Managing Hemorrhagic Complications and Bleeding Risks Associated with Platelet P2Y12 Inhibitor Therapy

Program Dates: November 16th, 2020 - November 15th, 2022
Credits: 1.0 AMA PRA Category 1 Credit™; 1.0 CNE Contact Hour and 1.0 CPE Contact Hour (0.10CEUs)

Managing Hemorrhagic Complications and Bleeding Risks Associated with Platelet P2Y12 Inhibitor Therapy

Program Overview

Antiplatelet therapy is an essential part of secondary prevention of cardiovascular events.  In particular, dual antiplatelet therapy (DAPT) — the combination of aspirin with an oral P2Y12 receptor antagonist — is the predominant approach in patients with acute coronary syndromes (ACS), coronary-artery stenting, or previous myocardial infarction (MI). The three oral P2Y12 receptor antagonists that are in use are clopidogrel, prasugrel, and ticagrelor.

An unavoidable limitation of all three oral P2Y12 receptor antagonists is increased bleeding risk from platelet inhibition, which persists for several days after drug cessation. Establishment of hemostasis can be challenging in patients with major bleeding, such as intracranial or gastrointestinal hemorrhage. In addition, urgent invasive procedures, especially emergency procedures, are associated with an increased risk of periprocedural bleeding. If an emergency procedure is indicated, the surgeon or proceduralist must proceed while accepting the increased bleeding risk, often after empirically providing platelet transfusions, despite the ineffectiveness of such transfusions in reversing the antiplatelet effects of P2Y12 inhibitors. If an urgent procedure is indicated, the proceduralist must either proceed while anticipating the increased bleeding risk or postpone the procedure for several days while accepting the risks associated with delaying a clinically indicated procedure. American College of Cardiology Foundation–American Heart Association, European Society of Cardiology, and other society guidelines recommend cessation of oral P2Y12 receptor antagonists at least 3 to 7 days before surgery.  Currently, no reversal agents for P2Y12 receptor antagonists are known. Unlike the other P2Y12 receptor antagonists, ticagrelor is a reversible inhibitor, which makes the development of a specific reversal agent for ticagrelor feasible.

In this program Drs. Pollack and Bhatt discuss the clinical need for a reversal agent for antiplatelet therapy, as well as an ongoing trial of the first such drug.  They also comment on the difficulties faced by today’s clinical researchers during the ongoing COVID-19 pandemic.

Target Audience

Interventional and clinical cardiologists, cardiothoracic and trauma surgeons, and emergency medicine/critical care specialists, as well as other clinicians, including nurses, NPs, PAs, and pharmacists who manage patients with P2Y12 inhibitor-related bleeding risks


  1. Inhibiting the Platelet P2Y12 Receptor: Efficacy and Safety
  2. Clinical Perspectives on Bleeding, Bleeding Risk, and Its Management in P2Y12 Inhibition
  3. Rationale and Methodology of a Phase 3 Placebo-Controlled Trial of a Specific Reversal Agent for a P2Y12 Inhibitor
  4. Challenges in Executing Clinical Trials in the Acute Care Environment

Learning Objectives

  1. Review the scientific basis for benefit from P2Y12 inhibition as well as the bleeding risks that result from therapy and understand the known epidemiology of clinically significant bleeding complications with these agents
  2. Analyze and understand the different perspectives of various specialists on the chronic use of P2Y12 inhibitor therapy
  3. Review current management strategies for P2Y12 inhibitor-associated bleeding risks, as well as therapies still in development
  4. Review in detail the rationale and methodology of a phase 3 clinical trial that identifies patients suitable for ticagrelor reversal and follow its execution as the science of managing patients with ticagrelor-associated hemorrhage and procedural bleeding risk


Charles V. Pollack Jr., MA, MD (Course Chair)
Department of Emergency Medicine
University of Mississippi School of Medicine
Jackson, Mississippi


Deepak L. Bhatt, MD, MPH
Executive Director of Interventional Cardiovascular Programs
Brigham and Women’s Hospital Heart & Vascular Center
Professor of Medicine, Harvard Medical School
Boston, Massachusetts


Disclosures of Conflict of Interest

It is the policy of AcademicCME that all faculty, instructors, and planners disclose real or apparent conflicts of interest relating to the topics of this educational activity.

The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CE activity:

Faculty Relationship Identified With:
Charles V. Pollack Jr., MD (Course Chair) Grant/Research Support: AstraZeneca Pharmaceuticals; PROVEPHARM INC.

Consultant/Advisor: AstraZeneca Pharmaceuticals

Deepak L. Bhatt, MD, MPH Grant/Research Support: Abbott; Afimmune Limited; Amarin Corporation; Amgen Inc.; AstraZeneca Pharmaceuticals; Bayer AG; Boehringer Ingelheim International GmbH; Bristol Myers Squibb Company; Cardax, Inc.; Chiesi USA, Inc.; CSL Behring; Eli Lilly and Company; Eisai Co., Ltd.; Ethicon Inc.; Ferring Pharmaceuticals; Forest Laboratories; Fractyl Laboratories, Inc.; Idorsia Pharmaceuticals Ltd; Ironwood Pharmaceuticals, Inc.; Ischemix; Lexicon; Medtronic; Pfizer Inc.; PhaseBio Pharmaceuticals; PLx Pharma Inc.; Regeneron Pharmaceuticals Inc.; Roche; Sanofi; Synaptic; The Medicines Company


Planners and Peer Reviewers

Timothy Hayes, MD, PhD; Kim Cheramie, MSN, RN-BC; Joseph Feick, PharmD; Gabrielle Fiorelli, CRNP and Nicole McMenamin hereby state that they or their spouse/life partner do not have any financial relationships to products or devices with any commercial interests related to the content of this activity of any amount during the past 12 months.

Accreditation Statement

In support of improving patient care, AcademicCME is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. This activity was planned by and for the healthcare team.


Credit Designation Statements

AcademicCME designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.

AcademicCME designates this enduring material for a maximum of 1.0 CNE Contact Hour, including 1.0 Pharmacotherapeutic Contact Hour (Provider number P0491).

AcademicCME designates this continuing education activity for 1.0 CPE Contact Hour (0.10 CEUs) of continuing pharmacy education credit (JA4008190-0000-20-020-H04-P).

Financial Support

This activity has been supported by an independent educational grant from PhaseBio Pharmaceuticals.

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. AcademicCME and PhaseBio Pharmaceuticals do not recommend the use of any agent outside of the labeled indications.


Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

Method of Participation

In order to claim credit, participants must complete the following:

  1. Read the learning objectives, accreditation information and faculty disclosures at the beginning of this activity.
  2. Complete the Pre-Activity Questions
  3. Read or Review the activity content.
  4. Complete the Post-Activity Test Questions and Evaluation.
  5. Learners who receive a grade of 70% or better on the Post-Activity Test Questions and complete the Evaluation will receive appropriate credit as indicated (CME, CNE, and/or CPE credit).
  • CPE credit will be posted to the learner’s CPE Monitor profile within 60 days of completion.
  • CME and CNE credit will be issued appropriate certificate of completion.
  • Others may request a “certificate of completion”.
  1. Learners should claim only the credit commensurate with the extent of their participation in the activity.

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