Differential antiplatelet effects of angiotensin converting enzyme inhibitors: comparison of ex vivo platelet aggregation in cardiovascular patients with ramipril, captopril and enalapril.
BACKGROUND
Increasing evidence suggests that angiotensin converting enzyme (ACE) inhibitors exert antithrombotic effects. Based on the assumption of differential effects of various ACE inhibitors on coagulation, the aim of the present study was to evaluate the coagulative activities of cardiovascular (CV) patients treated with either ramipril, captopril, and enalapril, and to compare these with patients treated with established antithrombotics such as aspirin (ASA) and clopidogrel or none of these medication.


METHODS
Blood samples of 320 CV patients with coronary artery disease and/or arterial hypertension were analyzed by wholeblood aggregometry. Platelet aggregation was determined by measuring the increase in impedance across paired electrodes in response to the aggregatory agents collagen and adenosine diphosphate (ADP), respectively. These data were correlated with medical treatment.


RESULTS
Platelet aggregation was attenuated ex vivo by ramipril and captopril as well as by ASA and clopidogrel. While collagen-induced platelet aggregation was significantly reduced by ramipril (35%; P <0.01) and captopril (27%; P = 0.01), no change was seen with enalapril. After induction with ADP, platelet aggregation was reduced in the presence of captopril therapy by 46% (P <0.05). There was a trend of inhibition with ramipril (32%, P = n.s.), whereas no antithrombotic effect was seen with enalapril.


CONCLUSIONS
Our findings demonstrate that ACE inhibitors decrease platelet aggregation ex vivo. The differential antiaggregatory profile may explain at least in part different effects of ACE inhibitors on cardiovascular endpoints as observed in large clinical trials.
Skowasch
Dirk
D
Department of Internal Medicine II, Cardiology, Heart Center University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. Dirk.Skowasch@ukb.uni-bonn.de
Viktor
Achim
A
Schneider-Schmitt
Melanie
M
Lüderitz
Berndt
B
Nickenig
Georg
G
Bauriedel
Gerhard
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D000077144:Clopidogrel; D003094:Collagen / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000503:physiopathology; D017097:Electric Impedance; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005858:Germany; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011446:Prospective Studies; D017257:Ramipril / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D004656:Enalapril; D003094:Collagen; D002216:Captopril; D000077144:Clopidogrel; D017257:Ramipril; D013988:Ticlopidine; D001241:Aspirin