Author + information
- Muthiah Vaduganathan, MD, MPH,
- Arman Qamar, MD,
- Abhayjit Singh, BA,
- Ramkumar V. Venkateswaran, BS,
- Paul M. Szumita, PharmD,
- Kevin J. Croce, MD, PhD,
- Laura Mauri, MD, MSc,
- Jane A. Leopold, MD,
- Pinak B. Shah, MD,
- Piotr Sobieszczyk, MD,
- David P. Faxon, MD and
- Deepak L. Bhatt, MD, MPH∗ ()
- ↵∗Brigham and Women’s Hospital, Heart & Vascular Center, 75 Francis Street, Boston, Massachusetts 02115
Cangrelor, a rapidly acting, intravenous P2Y12 inhibitor, has been approved for use during percutaneous coronary intervention (PCI). The 3 phase 3 CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials collectively provided robust randomized data in approximately 25,000 patients supporting its utility in contemporary PCI (1). However, since approval by the U.S. Food and Drug Administration in June 2015, limited data are available exploring the uptake and outcomes associated with cangrelor in real-world clinical practice. Cangrelor was approved by our hospital formulary in September 2015 and first used in November 2015.
In this single-center retrospective cohort study, we examined practice patterns, indications for use, and clinical events in cangrelor recipients identified by in-hospital pharmacy records at a large, tertiary care institution. Two independent investigators collected and validated patient data using chart review. Efficacy and safety, as defined by the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) bleeding scale, were assessed at 48 h. The Institutional Review Board approved the study protocol.
We focus on the first 100 cangrelor recipients from initial introduction to October 2016. Major clinical characteristics were comparable with those of patients enrolled in the CHAMPION trials (2) (Table 1). In our experience, the median age was 64 years, 31% were women, 16% presented with cardiogenic shock, and 13% required mechanical circulatory support.
Overall, 94 patients underwent coronary angiography with the intent of PCI (of whom 88 received >1 stent or balloon angioplasty) for ST-segment elevation myocardial infarction (STEMI) in 49 patients, non–ST-segment elevation acute coronary syndromes (ACS) in 38, and stable angina in 7. The remaining 6 patients received cangrelor outside the immediate window of PCI (3 while awaiting coronary artery bypass graft surgery, 1 while awaiting left ventricular assist device placement, 1 perioperatively prior to semielective noncardiac surgery early after PCI for ACS, and 1 because of ileus after PCI for ACS).
In patients transitioned to P2Y12 antagonists, the majority (79.8%) received ticagrelor, while 18% received clopidogrel and 2.2% prasugrel. Oral P2Y12 inhibitor loading doses were given prior to cangrelor in 6 patients (6.7%), of whom 5 received ticagrelor and 1 prasugrel. The remaining patients (93.3%) received oral P2Y12 inhibitor loading doses during (for ticagrelor) or at the end of (for clopidogrel, prasugrel, or ticagrelor) cangrelor infusion. No patients received concomitant glycoprotein IIb/IIIa inhibitors.
The median duration of PCI was 56 min. The dose of cangrelor used in the CHAMPION trials (30 μg/kg bolus, followed by 4 μg/kg/min) was used in 90 patients, while the lower dose used in the BRIDGE (Maintenance of Platelet inihiBition With cangRelor After dIscontinuation of ThienopyriDines in Patients Undergoing surGEry) trial (0.75 μg/kg/min) was used in 6 patients for a median duration of 70.5 h (range: 18 to 115 h). The remaining 4 patients received both doses during hospitalization. Two patients who had presented with STEMI received intracoronary bolus doses of cangrelor.
At 48 h after cangrelor exposure, there were no deaths, but 4 patients died during the index hospitalization. Stent thrombosis occurred in a single patient, and there were no ischemia-driven revascularization events. All 18 bleeding events were GUSTO-defined mild to moderate, and none were classified as severe or life threatening. Four were access site related, and none represented intracranial hemorrhages. A single critically ill patient in shock experienced bleeding requiring interruption of oral antiplatelet therapy. Six of the 18 bleeds required blood transfusion. Overall, median hemoglobin was 13.5 g/dl (interquartile range: 12 to 14.8 g/dl) pre-PCI and 12.4 g/dl (interquartile range: 10.8 to 13.7 g/dl) 48 h post-PCI. Dyspnea or bradyarrhythmias requiring drug cessation were not observed.
Cangrelor is currently administered in a higher-risk cohort than represented in the CHAMPION program, most commonly in the context of PCI for STEMI. It is noteworthy that although cangrelor candidates were selected on the basis of operator discretion, there is an established institutional treatment pathway encouraging cangrelor use in patients presenting with STEMI. A minority of patients received cangrelor for bridging. Although all patients were transitioned to clopidogrel per protocol in the CHAMPION trials, 80% were transitioned to ticagrelor in our experience. Despite higher risk clinical presentations and the use of more potent oral P2Y12 inhibitors, cangrelor was generally well tolerated and associated with low rates of stent thrombosis. Although mild to moderate bleeding occurred in almost one-fifth of patients, severe, life-threatening, or intracranial bleeding was not observed.
Our experience from a tertiary care referral center may not be generalizable to overall PCI practice. Certain bleeding avoidance strategies (including low rates of concomitant glycoprotein IIb/IIIa inhibitor use  and high use of radial access) may have attenuated the risk of major bleeding with cangrelor. On the basis of this initial single-center experience, cangrelor is being used in high-risk patients undergoing PCI for ACS, is well tolerated, and is associated with low rates of clinically significant ischemic or bleeding events.
Please note: Dr. Croce is a member of the advisory board of The Medicines Company. Dr. Bhatt is a member of the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; a member of the boards of directors of the Boston VA Research Institute and the Society of Cardiovascular Patient Care; is chair of the American Heart Association Quality Oversight Committee; is a member of the data monitoring committees of the Duke Clinical Research Institute, the Harvard Clinical Research Institute, the Mayo Clinic, and the Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org), Belvoir Publications (editor-in-chief, Harvard Heart Letter), the Duke Clinical Research Institute (clinical trial steering committees), the Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor-in-chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor, associate editor), the Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (continuing medical education steering committees); is deputy editor of Clinical Cardiology, vice chair of the NCDR-ACTION Registry Steering Committee, and chair of the VA CART Research and Publications Committee; has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company (including for his role as co-chair of the CHAMPION trials); has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, PLx Pharma, and Takeda. All other authors have reported that they have no other relationships relevant to the contents of this paper to disclose. Drs. Vaduganathan and Qamar contributed equally to this work.
- 2017 American College of Cardiology Foundation