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February 8, 2026European Heart Journal

Platelet reactivity of clopidogrel and aspirin with or without omeprazole in diabetes mellitus and coronary artery disease in thailand: a randomised double-blind placebo-controlled cross-over trial

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Why the study?

ESC guidelines recommend against concomitant omeprazole and clopidogrel due to drug interactions, but the combination remains widely used in resource-limited settings like Thailand, where its applicability is uncertain.

Does omeprazole increase platelet reactivity in diabetic patients with CAD on aspirin and clopidogrel?

Population

50 diabetic patients with CAD on aspirin and clopidogrel in Thailand

Comparison

Omeprazole 20 mg daily vs placebo

Design

Double-blind randomised placebo-controlled cross-over trial

Follow-up

two weeks per period

Key result

In diabetic CAD patients, Omeprazole increased mean PRU by 18.4 (10.2%, p=0.002) and raised Clopidogrel non-responders from 44% to 56%, with 25% responders becoming non-responders.

Authors

MTMetus ThungthienthongPVP VathesatogkitSKS Kluntang

Discussion

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Overview

Omeprazole should be avoided with clopidogrel in diabetic CAD; confirms interaction and extends evidence to this high-risk group.

Key Points

  • To evaluate the effect of Omeprazole on platelet reactivity in diabetic patients taking Clopidogrel and Aspirin.
  • Conducted a double-blind, randomised, placebo-controlled cross-over trial.
  • Involved diabetic patients with coronary artery disease on Clopidogrel and Aspirin.
  • Administered Omeprazole or placebo for two weeks, followed by a crossover period.
  • Measured platelet reactivity using the P2Y12 reaction units (PRU) assay at multiple time points.
  • Omeprazole increased mean PRU by 18.4 (10.2%, p = 0.002) compared to baseline.
  • The number of Clopidogrel non-responders rose from 44% to 56% after Omeprazole administration.
  • A higher BMI was associated with increased likelihood of being a non-responder (OR = 1.3, p = 0.02).

Structured PICO

Does omeprazole increase platelet reactivity in diabetic patients with CAD on aspirin and clopidogrel?

P
Population
50 diabetic patients with coronary artery disease (CAD) on Aspirin 81 mg/day and Clopidogrel 75 mg/day without Omeprazole for over two weeks. Age 67 years (IQR 60-67), 58% male. All had hypertension and dyslipidaemia.
I
Intervention
Omeprazole 20 mg daily for two weeks
C
Comparator
Placebo for two weeks
O
Outcome
Mean PRU (P2Y12 reaction units) change between Omeprazole and placebosurrogate

In diabetic patients with CAD, adding omeprazole to clopidogrel and aspirin significantly increases platelet reactivity and the rate of clopidogrel non-responders.

Cite This Study

Thungthienthong et al. (2025) studied this question. In diabetic CAD patients, Omeprazole increased mean PRU by 18.4 (10.2%, p=0.002) and raised Clopidogrel non-responders from 44% to 56%, with 25% responders becoming non-responders.

synapsesocial.com/papers/698827e20fc35cd7a8846e52https://doi.org/10.1093/eurheartj/ehaf784.4277
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