[Proton pump inhibitors and clopidogrel: an association to avoid?].

Dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular events following an acute coronary syndrome or stent implantation, but the associated increased risk of gastrointestinal bleeding often leads clinicians to the co-administration of proton pump inhibitors (PPIs). PPIs have been shown to decrease antiplatelet effects of clopidogrel ex vivo, raising doubts on the safety of this drug combination. Clinical trials investigating PPI-clopidogrel interaction have provided conflicting results and have been often criticized. Moreover, a prospective, double-bind, randomized, placebo-controlled study conducted with adequate follow-up and sample size has not yet been performed. Indeed, the COGENT trial, which would have had such characteristics, has been stopped prematurely. The question is therefore still unresolved, and clinical effects of PPI-clopidogrel interaction cannot be excluded. As a practical consequence, this combination therapy is recommended only for patients at high risk of bleeding (prior upper gastrointestinal bleeding, advanced age, concomitant use of warfarin, steroidal or non-steroidal anti-inflammatory drugs and Helicobacter pylori infection), avoiding in any case PPIs with greater affinity for CYP2C19, such as omeprazole and esomeprazole.

RCT Entities:   Population Interventions Outcomes