Abstract
Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]
Highlights
Dual antiplatelet therapy (DAPT) with an oral P2Y12 receptor inhibitors and aspirin constitute the foundation antiplatelet strategy after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) (Neumann et al, 2019)
The use of proton pump inhibitors (PPIs) can reduce the risk of peptic ulceration by lowering the acidity in the gastric and duodenal lumens, and may reduce the severity of GI bleeding by enhancing the stability of clots (Scheiman, 2013)
The study by Jensen et al (2017) was judged to have a high risk of blinding of participants and personnel because there was no blinding or placebo control, the authors suggested that these shortcomings had no significant impact on the outcomes as the patients in the control group were not informed about their randomization status or risk assessment
Summary
Dual antiplatelet therapy (DAPT) with an oral P2Y12 receptor inhibitors and aspirin constitute the foundation antiplatelet strategy after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) (Neumann et al, 2019). The main drawback of DAPT remains an increased incidence of bleeding events that can lead to discontinuation of therapy and most importantly, PPIs and DAPT increased mortality (Ducrocq et al, 2015). The use of proton pump inhibitors (PPIs) can reduce the risk of peptic ulceration by lowering the acidity in the gastric and duodenal lumens, and may reduce the severity of GI bleeding by enhancing the stability of clots (Scheiman, 2013). PPIs combined with DAPT presents a feasible and biologically plausible strategy to reduce GI bleeding, thereby reducing the risk of ischemic events. The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear
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