Elsevier

American Heart Journal

Volume 174, April 2016, Pages 95-102
American Heart Journal

Clinical Investigation
Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial

https://doi.org/10.1016/j.ahj.2016.01.015Get rights and content

Background

Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin.

Methods and results

In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration.

Conclusions

The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.

Section snippets

Methods

The design and main findings of the PRODIGY have been previously reported.1, 24 Briefly, all-comer PCI patients receiving a balanced mixture of stents with varying anti-intimal hyperplasia potency and belonging to both first- and second-generation drug-eluting stent (DES) at 3 Italian sites were randomly allocated at 30 days to either 6 or 24 months of DAPT. Selection criteria were broad, reflecting routine clinical practice. Randomization to 6- or 24-month DAPT was stratified by center,

Results

Among 1,970 patients randomized to 6- versus 24-month DAPT at 30 days from the PCI, 738 patients (37.5%) were receiving a PPI. Most of them were treated with lansoprazole (671 patients, 90.9%), whereas the others received pantoprazole (56 patients, 7.6%) and few patients received other PPI types (omeprazole, esomeprazole, and rabeprazole, 1.5%).

Baseline characteristics of population with PPI and without PPI are summarized in Table I, whereas Table II describes their characteristics in the

Discussion

The present post hoc analysis from the PRODIGY randomized trial investigated the impact of concomitant PPI use on clinical outcomes in all-comer patients undergoing PCI and receiving DAPT with clopidogrel as thienopyridine component.

Although, at univariate analysis, PPI use was associated with an increased risk of ischemic and bleeding events, after multivariate adjustment, PPI therapy was no longer related to different rates of ischemic events, bleeding, or NACE at 2 years irrespective of the

Limitations

This is a post hoc not randomized and not prespecified analysis of the PRODIGY trial, and the prescription of a PPI was left to the physician's discretion.

Rates of overall but not specifically GI bleeding were evaluated and available for this analysis, so potential benefits of PPI on reducing GI bleeding events could not be analyzed.

Although multivariate adjustment was performed, it cannot be excluded that unknown/unmeasured factors may have impacted findings.

Data on PPI dosage were not

Conclusion

Overall, PPI use was not associated with an increased risk of cardiovascular events in all-comer patients undergoing PCI and receiving DAPT. Our findings do not support the need to avoid concomitant use of PPIs and DAPT with aspirin plus clopidogrel, when clinically indicated.

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