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Assessing Risks versus Benefits in Initiating Triple Antithrombotic Therapy

By: Jacqueline Chirico, PharmD Candidate c/o 2016

A dilemma that many clinicians face when treating patients with cardiac problems is determining the appropriateness of initiating triple antithrombotic therapy. While this is appropriate in a select patient population, it is important to understand which patients fall in this category and what risks and benefits should be considered.

Patients are placed on dual antiplatelet therapy (DAPT) when they have a coronary stent introduced or have experienced acute coronary syndrome. DAPT consists of aspirin and clopidogrel, and it can be used beyond a year in patients with a stent to prevent restenosis. Anticoagulation therapy is used in patients who are at risk of a thromboembolic event and include patients with atrial fibrillation, pulmonary embolism, deep vein thrombosis, or mechanical valves. These therapies can overlap in patients who have indications for both DAPT and oral anticoagulation therapy.1

Triple antithrombotic therapy is currently recommended for high-risk patients after acute coronary syndrome or Non-ST-Segment Myocardial Infarction (NSTEMI), who, have indications for chronic anticoagulation therapy and also have an indication for DAPT. An example of a patient who fits these criteria is someone who has had a myocardial infarction after percutaneous cardiac intervention (stent placement) or a patient who has atrial fibrillation and, also, has a stent placed.2 When this therapy is used, it is important to carefully monitor the patient and to regulate the warfarin for an INR of 2-3.2

The benefit of triple antithrombotic therapy is lower mortality and a reduction in major cardiovascular adverse events.3,4,5 A study involving 426 patients with atrial fibrillation undergoing stent placement showed a higher mortality in patients treated with DAPT alone (28%) when compared to patients on triple antithrombotic therapy (18%) (hazard ratio 3.43, 95% CI 1.61-7.54).3 A retrospective cohort study of 604 patients with atrial fibrillation who underwent percutaneous coronary interventions, all of whom, were given oral anticoagulation agents at discharge resulted in reduced major cardiovascular adverse events (hazard ration 0.4, 95% CI 0.22-0.74) and lower all-cause mortality (0.34, 95% CI 0.17-0.68).4 Lastly, a retrospective study of 478 patients with indication for oral anticoagulation therapy found that patients treated with DAPT alone had a significantly higher rate of stroke (8.8%) and stent thrombosis (5.9%) when compared with patients on triple antithrombotic therapy (2.8% and 1.9%, respectively).5 This data suggests that major cardiovascular adverse events occur more frequently when patients who have an indication for oral anticoagulation are not put on triple antithrombotic therapy, but more information would be necessary to say this for certain.6

The risk of using this approach is the heightened risk of bleeding.3 Antiplatelet and anticoagulant drugs prevent blood clots from forming and traveling to the brain or lungs. Individually, these agents each increase a patient’s risk of bleeding and, when used in combination, they further worsen this risk.3 In a retrospective study of 74 patients with coronary artery disease who were also treated with percutaneous coronary intervention, the three year incidence of major bleeding was 12.2% (9 out of 74 patients).7

Unfortunately, there is limited data on triple antithrombotic therapy, so if used, there should be clear indications, as well as the use of clinical judgment. If the benefits outweigh the risks, this therapy should be used for the smallest possible amount of time at the lowest effective doses necessary. More evidence is needed on this issue, but using the guidelines and evaluating each patient on a case-by-case basis should help health care providers have an idea of how to use this therapy in patients who need it.


  1. Triple Antithrombotic Therapy in Patients with Cardiovascular Disease. UptoDate. Available at: http://www.uptodate.com/contents/triple-antithrombotic-therapy-in-patients-with-cardiovascular-disease. Published October 22, 2013. Accessed March 5, 2015.
  2. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non–ST-Elevation Myocardial Infarction). Circulation 2007;116:e148-e304.
  3. Ruiz-Nodar JM, Marin F, Hurtado JA, et al. Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation implications for bleeding risk and prognosis. J Am Coll Cardiol. 2008;51:818-825.
  4. Ruiz-Nodar JM, Marin F, Sanchez-Paya J, et al. Efficacy and safety of drug-eluting stent use in patients with atrial fibrillation. Eur Heart J. 2009;30:932-939.
  5. Karjalainen PP, Porela P, Ylitalo A, et al. Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J. 2007;28:726-732
  6. Moser M, Olivier CB, Bode C. Triple antithrombotic therapy in cardiac patients: more questions than answers. Eur Heart J. 2014;35(4):216-23.
  7. Enomoto Y, Iijima R, Tokue M, et al. Bleeding risk with triple antithrombotic therapy in patients with atrial fibrillation and drug-eluting stents. Cardiovasc Interv Ther. 2014;29(3):193-9.

[pubmed_related keyword1=”triple” keyword2=”antithrombotic” keyword3=”therapy”]

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