Cardiovascular safety of proton pump inhibitors in post-percutaneous coronary intervention patients receiving dual antiplatelet therapy: A meta-analysis

Abstract

BACKGROUND

Proton pump inhibitors (PPI) are often prescribed alongside dual antiplatelet therapy (DAPT) to mitigate risk of gastrointestinal (GI) bleeding. Despite GI protection, there is emerging concerns about potential interference with antiplatelet efficacy and increased cardiovascular risk.

AIM

To determine the cardiovascular impact of PPI on DAPT efficacy.

METHODS

Online databases were searched from inception until April 2025, and a total of three randomized controlled trials (RCTs) and five observational studies were identified. Data were pooled using a random-effects model, and results were generated using Review Manager in form of risk ratios (RRs) with 95% confidence intervals (CIs).

RESULTS

The RCTs showed no association between PPI use and risk of ACS (RR = 0.84; 95%CI: 0.70-1.00; P = 0.005), cardiac death (RR = 1.25; 95%CI: 0.35-4.38; P = 0.73) and all-cause mortality (RR = 0.77; 95%CI: 0.370-1.60; P = 0.49). Similarly, observational studies confirmed no significant effect of PPI on risk of ACS (RR = 1.22; 95%CI: 0.89-1.66; P = 0.21), cardiac death (RR = 1.30; 95%CI: 0.66-2.58; P = 0.45), all-cause mortality (RR = 1.21; 95%CI: 0.96-1.53; P = 0.10), stent thrombosis (RR = 1.63; 95%CI: 0.83-3.21; P = 0.16), revascularization (RR = 1.08; 95%CI: 0.59-1.97; P = 0.81) and ischemic stroke (RR = 0.82; 95%CI: 0.34-2.02; P = 0.67), yet and increased risk of major adverse cardiovascular event (RR = 1.29; 95%CI: 1.11-1.50; P = 0.001).

CONCLUSION

Even though RCTs confirmed that PPI use is generally safe in post-percutaneous coronary intervention patients receiving DAPT, observational studies raised suspicion of increased risk warranting a need for further studies.

Keywords: Proton pump inhibitors; Dual antiplatelet therapy; Percutaneous coronary intervention; Major cardiovascular adverse events; Cardiac revascularization

Core Tip: This meta-analysis provides a robust, clinically relevant evaluation of proton pump inhibitor use in patients receiving dual antiplatelet therapy after percutaneous coronary intervention by integrating evidence from both randomized trials and real-world observational studies. Importantly, it demonstrates that concerns regarding impaired antiplatelet efficacy do not translate into increased risks of acute coronary syndrome, mortality, stent thrombosis, or stroke in randomized data, suggesting that adverse signals seen in observational studies likely reflect residual confounding rather than true harm. These findings shift the focus from theoretical drug-drug interactions to patient-centered clinical outcomes and support the safe, guideline-concordant use of PPIs for gastrointestinal protection in appropriately selected post-percutaneous coronary intervention patients.