Carolin Helten1, Philipp Mourikis1, Lisa Dannenberg1, René M'Pembele1, Kajetan Trojovsky1, Aysel Ayhan1, Christina Kohlmorgen2, Maria Grandoch2, Bodo Levkau3,4, Verena Veulemans1, Tobias Petzold5, Thomas Hohlfeld2, Malte Kelm1, Tobias Zeus1, Amin Polzin6,7. 1. Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Düsseldorf, Düsseldorf, Germany. 2. Institute of Pharmacology and Clinical Pharmacology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 3. Institute of Pathophysiology, West German Heart and Vascular Center, University Hospital Essen, Essen, Germany. 4. Institute of Molecular Medicine III, University Hospital Düsseldorf, Düsseldorf, Germany. 5. Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany. 6. Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Düsseldorf, Düsseldorf, Germany. Amin.Polzin@med.uni-duesseldorf.de. 7. Klinik für Kardiologie, Pneumologie und Angiologie, Universitätsklinikum Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany. Amin.Polzin@med.uni-duesseldorf.de.
Abstract
PURPOSE: ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are important drugs in cardiovascular disease. However, little is known about which of these drug class is to be preferred. First analyses show that the blockade of the renin-angiotensin-aldosterone system (RAAS) influences platelet reactivity. Therefore, we evaluated the effects of ACEI and ARB on platelet reactivity and thrombin generation. METHODS: We conducted a time series analysis in 34 patients. We performed light transmission aggregometry (LTA) to evaluate platelet reactivity. Results are given as maximum of aggregation (MoA). Thrombin generation was measured as endogenous thrombin potential (ETP) via calibrated automated thrombogram. Flow cytometry was used to analyze protease-activated receptor (PAR)-1 expression. RESULTS: ACEI treatment significantly increased platelet reactivity already 4 h after initiation of treatment (prior vs. 4 h post ACEI: MoA 41.9 ± 16.2% vs. 55.2 ± 16.7%; p = 0.003). After switching from ACEI to ARB treatment, platelet reactivity decreased significantly (3 months after switching: MoA 34.7 ± 20.9%; p = 0.03). ACEI reduced endogenous thrombin potential significantly from before to 3 months after ACEI (ETP 1527 ± 437 nM × min vs. 1088 ± 631 nM × min; p = 0.025). Platelet thrombin receptor (PAR1) expression increased from 37.38 ± 10.97% before to 49.53 ± 6.04% after ACEI treatment (p = 0.036). CONCLUSION: ACEI enhanced platelet reactivity. This can be reversed by changing to ARB. The mechanism behind RAAS influencing platelet function seems to be associated with PAR-1 expression.
PURPOSE:ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are important drugs in cardiovascular disease. However, little is known about which of these drug class is to be preferred. First analyses show that the blockade of the renin-angiotensin-aldosterone system (RAAS) influences platelet reactivity. Therefore, we evaluated the effects of ACEI and ARB on platelet reactivity and thrombin generation. METHODS: We conducted a time series analysis in 34 patients. We performed light transmission aggregometry (LTA) to evaluate platelet reactivity. Results are given as maximum of aggregation (MoA). Thrombin generation was measured as endogenous thrombin potential (ETP) via calibrated automated thrombogram. Flow cytometry was used to analyze protease-activated receptor (PAR)-1 expression. RESULTS: ACEI treatment significantly increased platelet reactivity already 4 h after initiation of treatment (prior vs. 4 h post ACEI: MoA 41.9 ± 16.2% vs. 55.2 ± 16.7%; p = 0.003). After switching from ACEI to ARB treatment, platelet reactivity decreased significantly (3 months after switching: MoA 34.7 ± 20.9%; p = 0.03). ACEI reduced endogenous thrombin potential significantly from before to 3 months after ACEI (ETP 1527 ± 437 nM × min vs. 1088 ± 631 nM × min; p = 0.025). Platelet thrombin receptor (PAR1) expression increased from 37.38 ± 10.97% before to 49.53 ± 6.04% after ACEI treatment (p = 0.036). CONCLUSION: ACEI enhanced platelet reactivity. This can be reversed by changing to ARB. The mechanism behind RAAS influencing platelet function seems to be associated with PAR-1 expression.
Authors: Maximilian Tscharre; Patricia P Wadowski; Constantin Weikert; Joseph Pultar; Beate Eichelberger; Simon Panzer; Thomas Gremmel Journal: Cardiovasc Drugs Ther Date: 2020-12-18 Impact factor: 3.727