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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 D Kristensen1,
  4. Anne-Mette Hvas2
  1. 1Department of Cardiology, Aarhus University Hospital, Skejby, Denmark
  2. 2Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
  1. Correspondence to Dr Anne-Mette Hvas, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, 8200 Aarhus N, 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 patients with CAD, 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 (Dynabyte, Munich, Germany) 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 treatment 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% CI 0.96 to 1.72) vs 0.92 (0.84 to 1.01) ng/ml, p=0.01).

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

  • Aspirin
  • coronary artery disease
  • drug interactions
  • platelet aggregation
  • proton pump inhibitors
  • antiplatelet treatment
  • AU
  • aggregation unit(s)
  • CAD
  • coronary artery disease
  • CYP
  • cytochrome P450
  • IQR
  • interquartile range
  • PPI(s)
  • proton pump inhibitor(s)
  • sP-selectin
  • soluble serum P-selectin
  • S-TxB2
  • serum thromboxane B2

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  • Funding The study was supported by the Danish Research Agency (grant 2101-05-0052 to MW, ELG and SDK).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the the Central Denmark Region Committees on Biomedical Research Ethics.

  • Provenance and peer review Not commissioned; externally peer reviewed.