Platelet Inhibition with Cangrelor in Patients Undergoing PCI.
ABSTRACT Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y(12). This agent might have a role in the treatment of patients who require rapid, predictable, and profound but reversible platelet inhibition.
We performed a large-scale international trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The primary efficacy end point was a composite of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours.
We enrolled 8877 patients, and 8716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P=0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P=0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P=0.14).
Cangrelor, when administered intravenously 30 minutes before PCI and continued for 2 hours after PCI, was not superior to an oral loading dose of 600 mg of clopidogrel, administered 30 minutes before PCI, in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. (ClinicalTrials.gov number, NCT00305162.)
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ABSTRACT: Dual anti-platelet therapy, most commonly aspirin and clopidogrel, has been the standard of care for over a decade in patients who have experienced acute coronary syndrome, particularly when treated with coronary stenting. However, residual risk in patients receiving dual anti-platelet therapy post-acute coronary syndrome raises an unmet need for alternative therapy to clopidogrel. Consequently, novel anti-platelets agents including the P2Y12 receptor antagonists, such as prasugrel and ticagrelor, have emerged. Furthermore, using new methods to assess genetic polymorphisms and functional phenotypic assessments of platelet reactivity may become important in the development of personalized medicine and in developing tailored approaches to individual treatment. While robust large-scale evidence for genotypic- and phenotypic-guided therapy in improving outcomes is currently lacking, tremendous interest from various stakeholders including researchers, funding agencies, and industry continues to spur research endeavors in this arena. Further investigation is required in this emerging field to potentially offer improved platelet inhibition that may optimize cardioprotection and minimize bleeding risk in patients with acute coronary syndrome.Current Atherosclerosis Reports 05/2015; 17(5):501. DOI:10.1007/s11883-015-0501-1 · 3.06 Impact Factor
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ABSTRACT: Introduction: Dual antiplatelet therapy is the standard of care for patients with acute coronary syndromes or with recent coronary stents implantation. P2Y12 receptor antagonists have shown to reduce the risk of recurrent ischemic events among these patients, at the expense of an increased risk of bleeding. Cangrelor is a novel, intravenous, short-acting, reversible platelet P2Y12 inhibitor, which has been evaluated for the treatment of arterial thrombosis. Areas covered: Studies on the pharmacological characteristics of cangrelor and clinical trials were retrieved by a PubMed literature search. Expert opinion: Cangrelor has been tested in patients with coronary artery diseases undergoing percutaneous coronary intervention and as bridging therapy for patients undergoing coronary artery bypass graft. The rapid peak of action allows a fast and complete inhibition of platelet aggregation; the rapid offset is advantageous in case of bleeding complications; and finally, the intravenous administration also makes this drug suitable for patients unable to consume oral medications. Unfortunately, the large clinical trials evaluating cangrelor in percutaneous coronary intervention did not show superiority to the standard antiplatelet therapy, and its future use in this setting still needs to be better assessed. Conversely, when used as bridging therapy to coronary artery bypass graft, cangrelor showed promising results.Expert Opinion on Drug Metabolism & Toxicology 03/2015; 11(4):1-13. DOI:10.1517/17425255.2015.1021330 · 2.93 Impact Factor
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ABSTRACT: The efficacy and safety of new intravenous P2Y12 inhibitor (cangrelor) for patients with coronary artery disease (CAD) remain unclear. Trials were identified in PubMed, Web of Science, Embase, and Cochrane Database searches. We included four randomized, placebo-controlled reports in the meta-analysis. The database consisted of 36, 081 patients on cangrelor compared with clopidogrel or placebo. Major adverse cardiac events (MACE) were defined as the primary efficacy endpoint and major or severe bleeding at 48 hours was defined as the primary safety endpoint. Cangrelor significantly decreased risk of MACE (OR: 0.87, P = 0.002) and stent thrombosis (OR: 0.53, P < 0.001). However, at the same time, an increase in TIMI minor bleeding (OR: 1.49, P = 0.04) and in GUSTO moderate bleeding (OR: 1.43, P = 0.04) were observed by cangrelor. Intravenous administration of cangrelor is benefit to reduce risk of MACE and stent thrombosis in patients with CAD excepting for increased minor bleeding events.International Journal of Clinical and Experimental Medicine 01/2015; 8(1):800-8. · 1.42 Impact Factor