Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial

Abstract

Background Several studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events. Aims We aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI). Methods This is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23‐month ticagrelor monotherapy following 1‐month dual antiplatelet therapy [DAPT]) with the reference arm (12‐month aspirin monotherapy following 12‐month DAPT) after PCI. Patient‐oriented composite endpoints (POCEs: all‐cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time‐dependent covariate in patients with the experiment or reference antiplatelet arm. Results Among 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12–1.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92–1.19; pinteraction = 0.035). During the second‐year follow‐up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27–1.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83–1.28; pinteraction = 0.008). Conclusions In contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies. Clinical Trial Registration URL: https://clinicaltrials.gov

The Efficacy and Safety of Proton Pump Inhibitors Combining Dual Antiplatelet Therapy in Patients with Coronary Intervention: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

“…The GLOBAL LEADERS trial also demonstrated that the combination of PPI and ticagrelor monotherapy might be safe. Nevertheless, the utilization of PPIs was not randomized, and the unknown confounding factors should be considered [ 36 ]. In our study, only one included RCT with 86 patients compared the combination of PPI with aspirin and ticagrelor.…”

Emerging Clinical Problem of Resistance to Antiplatelet Therapy in Primary Prevention and Treatment of Cardiovascular Events in People Living with HIV: Conundrum despite Effective cART

“…Similarly, omeprazole decreases antiplatelet effects of clopidogrel as evaluated by VASP PRI [100]. Clinically, patients on aspirin or clopidogrel plus PPI have increased incidence of major adverse cardiovascular events [101,102]. By acting on platelet cyclooxygenase, over-the-counter treatment (OTC) NSAIDs displace aspirin from its active site, thus decreasing its effectiveness [103].…”

Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

“…No significant differences were found in infarction related artery perfusion indexes, incidence of stent thrombosis, platelet indicators, platelet activation and aggregation, myocardial necrosis biomarkers and brain natriuretic peptide levels, and incidence of ischemic endpoint events and other tissue and organ bleeding events[ 103 ]. A sub-analysis of the randomized GLOBAL LEADERS trial[ 104 ] compared the experimental antiplatelet arm (23-mo ticagrelor monotherapy following 1-mo DAPT) with the reference arm (12-mo aspirin monotherapy following 12-mo DAPT) after PCI. In the reference group, the use of PPIs was independently associated with Patient Oriented Composite Endpoints (POCEs: All-cause mortality, MI, stroke, or repeat revascularization; HR: 1.27) and its individual components, whereas it was not in the experimental arm.…”

“…In the reference group, the use of PPIs was independently associated with Patient Oriented Composite Endpoints (POCEs: All-cause mortality, MI, stroke, or repeat revascularization; HR: 1.27) and its individual components, whereas it was not in the experimental arm. Thus, in contrast to conventional antiplatelet strategy, there is no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events[ 104 ].…”