseases may result in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long term aspirin users in the randomized controlled trials (RCTs), there are concerns about the long term use of PPI resulting in adverse events including pneumonia, fracture, diarrhea and cardiovascular diseases. We performed a meta-analysis of RCTs to better define the efficacy and tolerability of PPI in long term aspirin users. Methods: We searched MEDLINE, EMBASE, CENTRAL, CINHAL, ProQuest and relevant references for RCTs (inception through April 30, 2015) comprising of patients on long term aspirin with and without PPI. We performed the meta-analysis using random effects model. Results: 10 publications from nine studies with a total of 6382 randomized patients were included in the meta-analysis. Compared to control, PPI users had reduced risks of peptic ulcers [relative risk (RR): 0.19; 95% confidence interval (CI): 0.13-0.26; PPI users had reduced risks of peptic ulcers [relative risk (RR): 0.19; 95% confidence interval (CI): 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P < 0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22 (0.10-0.51); P= 0.0004] and erosive esophagitis [0.14 (0.07-0.28); P < 0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P= 0.01], heartburn [1.24 (1.18-1.31);P< 0.00001] and regurgitation [1.26 (1.13-1.40); P< 0.0001]. PPI did not increase the risks of all-cause mortality [1.72 (0.61-4.87); P= 0.31], cardiovascular mortality [1.80 (0.59-5.44); P= 0.30], nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P= 0.22], ischemic stroke/TIA [1.09 (0.34-3.53); P= 0.89] and other adverse events of nasopharyngitis, upper respiratory infections, diarrhea, constipation and hypertension. Conclusion: The PPI appears to be effective in preventing peptic ulcers and erosive esophagitis and resolution of dyspeptic symptoms without increasing adverse events, cardiac risks or mortality in long term aspirin users.