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Oral Antiplatelet Therapy After Acute Coronary SyndromeA Review

Educational Objective
To review the clinical management of patients with acute coronary syndrome.
1 Credit CME
Abstract

Importance  Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States with an annual incidence of approximately 1 million. Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) reduces cardiovascular event rates after ACS.

Observations  In 2016, the updated guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) recommended aspirin plus a P2Y12 inhibitor for at least 12 months for patients with ACS. Since these recommendations were published, new randomized clinical trials have studied different regimens and durations of antiplatelet therapy. Recommendations vary according to the risk of bleeding. If bleeding risk is low, prolonged DAPT may be considered, although the optimal duration of prolonged DAPT beyond 1 year is not well established. If bleeding risk is high, shorter duration (ie, 3-6 months) of DAPT may be reasonable. A high risk of bleeding traditionally is defined as a 1-year risk of serious bleeding (either fatal or associated with a ≥3-g/dL drop in hemoglobin) of at least 4% or a risk of an intracranial hemorrhage of at least 1%. Patients at higher risk are 65 years old or older; have low body weight (BMI <18.5), diabetes, or prior bleeding; or take oral anticoagulants. The newest P2Y12 inhibitors, prasugrel and ticagrelor, are more potent, with high on-treatment residual platelet reactivity of about 3% vs 30% to 40% with clopidogrel and act within 30 minutes compared with 2 hours for clopidogrel. Clinicians should avoid prescribing prasugrel to patients with a history of stroke or transient ischemic attack because of an increased risk of cerebrovascular events (6.5% vs 1.2% with clopidogrel, P = .002) and should avoid prescribing it to patients older than 75 years or who weigh less than 60 kg. The ISAR-REACT-5 trial found that prasugrel reduced rates of death, myocardial infarction, or stroke at 1 year compared with ticagrelor among patients with ACS undergoing percutaneous coronary intervention (9.3% vs 6.9%, P = .006) with no significant difference in bleeding. Recent trials suggested that discontinuing aspirin rather than the P2Y12 inhibitor may be associated with better outcomes.

Conclusions and Relevance  Dual antiplatelet therapy reduces rates of cardiovascular events in patients with acute coronary syndrome. Specific combinations and duration of dual antiplatelet therapy should be based on patient characteristics—risk of bleeding myocardial ischemia.

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Article Information

Corresponding Author: Umair Khalid, MD, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, 2002 Holcombe Blvd (Mail Code: 111B), VAMC Office 3C-320A, Houston, TX 77030 (mukhalid@bcm.edu).

Correction: This article was corrected on June 13, 2021, to amend aspirin’s role in irreversibly inhibiting platelet activation and to change reference 19.

Accepted for Publication: January 19, 2021.

Author Contributions: Dr Khalid had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kamran, Jneid, Virani, Nambi, Khalid.

Acquisition, analysis, or interpretation of data: Kamran, Kayani, Levine.

Drafting of the manuscript: Kamran, Kayani, Khalid.

Critical revision of the manuscript for important intellectual content: Kamran, Jneid, Kayani, Virani, Levine, Nambi.

Administrative, technical, or material support: Kamran.

Supervision: Jneid, Kayani, Virani, Khalid.

Other - focus and presentation of data: Levine.

Conflict of Interest Disclosures: Dr Virani reported receiving research grants from the Department of Veterans Affairs, World Heart Federation, and the Tahir and Jooma Family and honorarium from the American College of Cardiology for serving as an associate editor for the Innovations section of the ACC.org editorial board; and serving on the steering committee of the Patient and Provider Assessment of Lipid Management (PALM). Dr Nambi reported receiving a research grant from the Department of Veterans Affairs; being a site primary investigator for studies sponsored by Merck, Amgen; receiving personal fees from Dynamed; and having a patent pending along with Roche and Baylor College of Medicine for the use of biomarkers in prediction of heart failure. No other disclosures were reported.

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