Author + information
- Muthiah Vaduganathan, MD, MPH,
- Arman Qamar, MD,
- Hisham A. Badreldin, PharmD, BCPS,
- David P. Faxon, MD and
- Deepak L. Bhatt, MD, MPH∗ ()
- ↵∗Brigham and Women’s Hospital Heart & Vascular Center, 75 Francis Street, Boston, Massachusetts 02115
Cardiogenic shock complicates approximately 5% of contemporary cases of acute coronary syndrome and is associated with an adverse prognosis, especially early after percutaneous coronary intervention (PCI) (1). Perturbations in hemodynamics, together with impaired gut absorption of oral antiplatelet therapies, may contribute to excess risk of early stent thrombosis (ST) in cardiogenic shock. Cangrelor, a parenteral, fast-acting, reversible P2Y12 inhibitor, may possess favorable pharmacological properties in this high-risk cohort. Although the 3 phase 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials (2) supported cangrelor’s regulatory approval for use across a spectrum of PCI, these experiences excluded patients in cardiogenic shock. As such, the relative safety and tolerability of cangrelor in these patients are presently unknown.
In this single-center experience from a large tertiary-care center, we report patterns of use and periprocedural outcomes in patients in clinical shock who received cangrelor. Shock was adjudicated by 2 investigators and defined as requiring vasopressors, inotropes, or mechanical circulatory support immediately before or during cangrelor administration. Incidence of ST at 48 h, GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries)-defined bleeding at 48 h, and post-discharge mortality were ascertained by retrospective chart review. The study protocol was approved by the Institutional Review Board.
From November 2015 to April 2017, a total of 147 patients received cangrelor, of whom 38 (26%) were in clinical shock (Table 1). Thirty-seven presented in cardiogenic shock, and 1 presented in mixed/distributive shock. Median age was 66 years and 63% were men. Patients frequently presented with cardiac arrest (42%) and/or required mechanical circulatory support (42%). Cangrelor was used in 31 patients for PCI for acute coronary syndrome, in 5 bridging to surgery (2 for coronary artery bypass graft surgery, 2 for left ventricular assist device placement, and 1 for gastrointestinal surgery), 1 because of ileus, and 1 as an antiplatelet challenge given high potential for bleeding. Twenty-nine patients received the dose of cangrelor used in the CHAMPION trials (30 μg/kg bolus, followed by 4 μg/kg/min), whereas 7 received the lower maintenance dose used in the BRIDGE (Maintenance of Platelet Inhibition With Cangrelor After Discontinuation of Thienopyridines in Patients Undergoing Surgery) trial (0.75 μg/kg/min) (3), and 2 received both doses. The median duration of BRIDGE dosing was 34 h (range 13 to 233 h). Most patients transitioned to an oral P2Y12 antagonist after PCI (n = 30) were treated with ticagrelor (80%). Oral loading doses were administered before PCI in 3 patients (1 prasugrel, 2 ticagrelor), during PCI in 5 patients (all ticagrelor), and after PCI in the remaining 22 patients (5 clopidogrel, 17 ticagrelor). No patients received concomitant glycoprotein IIb/IIIa inhibitors.
During the first 48 h, there was no ST in the 38 patients in clinical shock and 1 ST in the 109 hemodynamically stable patients. In the shock subset, all 11 GUSTO-defined bleeding events (29%) were classified as mild or moderate. Five required ≥1 blood transfusion. Two were access site–related, 2 were gastrointestinal, 2 were genitourinary, 4 were from multiple sites, 1 was presumed with an unidentified source, and none were intracranial. Two critically ill patients required temporary disruption in cangrelor because of excess bleeding. In the hemodynamically stable subset, there were 16 GUSTO-defined mild or moderate bleeding events (15%) of which 6 were access site–related, 4 gastrointestinal, 1 retroperitoneal, 1 genitourinary, and 4 were from other or unidentified sources. There was no intracranial bleeding. Four required ≥1 blood transfusion. In both subsets, adverse effects of cangrelor infusion (dyspnea or bradyarrhythmias) were not observed. There were 5 deaths and 1 terminally ill patient in each of the clinical shock and hemodynamically stable cohorts at median 12-months post-discharge follow-up.
We present the largest real-world experience of cangrelor use in cardiogenic shock, a cohort excluded from the CHAMPION trial program. In this single-center series (4), more than one-quarter of patients receiving cangrelor were in clinical shock. Mild/moderate bleeding and short-term mortality occurred at approximately twice the rate observed in hemodynamically stable patients. Despite their high-risk presentations, there was no observed ST or severe/life-threatening bleeding at 48 h, and no patients required bailout glycoprotein IIb/IIIa inhibitors.
Our clinical series is limited to a single-center experience with a small sample size. Critically ill patients in cardiogenic shock at risk for gut malabsorption are well-suited for rapidly acting and reversible intravenous antiplatelet therapies, but are at high risk of attendant bleeding complications. Augmenting use of radial access, considering bivalirudin instead of heparin, and avoiding concurrent administration of glycoprotein IIb/IIIa inhibitors (5) may further improve the bleeding profile of cangrelor. The optimization of ischemic and bleeding risks in patients in cardiogenic shock represents an unmet clinical need. Our initial data suggest that cangrelor may offer a potent, parenteral strategy in patients in cardiogenic shock and seems to be well-tolerated with low rates of clinically significant ischemic or bleeding events.
Please note: Drs. Vaduganathan and Qamar are supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (T32HL007604). Dr. Deepak L. Bhatt is on the Advisory Board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; the Board of Directors of Boston VA Research Institute and the Society of Cardiovascular Patient Care; the Chair of the American Heart Association Quality Oversight Committee; the Data Monitoring Committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; 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), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); is Deputy Editor of Clinical Cardiology, Chair of NCDR-ACTION Registry Steering Committee, and Chair of VA CART Research and Publications Committee; received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi (including for his role as Co-Chair of the CHAMPION trials), Eisai, Ethicon, Forest Laboratories, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company (including for his role as Co-Chair of the CHAMPION trials); received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is Site Co-Investigator for Biotronik, Boston Scientific, and St. Jude Medical; is a Trustee of the American College of Cardiology; and received unfunded research from FlowCo, PLx Pharma, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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