You Make the Call: Is warfarin recommended for a patient with recurrent coronary artery closure?

Michael Kroll, MD
Professor of Medicine, Chief of the Section of Benign Hematology, The University of Texas MD Anderson Cancer Center

This month, Michael Kroll, MD, discusses management of a patient with recurrent coronary artery closure.

And don’t forget to check out next month’s clinical dilemma – send in your responses for a chance to win an ASH Clinical News-themed prize!


I am an oncologist requesting advice about a 71-year-old man with recurrent coronary artery closure. He had a stent placed in April 2019, which occluded, and he underwent coronary artery bypass grafting (CABG) 4 months later. In April 2020, a grafted vessel occluded. Since April 2019 he has received clopidogrel, ticagrelor, and prasugrel at different times. Now he is on aspirin only. His cardiologist did a hypercoagulability work-up and found a mildly decreased protein S activity level of 57%. I repeated the test a few days later and found that his protein S activity level was 70%. I am planning to repeat the test in 4 weeks. The patient is due to undergo repeat CABG soon. Is there any role for warfarin?


Arterial thrombosis is triggered by platelet activation. Antiplatelet therapy is effective for primary prevention of myocardial infarction (MI) in higher-risk patients and for secondary prevention of MI in all patients suffering a coronary ischemic event.1,2 In contrast, anticoagulation therapy to prevent fibrin deposition is ineffective for primary prevention and is only moderately effective for secondary prevention of MI. In fact, warfarin is rarely used for secondary prevention because its few benefits are counterbalanced by an increased risk of major bleeding.3 So, there is no role for warfarin here.

Since the 2017 report of the results of the COMPASS trial (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS), there has been enthusiasm about combining a single antiplatelet agent with a low dose of the direct factor Xa inhibitor rivaroxaban in patients after acute coronary syndrome or MI (with or without a percutaneous coronary intervention or coronary bypass grafting).4 FDA approval of this program (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg per day) for secondary prevention of major cardiovascular events (i.e., cardiovascular death, MI, and stroke) in patients with chronic coronary artery disease or peripheral artery disease has prompted questions similar to this clinical dilemma, such as: When should one use this type of dual antithrombotic therapy, either as an alternative to starting dual antiplatelet therapy or as a new approach for patients already taking dual antiplatelet therapy?

In this less stable patient with significant problems from coronary artery thrombosis despite percutaneous coronary intervention (PCI) and CABG, I do not recommend a dual antithrombotic approach. Rather, based on the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in MI 54), I recommend dual antiplatelet therapy with ticagrelor 180 mg loading dose followed by 90 mg orally twice per day, plus aspirin 81 mg daily.5 Please note that more than 80% of the 21,000+ patients enrolled in the PEGASUS-TIMI trial had received a PCI. If dual antiplatelet treatment had clearly failed the patient in the past or were to fail in the future, you can retreat to the COMPASS program of rivaroxaban 2.5 mg orally twice per day plus aspirin 81 mg daily. Otherwise, I would substitute ticagrelor for aspirin and continue low-dose rivaroxaban.

I do not consider protein S deficiency to be a risk factor for coronary artery disease and its measurement is often misleading, so I would not factor this into your management plan.6,7,8

Please consider that the vascular component of Virchow’s triad appears to be the main pathophysiological factor in coronary artery disease, so antiplatelet or anticoagulant therapies, no matter how intensive, may prove inadequate until the patient has revascularization.


  1. U.S. Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. Accessed July 19, 2020, from https://uspreventive
  2. American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol. 2016;68:1082-1115.
  3. Turgeon RD, Ackman ML, Babadagli HE, et al. The role of direct oral anticoagulants in patients with coronary artery disease. J Cardiovasc Pharmacol Ther. 2019;24:103-112.
  4. Eikelboom JW, Connolly SJ, Bosch J et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319-30.
  5. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-800.
  6. Voetsch B, Loscalzo J. Genetic determinants of arterial thrombosis. Arterioscler Thromb Vasc Biol. 2004;24:216-229.
  7. Ginsburg D. Genetic risk factors for arterial thrombosis and inflammation. Hematology Am Soc Hematol Educ Program. 2005;442-444.
  8. Marlar RA, Gausman JN. Protein S abnormalities: a diagnostic nightmare. Am J Hematol. 2011;86:418-421.

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I am caring for a young patient with hereditary hemochromatosis who is 36 weeks pregnant and has a ferritin level of 15 mcg/L. Despite the genetic diagnosis, I am tempted to order intravenous iron because of concerns about effects of iron deficiency on the fetus. How would you recommend I proceed?

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