Direct Oral Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention after Acute Coronary Syndromes: a Review

  • Peter KhalilEmail author
  • Ghazal Kabbach
Ischemic Heart Disease (D Mukherjee, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Ischemic Heart Disease


Purpose of Review

As the management of acute coronary syndrome (ACS) continues to evolve, many old practices proved to be of a little benefit and other approaches established the new pillars of modern medicine. Treating ACS patients with dual antiplatelet therapy (DAPT) for a year by combining aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) has resulted in better outcomes and is currently the standard of therapy. However, owing to the persistent activation of the coagulation cascade, patients may continue to experience recurrent ischemia and high mortality rates despite compliance with the dual antiplatelet therapy. Research is underway to establish new treatment modalities for secondary prevention post-ACS, including the use of the novel direct oral anticoagulants (DOACs).

Recent Findings

Multiple trials have been conducted to evaluate the use of DOACs for the secondary prevention after ACS. Recent emerging data showed that the addition of rivaroxaban in a very low dose of 2.5 mg twice daily to the regular DAPT regimen after ACS is beneficial in the reduction of major cardiovascular events, including recurrent myocardial infarction (MI) and strokes. On the other hand, other DOACs, including apixaban, did not show similar efficacy and did not improve the cardiovascular outcomes.


Patients who experience an ACS continue to suffer long-term consequences and thromboembolic complications. Many studies have shown that after the initial ACS event, patients remain in a hypercoagulable state and are more prone to recurrent ischemic attacks including stroke, recurrent MI, or unstable angina (UA). With the objective of seeking better outcomes, it is imperative to explore more aggressive anticoagulation strategies in ACS patients. In this article, we discuss the progress that was made and the limitations we face regarding the role of different anticoagulants in this setting.


Acute coronary events Myocardial infarction Unstable angina Secondary prevention Anticoagulation Direct oral anticoagulants Antiplatelet therapy Vitamin K antagonist Factor Xa inhibitor Factor II inhibitor Direct thrombin inhibitor PAR-1 Rivaroxaban Apixaban Warfarin Vorapaxar 



Acute coronary syndrome


Adenosine diphosphate




Dual antiplatelet therapy


Direct oral anticoagulants


Extracellular matrix

F1 + 2

Prothrombin fragment 1 + 2


Food and Drug Administration


Major adverse cardiac events


Myocardial infarction


Non-ST-elevation ACS


Protease-activated receptor-1


Percutaneous coronary intervention


Stable ischemic heart disease


ST-elevation MI


Thromboxane A2


Unstable angina


Vitamin K antagonists


Von Willebrand Factor



All individuals listed as authors have contributed to the design, performance, and analysis of the review.

Compliance with Ethical Standards

Conflict of Interest

Peter Khalil and Ghazal Kabbach declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal MedicineTexas Tech University Health Sciences Center. Paul L. Foster School of MedicineEl PasoUSA

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