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- Title
Dose reduction, oral application, and order of intake to preserve aspirin antiplatelet effects in dipyrone co-medicated chronic artery disease patients.
- Authors
Dannenberg, Lisa; Petzold, Tobias; Achilles, Alina; Naguib, David; Zako, Saif; Helten, Carolin; M'Pembele, René; Mourikis, Philipp; Podsvyadek, Yanina; Grandoch, Maria; Levkau, Bodo; Zeus, Tobias; Kelm, Malte; Hohlfeld, Thomas; Polzin, Amin
- Abstract
Background: 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).Methods: 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.Results: 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).Conclusion: 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.
- Subjects
ARACHIDONIC acid; ASPIRIN; BLOOD platelets; CARDIOVASCULAR diseases risk factors; CORONARY disease; PEOPLE with diabetes; DRUG interactions; NONSTEROIDAL anti-inflammatory agents; OBESITY; ORAL drug administration; TIME; TIME series analysis; COMORBIDITY; DISEASE incidence; PHARMACODYNAMICS
- Publication
European Journal of Clinical Pharmacology, 2019, Vol 75, Issue 1, p13
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-018-2560-z