Key result
Concomitant use of various proton pump inhibitors with clopidogrel did not significantly change platelet aggregation compared to clopidogrel alone (0.53 ohms of resistance) in healthy volunteers.
Why the study?
Does the addition of proton pump inhibitors to clopidogrel affect platelet aggregation in healthy volunteers?
RCT (n=22)
incomplete crossover design
Does the addition of proton pump inhibitors to clopidogrel affect platelet aggregation in healthy volunteers?
In young healthy volunteers with a robust response to clopidogrel, the concomitant use of various proton pump inhibitors does not significantly affect clopidogrel's antiplatelet effect as measured by whole blood aggregation.
Supports concomitant PPI-clopidogrel use without compromising antiplatelet effect; confirms neutral interaction across PPIs in healthy volunteers.
OBJECTIVE: The present data examines the response to clopidogrel 75 mg daily as measured by ADP 10µM induced whole blood aggregation (WBA) in participants on clopidogrel alone and then in combination with pantoprazole 40 mg, omeprazole 20 mg, rabeprazole 20 mg, esomeprazole 40 mg, lansoprazole 30 mg, or dexlansoprazole 30 mg. BACKGROUND: The CYP enzyme system is essential for the conversion of clopidogrel into its active metabolite. This system is also responsible for metabolizing proton pump inhibitors (PPIs) which are frequently used concomitantly and uniquely inhibit different combinations of CYP enzymes to varying degrees. METHDOS: Twenty-two participants, mean age 24.62±3.46, were randomized to an incomplete crossover design schedule and underwent WBA testing at drug free baseline, after clopidogrel run-in, while on clopidogrel in combination with 1 of 3 PPIs, and during 1 week washout periods between PPIs. Participants were excluded if they did not aggregate at drug free baseline, lacked antiplatelet effect from clopidogrel (>6 ohms of resistance), or if weekly pill counts showed <80[percnt] compliance. RESULTS: The mean aggregation to ADP at the drug free baseline was 10.58±2.17 ohms of resistance and decreased to 0.53±1.26 ohms of resistance on clopidogrel alone. Ohms of resistance did not significantly change between concomitant use of PPIs and clopidogrel alone or between PPIs: pantoprazole 1.29±3.40, omeprazole 1.50±2.45, rabeprazole 1.63±3.16, esomeprazole 0.78±1.10, dexlansoprazole 0.75±1.49, and lansoprazole 0.50±1.41. CONCLUSIONS: These data do not demonstrate a significant interaction between commonly prescribed PPIs and clopidogrel in healthy volunteers with a robust response to clopidogrel alone. This is the first study to compare all available PPIs head-to-head. The results of this study suggest that in younger individuals who have a robust response to clopidogrel and do not have other interacting medications, the addition of a PPI may have a negligible effect on clopidogrel response.
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Gengo et al. (2015) conducted an RCT in Healthy volunteers (n=22). Proton pump inhibitors (PPIs) added to clopidogrel vs. Clopidogrel alone was evaluated on ADP 10µM induced whole blood aggregation (WBA) in ohms of resistance. Concomitant use of various proton pump inhibitors with clopidogrel did not significantly change platelet aggregation compared to clopidogrel alone (0.53 ohms of resistance) in healthy volunteers.
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