The antiplatelet effect of aspirin is reduced by proton pump inhibitors in patients with coronary artery disease.
OBJECTIVE
To evaluate the effect of proton pump inhibitors (PPIs) on the platelet response to aspirin in patients with coronary artery disease (CAD).


METHODS
Case-control study.


METHODS
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.


METHODS
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 B(2) 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 B(2) 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 B(2) 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.
Würtz
Morten
M
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Grove
Erik L
EL
Kristensen
Steen D
SD
Hvas
Anne-Mette
AM
D000368:Aged; D001241:Aspirin / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012042:Registries; D013929:Thromboxane B2 / Q000097:blood
D015415:Biomarkers; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D013929:Thromboxane B2; D001241:Aspirin