Original Title: Proton Pump Inhibitors, Platelet Reactivity, and Cardiovascular Outcomes After Drug-Eluting Stents in Clopidogrel-Treated Patients. The ADAPT-DES Study.

Some proton pump inhibitors interfere with clopidogrel metabolism and could attenuate P2Y12 reception. Prior observational and randomized studies have reported contradicting results on the clinical significance of this drug interaction.

The aim of this trial was the extensive study of the interaction between proton pump inhibitors and clopidogrel on platelet reactivity and clinical events.

Platelet reactivity was measured using the VerifyNowassay after clopidogrel and successful implantation of DES in 11 centers in Germany and US.

Proton pump inhibitors were indicated at physicians’ criteria and patients were followed up for 2 years.
2697 (31.4%) out of8582 enrolled patients, were receiving a proton pump inhibitor at the time of PCI.

After adjusting for baseline characteristics, proton pump inhibitors were associated independently with high platelet reactivity (OR 1.38, IC 95% 1.25–1.52; p=0.0001).

The multivariable analysis (adjusted with propensity score) showed an independent association between proton pump inhibitor prescription and adverse events rates(cardiac death, AMI or ischemia driven revascularization) at 2 year follow up (HR 1.21; IC 95% 1.04–1.42; p=0.02).

Conclusion
In patients receiving clopidogrel after successful DES implantation, the concomitant indication of proton pump inhibitors was associated with high platelet reactivity and a higher rate of adverse events in the long term follow up.

Editorial Comment
Since inhibitors were indicated at physicians’ discretion, in order to compare such different populations a statistical adjustment is mandatory. This is why the lack of it stands as a limitation to study design and conclusive answers.