Background-Platelet activation is a hallmark of acute coronary syndromes. Numerous lines of evidence suggest a mechanistic link between von Willebrand factor or platelet hyperfunction and myocardial damage in patients with acute coronary syndromes. Thus, we assessed whether platelet function under high shear rates (collagen adenosine diphosphate closure times [CADP-CTs]) measured with the platelet function analyzer (PFA-100) may be enhanced in patients with myocardial infarction (MI) and whether it may predict the extent of myocardial damage as measured by creatine kinase (CK-MB) or troponin T (TnT) levels. Methods and Results-Patients with acute chest pain or symptoms suggestive of acute coronary syndromes (nϭ216) were prospectively examined at an emergency department. CADP-CT was significantly shorter in patients with MI, particularly in those with an ST-segment-elevation MI (STEMI) compared with the other patient groups (unstable angina, stable coronary artery disease, or controls). Furthermore, CADP-CT and collagen epinephrine-CT at presentation were independent predictors of myocardial damage as measured by CK-MB or TnT. Patients with MI whose CADP-CT values fell in the first quartile had 3-fold higher CK-MB and TnT levels than those in the fourth quartile. Conclusions-Patients with STEMI have significantly enhanced platelet function when measured under high shear rates.CADP-CT is an independent predictor of the severity of MI, as measured by markers of cardiac necrosis. Measurement of platelet function with the PFA-100 may help in the risk stratification of patients presenting with MI. (Circulation.
See also Boos CJ, Lip GYH. Platelet activation and cardiovascular outcomes in acute coronary syndromes. This issue, pp 2542-3. Harrison P, Keeling D. Platelet hyperactivity and risk of recurrent thrombosis. This issue, pp 2544-6. Summary. Background: Platelet hyperfunction contributes to acute coronary syndromes (ACS). Thus, we hypothesized that platelet function under high shear stress predicts recurrent ACS during long-term follow-up of ACS patients. Patients and methods: Consecutive ACS patients (n ¼ 208) were prospectively followed-up for an average of 28 months. Platelet function was measured with the platelet function analyzer (PFA-100 Ò ; Dade Behring, Marburg, Germany) at baseline for collagen/adenosine diphosphate closure times (CADP-CT) and for collagen/epinephrine closure times (CEPI-CT) after infusion of a uniform dose of 250 mg aspirin. Results: Of the conventional risk factors, only the prevalence of diabetes was higher in ACS patients with re-events. However, use of clopidogrel and use of beta blockers were also slightly lower in patients with reevents (P < 0.05). The unadjusted risk hazard ratio (HR) for re-events was 3.3 [95% confidence interval (95% CI): 1.4-7.4; P ¼ 0.005] in those patients with the shortest CADP-CT values (lowest quartile). Similarly, the risk was 2.0-fold higher (95% CI: 1.1-3.6; P ¼ 0.02) in ACS patients with CEPI-CT < 300 s as compared with CEPI-CT ‡ 300 s. Inclusion of diabetes, clopidogrel and beta blockers in a multivariate Cox regression model enhanced the predictive value of CEPI-CT (HR: 2.7). Inclusion of von Willebrand factor levels did not alter the HR for recurrent ACS (HR: 2.1; 95% CI: 1.1-5.2; P ¼ 0.03) for CEPI-CT < 300 s, but reduced the HR for CADP-CT (HR: 2.8, 95% CI: 0.8-9.8; P ¼ 0.11). Conclusion: Shortened CT values reflect biologically relevant platelet hyperfunction in patients with ACS because they predict recurrent ACS.
Aspirin loading in the emergency room further reduced thromboxane B(2) levels and further inhibited platelet function in many patients with acute coronary syndrome already on 100 mg aspirin.
Background/Aims Little is known about the PD of clopidogrel in patients suffering from acute coronary syndromes (ACS) undergoing PCI. We hypothesized that the high degree of platelet activation in ACS patients may impede the PD effects of clopidogrel early after onset of ACS. Methods ACS patients (n=200), who presented to the University Hospital, were included into a prospective trial. Patients received a loading dose of clopidogrel (300 mg) followed by 75mg/d clopidogrel up to 12 months. Platelet function was assessed by the collagen adenosine diphosphate closure time (CAPD‐CT) with the FDA approved platelet function analyzer (PFA‐100). The single nucleotide polymorphism (SNP) i‐744 of the purinergic receptor P2Y12 was determined by Taqman technology. Results Baseline CAPD‐CT averaged 99s (CI: 90‐110), and a 10% increase in CADP‐CT was observed only after a time‐lag of 7 days (p=0.03). Maximum effectiveness was observed only after period of 3 months on therapy[CADP‐CT: 154s (138–169); p<0.0001]. The diagnosis of myocardial infarction and high plasma levels of von Willebrand Factor levels predicted decreased responsiveness to clopidogrel therapy, whereas the assessed P2Y12R SNP had no impact. Conclusions Our pharmacodynamic data indicate that ACS patients could profit from higher clopidogrel dosages particularly in the early weeks after PCI, and dose finding studies appear recommendable. Clinical Pharmacology & Therapeutics (2005) 77, P53–P53; doi:
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