After Much Toing and Froing, Gastrointestinal Protection Is Back to the Forefront

Several clinical guidelines differ in their recommendation regarding the prescription of proton pump inhibitors to patients being treated with dual antiplatelet therapy after infarction. In 2015, the European Society of Cardiology (ESC) recommended their use in patients with high bleeding risk; however, in the 2017 update that recommendation became general after the assumption that, for all patients, the benefit outweighs the risk.

What would that risk be? Several studies proved an alteration in the pharmacokinetics of clopidogrel in patients who received proton pump inhibitors, but that never translated into clinical events.

Two things are clear: on the one hand, dual antiplatelet therapy reduces cardiovascular events after infarction; on the other, it increases the risk of bleeding.

Another thing is also clear: recurrent ischemic events and bleeding increase the mortality rate. However, the net clinical benefit favors use, particularly after acute myocardial infarction.

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The Clopidogrel and the Optimization of Gastrointestinal Events study showed that the use of proton pump inhibitors effectively reduces gastrointestinal bleeding, but the number of patients in this study with prior infarction was low, and the study only used aspirin + clopidogrel. Our knowledge of more powerful inhibitors such as prasugrel and ticagrelor is even more limited.

This study assessed 46,301 patients with dual antiplatelet therapy after acute myocardial infarction. Only 35% of patients (only those with higher risk of bleeding) were discharged with gastrointestinal protection.

At 1 year, the rate of upper gastrointestinal bleeding was 1% for the general population and 1.7% for high-risk patients.

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Globally, proton pump inhibitors were associated with a risk ratio (RR) of 0.62 (confidence interval [CI]: 0.48 to 0.77), corresponding to an absolute risk reduction of 0.44%. The RR for high-risk patients was similar to that of the general population: 0.47%.

Conclusion

Proton pump inhibitors are used less than recommended by clinical practice guidelines in Europe for patients who receive dual antiplatelet therapy after acute myocardial infarction. They effectively reduce the rate of upper gastrointestinal bleeding. Considering that the risk of bleeding is generally low, we should focus more on the identification of the patients who might benefit the most.

Original Title: Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction.

Reference: Thomas S.G. Sehested et al. European Heart Journal (2019) 00, 1–8. Article in press

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