Antiplatelet effects of angiotensin-converting enzyme inhibitors compared with aspirin and clopidogrel: a pilot study with whole-blood aggregometry.
BACKGROUND
Although specific antiplatelet drugs are well-established and effective in atherosclerosis prevention, recent clinical trials have also shown that use of angiotensin-converting enzyme (ACE) inhibitors results in a decrease in cardiovascular events. Therefore, in this study, we sought to assess the coagulative activity of patients with cardiovascular disease grouped for treatment with either ACE inhibitors, aspirin, clopidogrel/aspirin, or none of these medications.


METHODS
Blood samples from 303 patients with cardiovascular disease were analyzed with whole-blood aggregometry. Platelet aggregation was determined by the increase in impedance across paired electrodes in response to the aggregatory agents adenosine diphosphate (ADP) or collagen.


RESULTS
As the central finding, platelet aggregation was attenuated by ACE inhibitors and by aspirin or clopidogrel/aspirin, which was indicated by a lower impedance increase compared with no medication. With ACE inhibition, platelet aggregation decreased by 33% (P =.042) after ADP induction. No significant antithrombotic effect was seen with aspirin alone (17%, P = 1.0), whereas a decrease in ADP-induced platelet aggregation was extensive with clopidogrel/aspirin (85%, P =.001). After collagen induction, platelet aggregation was reduced by 16% (P =.028) in the presence of ACE inhibitor therapy, whereas inhibition with aspirin and clopidogrel/aspirin was 23% (P =.004) and 35% (P =.026), respectively, compared with participants who were not treated.


CONCLUSIONS
These ex vivo data on whole-blood aggregometry provide direct evidence that ACE inhibitors decrease platelet aggregation, whereas aspirin and clopidogrel are confirmed as established antithrombotics. Pleiotropic effects of ACE inhibition on platelet function may contribute to the clinical benefit observed with this drug class on major cardiovascular end points.
Bauriedel
Gerhard
G
Department of Cardiology, Heart Center, University of Bonn, Bonn, Germany. Gerhard.Bauriedel@ukb.uni-bonn.de
Skowasch
Dirk
D
Schneider
Melanie
M
Andrié
René
R
Jabs
Alexander
A
Lüderitz
Berndt
B
D000244:Adenosine Diphosphate / Q000627:therapeutic use; D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D016022:Case-Control Studies; D000077144:Clopidogrel; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin