ABSTRACT
BACKGROUND: High platelet reactivity (HPR) under treatment with clopidogrel or aspirin is associated with adverse outcome. We aimed to investigate whether high platelet reactivity (HPR) to both aspirin and clopidogrel is a stronger predictor of adverse events compared to isolated HPR to clopidogrel or aspirin. METHODS: In this prospective cohort study platelet reactivity to adenosine diphosphate (ADP) and arachidonic acid (AA) was assessed by Multiple Electrode Aggregometry (MEA) in 403 patients undergoing percutaneous coronary intervention. The rates of the composite of cardiac adverse events (acute coronary syndrome, stent thrombosis, stroke, death and revascularization) were recorded during 12-month follow-up. RESULTS: The composite endpoint of cardiovascular adverse events occurred more often in patients with high platelet reactivity (HPR) to both agonists ADP and AA (37.5%) than in those with isolated HPR to ADP (33.3%), AA (25.6%) or without any HPR (18.6%; p=0.003). Classification tree analysis indicated that any HPR emerged as an independent predictor influencing outcome, which was associated with a 1.75 higher risk of cardiac adverse events (OR=1.75: 95%CI=1.1-2.9). Interestingly, the predictive value of HPR tended to be greater among patients with diabetes mellitus (OR=2.18; 95%CI=1.20-3.95). C-reactive protein and diabetes mellitus were independent predictors of high platelet reactivity to both agonists. CONCLUSIONS: Dual low responsiveness to clopidogrel and aspirin is a strong predictor of cardiac adverse events, especially in patients with diabetes mellitus, which underlines the need for personalized antiplatelet treatment.
Subject(s)
Aspirin/administration & dosage , Cardiovascular Diseases/blood , Cardiovascular Diseases/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation/physiology , Ticlopidine/analogs & derivatives , Aged , Cardiovascular Diseases/diagnosis , Clopidogrel , Cohort Studies , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Predictive Value of Tests , Prospective Studies , Ticlopidine/administration & dosage , Treatment OutcomeABSTRACT
A protective role against atherosclerosis can be attributed to angiotensin converting enzyme inhibitors (ACE-I), since they have been shown to reduce mortality in patients at cardiovascular risk. Since plasma levels of adhesion molecules are considered surrogate markers of endothelial cell activation and atherogenesis, we compared the levels of adhesion molecules after treatment with the ACE-I enalapril or the direct angiotensin- receptor antagonist losartan or placebo. In a randomized, controlled trial, 21 hypercholesterolemic volunteers received 50 mg/d losartan or 20 mg/d enalapril or placebo for twelve weeks. Plasma levels of circulating intercellular adhesion molecule-1 (cICAM-1), vascular adhesion molecule-1 (cVCAM-1), and E-selectin (cE-SEL) were measured by ELISA. Surface expression of ICAM-1 on circulating leukocytes was determined by flow cytometry. Enalapril and losartan but not placebo induced a small but stable decrease of cICAM-1 and cVCAM-1, while cE-SEL and leukocyte expression of ICAM-1 remained unchanged. The lowering of plasma adhesion molecules may indicate an antiatherogenic effect of angiotensin II blockade in hypercholesterolemia. While such preventive effect will have to be proven in clinical trials, our results do not support a preference for either enalapril or losartan with regard to their possible vasoprotective role.
