Dose reduction, oral application, and order of intake to preserve aspirin antiplatelet effects in dipyrone co-medicated chronic artery disease patients
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Dipyrone comedication in aspirin-treated patients is associated with impaired pharmacodynamic response to aspirin (high on-treatment platelet reactivity [HTPR]). Additionally, in small observational studies, an association with impaired outcome has been described. In this uncontrolled, hypothesis-generating study, we aimed to investigate strategies to prevent this drug-drug interaction in patients with coronary artery disease (CAD).
We analyzed pharmacodynamic response to aspirin in 80 dipyrone co-medicated CAD patients. Aspirin antiplatelet effects were measured using arachidonic acid (AA)-induced light-transmission aggregometry (LTA). Platelet reactivity was associated with daily dose, administration form, and frequency. Additionally, we conducted a time-series analysis in patients with HTPR to aspirin with re-evaluation of pharmacodynamic response to aspirin after 5 days.
Patients’ mean age was 75.5 ± 9.8 years. Forty-three (54%) were male, 22 (27.5%) obese, and 38 (47.5%) diabetics. Baseline characteristics, cardiovascular risk factors, comorbidities, comedication, or laboratory parameters did not differ between patients with or without HTPR. HTPR to aspirin occurred in 34 out of 80 patients (42.5%). The incidence of HTPR was associated with dipyrone daily dose (< 1 g/day: HTPR 20% vs. > 3 g/day: HTPR 50%, p > 0.0001) and form of administration (i.v. 87.5% vs. oral 37.5%; p < 0.0001). A strict order of intake (aspirin 30 min prior to dipyrone) restored aspirin antiplatelet effects in all patients (HTPR before 100% vs. HTPR after 0%, p = 0.0002).
This study shows that dipyrone should be used with caution in aspirin-treated patients. If dipyrone seems indispensable, the lowest effective dose and a strict order of intake seem favorable.
KeywordsAggregation Aspirin Comedication Dipyrone Platelet activation Platelet inhibition
Angiotensine converting enzyme
- AT II
Coronary bypass grafting
Chronic obstructive pulmonary disease
Chronic artery disease
Chronic kidney disease
Glomerular filtration rate
High density lipoprotein
High on-treatment platelet reactivity
Light transmission aggregometry
Major adverse cardiac and cerebrovascular events
Maximum of aggregation
Percutaneous coronary intervention
The authors thank Kirsten Bartkowski for experimental support.
L.D., T.P., and A.A. designed the study, analyzed, and interpreted data and wrote the manuscript. D.N., S.Z., C.H., R.M., and P.M. collected data and revised the manuscript. A.P., T.H., M.K., T.Z., B.L., M.G., and Y.P. supervised the study and revised the manuscript.
This work was supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University (No. 46-2016, to L.D., No. 16-2014 to A.P.).
Compliance with ethical standards
The study conformed to the Declaration of Helsinki and was approved by the University of Düsseldorf Ethics Committee.
Conflict of interest
The authors declare that they have no conflicts of interest.
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