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The Antiplatelet Effect of Aspirin is Reduced by Proton Pump Inhibitors in Patients With Coronary Artery Disease
  1. Morten Würtz1,
  2. Erik L Grove1,
  3. Steen Dalby Kristensen1,
  4. Anne-Mette Hvas2,*
  1. 1 Department of Cardiology, Aarhus University Hospital, Skejby, Denmark, Denmark;
  2. 2 Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark, Denmark
  1. Correspondence to: Anne-Mette Hvas, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark, Brendstrupgaardsvej 100, Skejby, Aarhus, 8200, Denmark; am.hvas{at}


Objective: To evaluate the effect of proton pump inhibitors (PPIs) on the platelet response to aspirin in patients with coronary artery disease (CAD).

Design: Case-control study.

Patients: 418 stable CAD patients, 54 of whom were treated with PPIs. All patients were treated with non-enteric coated aspirin 75 mg/day and received no other antithrombotic drugs.

Main outcome measures: Platelet aggregation was measured by Multiplate® whole blood aggregometry induced by arachidonic acid 1.0 mmol/L and expressed as area under the aggregation curve (Aggregation Units*min). Platelet activation was assessed by soluble serum P-selectin. Compliance was confirmed by serum thromboxane B2 levels.

Results: The distribution of age, sex, body mass index, blood pressure, family history of ischaemic heart disease, smoking, diabetes, and the number of previous ischaemic events did not differ between groups. All patients were compliant with aspirin therapy according to serum thromboxane B2 levels. Platelet aggregation (median 180 (interquartile range 119-312) vs. 152 (84-226) Aggregation Units*min, p = 0.003) and soluble serum P-selectin levels (88.5 (65.2-105.8) vs. 75.4 (60.0-91.5) ng/mL, p = 0.005) were significantly higher in patients treated with PPIs. Furthermore, these patients had significantly higher serum thromboxane B2 levels (geometric mean 1.29 (95% confidence interval 0.96-1.72) vs. 0.92 (0.84-1.01) ng/mL, p = 0.011).

Conclusions: CAD patients treated with PPIs had a reduced platelet response to aspirin in terms of increased residual platelet aggregation and activation compared with CAD patients not taking PPIs. Concomitant use of aspirin and PPIs might reduce the cardiovascular protection by aspirin.

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