Cangrelor increases the magnitude of platelet inhibition and reduces interindividual variability in clopidogrel-pretreated subjects

Bouman, H. J.; Werkum, Jochem W. van; Hackeng, Christian M.; Clappers, Nick; Berg, J M Ten

doi:10.1007/bf03086246

Cited by 9 publications

(5 citation statements)

References 13 publications

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“…The present study provides a rationale for the administration of a fortified antiplatelet treatment in CYP2C19*2 carriers scheduled for PCI, and information provided by platelet 20 and newer agents such as ticagrelor 21 or cangrelor 22 may be potent treatment options for high-risk patients. Several drugs, including statins, 23 omeprazole 24 and calcium-channel blockers, 25 can decrease the effect of clopidogrel on platelet activation.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Cytochrome P450 2C19^*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel

et al. 2011

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This study investigated the relationship between the cytochrome P450 2C19 (CYP2C19) *2 polymorphism (681A) and definite stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel (75 mg/day, orally). The CYP2C19*2 polymorphism status of 1738 Chinese patients with coronary artery disease was examined. The primary endpoint was the occurrence of definite ST during the 180-day follow-up period. The presence of at least one CYP2C19*2 allele was significantly associated with increased ST risk (19 CYP2C19*2/*2 or *1/*2 patients [2.4%] versus seven homozygous wild-type CYP2C19*1/*1 patients [0.75%]). The risk of definite ST was highest in patients with the CYP2C19*2/*2 genotype. The CYP2C19*2 genotype is associated with an increased risk of definite ST following coronary stent placement among Chinese patients with coronary artery disease receiving clopidogrel.

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Section: Discussionmentioning

confidence: 99%

Relationship between Cytochrome P450 2C19^*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel

et al. 2011

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“…114,115 In a preclinical study, the in vitro addition of cangrelor to platelet-rich plasma of clopidogrel-pretreated patients enhanced the reduction in ADP-induced platelet aggregation. 116 Moreover, cangrelor diminished the interindividual variation observed in clopidogrel-inhibited platelet aggregation. 116 In a phase II trial in patients undergoing PCI, cangrelor exhibited a dose-dependant platelet inhibition similar to that of abciximab (a GPIIb/IIIa inhibitor), a smaller prolongation of bleeding time, and a more rapid return to baseline platelet function.…”

Section: Adenosine Triphosphate Analogsmentioning

confidence: 96%

“…116 Moreover, cangrelor diminished the interindividual variation observed in clopidogrel-inhibited platelet aggregation. 116 In a phase II trial in patients undergoing PCI, cangrelor exhibited a dose-dependant platelet inhibition similar to that of abciximab (a GPIIb/IIIa inhibitor), a smaller prolongation of bleeding time, and a more rapid return to baseline platelet function. 114 The phase III Cangrelor Versus Standard Therapy to achieve Optimal Management of Platelet Inhibition program (CHAM-PION) trials 117,118 assessed the safety and efficacy of cangrelor for the prevention of all-cause death, acute MI, and ischemic events in patients with ACS scheduled for PCI, compared with clopidogrel and placebo.…”

Section: Adenosine Triphosphate Analogsmentioning

confidence: 96%

Review: Antiplatelet Drugs: What Comes Next?

Kei

Florentin

Mikhailidis

et al. 2010

Clin Appl Thromb Hemost

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Antiplatelet drugs are important components in the management of atherothrombotic vascular disease. However, several limitations restrict the safety and efficacy of current antiplatelet therapy in clinical practice. Interpatient variability and resistance to aspirin and/or clopidogrel has spurred efforts for the development of novel agents. Indeed, several antiplatelet drugs are at various stages of evaluation; those at advanced stage of development are the focus of this review.

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“…In an in vitro study, when cangrelor was added to the platelet-rich plasma of clopidogrel-pretreated patients, it resulted in further platelet inhibition. 51 In patients on prasugrel maintenance therapy, in vitro incubation with cangrelor provided more rapid than prasugrel reloading platelet inhibition. 52 Furthermore, maintenance treatment with ticagrelor for 5 days did not affect the inhibitory effects of cangrelor.…”

Section: Unsettled Issuesmentioning

confidence: 99%

Cangrelor in Percutaneous Coronary Intervention: Current Status and Perspectives

Alexopoulos

Pappas

Sfantou

et al. 2017

J Cardiovasc Pharmacol Ther

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Cangrelor is an intravenously administered P2Y receptor antagonist with very fast, potent, and quickly reversible action. In the CHAMPION PHOENIX trial, cangrelor provided an improved anti-ischemic protection compared with clopidogrel, without increasing the risk of severe bleeding. Cangrelor is currently approved by drug regulating authorities for patients undergoing percutaneous coronary intervention (PCI) without prior treatment with a P2Y receptor antagonist and not receiving a glycoprotein IIb/IIIa inhibitor, while its use is endorsed with a class IIb recommendation by the European Society of Cardiology guidelines. Several subanalyses of CHAMPION PHOENIX trial have tried to elucidate the role of cangrelor in PCI, including its usefulness during a 2-hour landmark analysis, impact on intraprocedural stent thrombosis, and reduction in myocardial infarction (MI) rate. The influence of gender, geographic region, access site, and bivalirudin use on cangrelor's effects has also been reported. In patients with ST elevation MI and in clinical scenarios of disturbed absorption of oral antiplatelet agents or in need of an intravenous agent, cangrelor may surpass oral agents' drawbacks. Transitioning to an oral agent is mandatory following cangrelor infusion discontinuation, although ticagrelor may be administered earlier without any pharmacodynamic interaction. Nevertheless, the clinical role of cangrelor in conjunction with administration of prasugrel or ticagrelor remains unclear. Accruing real-life experience is expected to improve our understanding of cangrelor's role in everyday clinical practice.

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Cangrelor increases the magnitude of platelet inhibition and reduces interindividual variability in clopidogrel-pretreated subjects

Cited by 9 publications

References 13 publications

Relationship between Cytochrome P450 2C19^*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel

Relationship between Cytochrome P450 2C19^*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel

Review: Antiplatelet Drugs: What Comes Next?

Cangrelor in Percutaneous Coronary Intervention: Current Status and Perspectives

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Cangrelor increases the magnitude of platelet inhibition and reduces interindividual variability in clopidogrel-pretreated subjects

Cited by 9 publications

References 13 publications

Relationship between Cytochrome P450 2C19*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel

Relationship between Cytochrome P450 2C19*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel

Review: Antiplatelet Drugs: What Comes Next?

Cangrelor in Percutaneous Coronary Intervention: Current Status and Perspectives

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Relationship between Cytochrome P450 2C19^*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel

Relationship between Cytochrome P450 2C19^*2 Polymorphism and Stent Thrombosis following Percutaneous Coronary Intervention in Chinese Patients Receiving Clopidogrel