We Need Further Studies for the Development of "Optimized Antiplatelet Therapy" Based on Ethnicity

Journal of the American College of Cardiology (Impact Factor: 15.34). 07/2011; 58(2):198; author reply 198-9. DOI: 10.1016/j.jacc.2011.02.048
Source: PubMed


Available from: Kevin P Bliden, May 22, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined. To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days. At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001). Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. Identifier: NCT00645918.
    JAMA The Journal of the American Medical Association 03/2011; 305(11):1097-105. DOI:10.1001/jama.2011.290 · 30.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to test whether cilostazol has beneficial effects in the real-world patients treated with intracoronary drug-eluting stents (DES). The addition of cilostazol on the conventional dual antiplatelet therapy has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention in previous studies. In a randomized multicenter trial, we enrolled 960 patients who received DES. They were randomized to receive either dual antiplatelet therapy (DAT) (aspirin and clopidogrel) or triple antiplatelet therapy (TAT) (aspirin, clopidogrel, and cilostazol) for 6 months. Primary end point was the composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization (TLR). Secondary end points were P2Y₁₂ reaction unit (PRU) measured with the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) at discharge and at 6 months after the index procedure. All-cause death, stent thrombosis, and each component of the primary end point at 6 months were other secondary end points. Analysis was done on an intention-to-treat basis. At 6 months' follow-up, there was no difference in the primary end point between the 2 groups (8.5% in TAT vs. 9.2% in DAT, p = 0.74). In secondary end point analysis, the TAT group achieved lower PRU levels than the DAT group both at discharge (206.6 ± 90.3 PRU vs. 232.2 ± 80.3 PRU, p < 0.001) and at 6 months (210.7 ± 87.9 PRU vs. 255.7 ± 73.7 PRU, p < 0.001). In the Cox proportional hazards analysis, lesion length (≥28 mm, hazard ratio [HR]: 2.10, 95% confidence interval [CI]: 1.25 to 3.52), and PRU level at discharge (every increase in tertile, HR: 1.61, 95% CI: 1.16 to 2.25) were predictors of the primary end point, but not the use of cilostazol (HR: 0.90, 95% CI: 0.54 to 1.52). Despite the greater reduction of platelet reactivity by addition of cilostazol to conventional DAT, TAT did not show superiority in reducing the composite of adverse cardiovascular outcomes after DES implantation. (The Efficacy of CILostazol ON Ischemic Complications After DES Implantation [CILON-T]; NCT00776828).
    Journal of the American College of Cardiology 01/2011; 57(3):280-9. DOI:10.1016/j.jacc.2010.08.631 · 15.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate whether adenosine diphosphate (ADP)-derived adenosine might inhibit platelet aggregation, especially in the presence of a P2Y₁₂ antagonist, where the effects of ADP at the P2Y₁₂ receptor would be prevented. Platelet aggregation was measured in response to thrombin receptor activator peptide by platelet counting in platelet-rich plasma (PRP) and whole blood in the presence of ADP and the P2Y₁₂ antagonists cangrelor, prasugrel active metabolite, and ticagrelor. In the presence of a P2Y₁₂ antagonist, preincubation of PRP with ADP inhibited aggregation; this effect was abolished by adenosine deaminase. No inhibition of aggregation occurred in whole blood except when dipyridamole was added to inhibit adenosine uptake into erythrocytes. The effects of ADP in PRP and whole blood were replicated using adenosine and were directly related to changes in cAMP (assessed by vasodilator-stimulated phosphoprotein phosphorylation). All results were the same irrespective of the P2Y₁₂ antagonist used. ADP inhibits platelet aggregation in the presence of a P2Y₁₂ antagonist through conversion to adenosine. Inhibition occurs in PRP but not in whole blood except when adenosine uptake is inhibited. None of the P2Y₁₂ antagonists studied replicated the effects of dipyridamole in the experiments that were performed.
    Arteriosclerosis Thrombosis and Vascular Biology 02/2011; 31(2):416-22. DOI:10.1161/ATVBAHA.110.219501 · 5.53 Impact Factor