Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 6;10(13):e022125.
doi: 10.1161/JAHA.121.022125. Epub 2021 Jul 2.

Cangrelor: Clinical Data, Contemporary Use, and Future Perspectives

Leonardo De Luca  1 , Philippe Gabriel Steg  2   3 , Deepak L Bhatt  4 , Davide Capodanno  5 , Dominick J Angiolillo  6
Affiliations
Review

Cangrelor: Clinical Data, Contemporary Use, and Future Perspectives

Leonardo De Luca et al. J Am Heart Assoc. .

Abstract

Cangrelor is the only currently available intravenous platelet P2Y12 receptor inhibitor. It is characterized by potent, predictable, and rapidly reversible antiplatelet effects. Cangrelor has been tested in the large CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program, where it was compared with different clopidogrel regimens, and it is currently indicated for use in patients with coronary artery disease undergoing percutaneous coronary intervention. However, the uptake of cangrelor use varies across the globe and may also include patients with profiles different from those enrolled in the registration trials. These observations underscore the need to fully examine the safety and efficacy of cangrelor in postregistration studies. There are several ongoing and planned studies evaluating the use of cangrelor in real-world practice which will provide important insights to this extent. The current article provides a review on the pharmacology, clinical studies, contemporary use of cangrelor in real-world practice, a description of ongoing studies, and futuristic insights on potential strategies on how to improve outcomes of patients undergoing percutaneous coronary intervention.

Keywords: acute coronary syndromes; cangrelor; percutaneous coronary intervention.

PubMed Disclaimer

Conflict of interest statement

Dr De Luca declares that he has received consulting fees or honoraria from Amgen, Aspen, AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Daiichi Sankyo, Eli Lilly, Menarini, Pfizer/Bristol‐Myers Squibb, Sanofi, Servier, and The Medicines Company, outside the present work; Dr Steg declares that he has received consulting fees or honoraria from Amgen, Myokardia, Novo‐Nordisk, and Regeneron, and has received research grants from Amarin, Bayer, Sanofi, and Servier, outside the present work; he has also received payments for participation in clinical trials (Steering Committee, Clinical Events Committee [CEC], Data Safety Monitoring Board [DSMB]) of Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Idorsia, Novartis, Pfizer, Sanofi, and Servier. Dr Bhatt discloses the following relationships: Advisory Board: Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, MyoKardia, PhaseBio, PLx Pharma, and Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED [CENTERA THV System in Intermediate Risk Patients Who Have Symptomatic, Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement] trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE‐II [Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE [Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation] trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (ACC) (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice‐Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE‐DUAL PCI [Evaluation of Dual Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting] clinical trial steering committee funded by Boehringer Ingelheim; AEGIS‐II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE [A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease] trial, funded by Ferring Pharmaceuticals), HMP Global (Editor‐in‐Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co‐Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies] operations committee, publications committee, steering committee, and US national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR (National Cardiovascular Data Registry)‐ACTION (Acute Coronary Treatment and Intervention Outcomes) Registry Steering Committee (Chair), Veterans Affairs Clinical Assessment Reporting and Tracking (VA CART) Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Cardax, Chiesi (including for his role as co‐Chair of CHAMPION PHOENIX), CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, MyoKardia, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company (including for his role as co‐Chair of the CHAMPION trials); Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co‐Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, and Takeda. Dr Capodanno declares that he has received consulting fees or honoraria from AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Daiichi‐Sankyo, and Sanofi, outside the present work; Dr Angiolillo declares that he has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol‐Myers Squibb, Chiesi, Daiichi‐Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company, and has received payments for participation in review activities from CeloNova and St. Jude Medical, outside the present work. Dr Angiolillo also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi‐Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation.

Figures

Figure 1
Figure 1. Mechanism of action of oral and intravenous P2Y12 inhibitors on platelet receptors (A) and transition to oral platelet P2Y12 receptor inhibitors in cangrelor‐treated patients (B).
CAD indicates coronary artery disease; CYP, cytochrome P450; PCI, percutaneous coronary intervention; and PLT, platelet.
Figure 2
Figure 2. Clinical results of the CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) PHOENIX trial.
GUSTO indicates Global Use of Strategies to Open Occluded Coronary Arteries; IDR, ischemia‐driven revascularization; MI, myocardial infarction; mITT, modified intention‐to‐treat; NSTE‐ACS, non–ST‐segment–elevation acute coronary syndrome; OR, odds ratio; PCI, percutaneous coronary intervention; ST, stent thrombosis; and STEMI, ST‐segment–elevation myocardial infarction.
Figure 3
Figure 3. Use of cangrelor in patients with acute coronary syndrome (ACS).
MI indicates myocardial infarction; NSTEMI, non–ST‐segment–elevation myocardial infarction; OS, oral somministration; PCI, percutaneous coronary intervention; and STEMI, ST‐segment–elevation myocardial infarction.
Figure 4
Figure 4. Design of the ARCANGELO (Italian Prospective Study on Cangrelor).
Each letter (A, B, C, and D) represents a patient prototype. Orange boxes identified the Informed and Privacy Consent Form. Green diamonds identify time of discharge. Each horizontal solid line represents the period of observation of each patient, which can be either mainly entirely prospective (orange lines) or could also include, for a small proportion of patients, a retrospective period (blue lines). Cangrelor intravenous infusion could end after percutaneous coronary intervention (PCI) conclusion. Even if adherence to European Medical Agency indications is not required, the transition to oral platelet P2Y12 receptor inhibitors may occur before the end of cangrelor infusion, according to the product's approved summary of product characteristics (SPC). In these examples, patients A and B were both eligible, because the Informed and Privacy Consent Form was signed before patient discharge; in particular, patient B was not able to give consent before start of cangrelor and PCI. On the contrary, patient C provided consent after being discharged; therefore, the patient was not eligible. Also, patient D was not eligible because death occurred before being able to obtain Informed and Privacy Consent Form. ACS indicates acute coronary syndrome; BARC, Bleeding Academic Research Consortium; FPFV, first patient first visit; MACE, major adverse cardiac event; and pts, patients.
Figure 5
Figure 5. Antithrombotic drugs currently developed for the treatment of acute coronary syndrome.
GP indicates glycoprotein; PAR, protease‐activated receptors; and PDI, protein disulfide isomerase.
See this image and copyright information in PMC

References

    1. Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circ J. 2010;74:597–607. DOI: 10.1253/circj.CJ-09-0982. - DOI - PubMed
    1. Damman P, Woudstra P, Kuijt WJ, De Winter RJ, James SK. P2Y12 platelet inhibition in clinical practice. J Thromb Thrombolysis. 2012;33:143–153. DOI: 10.1007/s11239-011-0667-5. - DOI - PMC - PubMed
    1. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ. ACC/AHA versus ESC guidelines on dual antiplatelet therapy: JACC guideline comparison. J Am Coll Cardiol. 2018;72:2915–2931. DOI: 10.1016/j.jacc.2018.09.057. - DOI - PubMed
    1. De Luca L, Leonardi S, Cavallini C, Lucci D, Musumeci G, Caporale R, Abrignani MG, Lupi A, Rakar S, Gulizia MM, et al. Contemporary antithrombotic strategies in patients with acute coronary syndrome admitted to cardiac care units in Italy: the EYESHOT Study. Eur Heart J Acute Cardiovasc Care. 2015;4:441–452. DOI: 10.1177/2048872614560505. - DOI - PubMed
    1. Angiolillo DJ, Fernandez‐Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, Costa MA. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49:1505–1516. DOI: 10.1016/j.jacc.2006.11.044. - DOI - PubMed

MeSH terms

Substances