P4556Thrombin generation and platelet function in patients on RAAS inhibitors

Abstract

Abstract Background ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are beneficial for patients with cardiovascular disease. However, little is known about whether one of these drugs is superior. First analyses show that the inhibition of the renin-angiotensin-aldosterone system (RAAS) affects platelet reactivity. Therefore we evaluated the effects of ACEI and ARB on platelet reactivity and thrombin generation. Methods In a time series analysis, samples of 24 patients before, 4h and 24h after initial intake of ACEI were analysed. Also we included 10 patients with permanent ACEI treatment and 4h, 24h and 3 months after switching to ARB. Platelet reactivity was measured via light transmission aggregometry (LTA). Thrombin generation was measured as endogenous thrombin potential (ETP) by calibrated automated thrombogram. Protease-activated receptor (PAR) expression was analysed by flow cytometry. Thrombin-antithrombin (TAT) complexes were measured with an enzyme-linked immunosorbent assay. Results TRAP-6 induced platelet reactivity increased during ACEI treatment (prior vs. 4h post ACEI: 41.9±16.2% vs. 55.2±16.7%; p=0.003, prior vs. 24h post ACEI: 52.3±12.7%; p=0.003). Switching from chronic ACEI to ARB treatment decreased platelet reactivity (permanent ACEI vs. 3 months after switching: 50.3±20.9% vs. 34.7±20.9%; p=0.033). ACEI reduced ETP from prior to 3 months post ACEI (1527±437 nM*min vs. 1088±631 nM*min; p=0.025). ARB did not affect ETP (1526±587 nM*min vs. 1369±516 nM*min; p=0.3). PAR1 levels rose from 37.38±10.97% before to 49.53±6.04% after ACEI treatment (p=0.036). ARB did not have an effect on PAR1 (33.16±11.73 vs. 32.86±8.99; p=0.89). ACEI slightly decreased plasma thrombin concentration. ARB treatment showed a minor but again not significant decrease in TAT complexes as well. (TAT complexes prior vs. 3 months post ACEI: 8.4±11.9 μg/l vs. 6.3±6.8 μg/l; p=0.99, permanent ACEI vs. 3 months after switching to ARB: 4.3±1.9 μg/l vs. 3.0±1.0 μg/l; p=0.3). Conclusion ACEI increased platelet reactivity. This can be reversed by switching to ARB. The mechanism behind RAAS influencing platelet function needs to be further investigated in larger trials. Acknowledgement/Funding Medical Faculty of the Heinrich-Heine-University Düsseldorf