Triple Antithrombotic Therapy: Reducing Ischemic Events vs. Major Bleeding Risk

Jeannette Y. Wick, RPh, MBA, FASCP
Published Online: Monday, February 24, 2014
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When one of the newer oral anticoagulants is introduced into the treatment mix for acute coronary syndrome patients, reduction of ischemic events must be balanced against increased risk of major bleeding events.

Dual antiplatelet therapy with aspirin and aggregation inhibitors such as clopidogrel, prasugrel, or ticagrelor is becoming a cornerstone of long-term management for patients who have had an acute coronary syndrome (ACS). Members of another class of drugs—anticoagulants, both the classic warfarin and the newer agents—have also been used as secondary prevention. With the introduction of the newer oral anticoagulants (apixaban, dabigatran, and rivaroxaban), many pharmacists have questions about the transition from older to newer agents, about specific evidence-based indications, and, at times, about monitoring. A review published online on December 13, 2013, in Pharmacotherapy answers many of these questions.
 
ACS patients are at elevated risk of death even with evidence-based treatment strategies. The goal of treatment is to reduce the rate of myocardial infarction, stroke, and death from cardiovascular causes. The review authors, noting that the coagulation cascade plays a role in ACS pathophysiology, look at trials that used warfarin with dual antiplatelet therapy (DAPT) and report that these trials documented fewer ischemic events compared with DAPT alone, but also reported increased bleeding risk.
 
The review authors also note that researchers have evaluated newer oral anticoagulants—direct Factor Xa (FXa) inhibitors and direct thrombin inhibitors (DTIs)—in combination with standard post-ACS therapy. The FXa inhibitor rivaroxaban reduces the rates of ischemic events but also increases major bleeding. Another FXa inhibitor, apixaban, also increased major bleeding rates, but did not decrease the rates of ischemic events. The DTI dabigatran had a 2- to 4-fold increased risk of major bleeding, and its effect on ischemic events was unclear. Thus far, only a low-dose rivaroxaban has been proven to have a positive benefit-risk profile.
 
The authors review available anticoagulants and pipeline agents and identify studies that address long-term post-ACS management. They also summarize the European Society of Cardiology Working Group on Thrombosis’ recommendations, stressing that this group prefers newer antiplatelet agents over the addition of novel oral anticoagulants. Additionally, they list recent trials that have evaluated double versus triple antithrombotic therapy and discuss their results with an emphasis on the balance between efficacy and bleeding risk.
 
The authors conclude that more study is needed to determine whether novel oral anticoagulants will be safe and useful in post-ACS therapy. This is a comprehensive and informative review that can help pharmacists understand what we do and do not currently know about coagulation.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.
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