Utility of Antithrombotic Therapy in Chronic Systolic Heart Failure

Case

JD is a 67-year-old woman seen in the family medicine clinic for an annual physical exam. Past medical history is significant for hypertension, dyslipidemia, and chronic non-ischemic systolic heart failure. Her ejection fraction is 35%, lipid levels are at goal per NCEP A TP III guidelines, and blood pressures over the past year have consistently been less than 120/80 mm Hg. Home medications include metoprolol succinate 200 mg daily, lisinopril 20 mg daily, spironolactone 25 mg daily, and atorvastatin 40 mg daily. JD’s primary care physician seeks your opinion on whether or not to initiate an antithrombotic agent (oral anticoagulation and/or antiplatelet agents) for primary prevention of major adverse cardiovascular events (MACEs).

Answer

Heart failure with reduced ejection fraction is associated with significant morbidity and mortality, with approximately 30% of patients experiencing venous thromboembolism, cardioembolic stroke, and sudden death.¹ The substantial rate of thrombotic complications has been attributed to blood flow abnormalities (eg, low cardiac output, depressed contractility), vessel wall abnormalities (eg, endothelial dysfunction), and abnormal blood constituents (eg, coagulation and platelet abnormalities, neuroendocrine system activation).

Four randomized controlled trials have explored this clinical question.^2-5 All of these studies were stopped early due to slow recruitment; therefore, results should be interpreted with caution. In all 4 studies, no significant difference was observed between any of the studied treatment groups on the incidence of MACE (examples include but are not limited to all-cause death, non-fatal myocardial infarction, non-fatal-stroke, pulmonary embolism, rehospitalization, heart failure exacerbation) when reported as the primary composite outcome. However, increased risk of heart failure hospitalization, a secondary end point, was identified in patients receiving aspirin compared with warfarin and placebo in the Warfarin/Aspirin Study in Heart Failure (WASH) trial and in patients receiving aspirin compared with warfarin in the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) study.^2,4 In contrast, a nonsignificant increase in heart failure hospitalization was observed with warfarin compared with aspirin in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial.⁵ Furthermore, a higher incidence of ischemic stroke was observed with aspirin compared to warfarin in WATCH and WARCEF.^4,5 Higher risk of bleeding, including major hemorrhage, was demonstrated in all 4 trials with warfarin.^2-5

Consensus statements conclude anti-platelet therapy should not be initiated unless a specific indication exists (eg, coronary artery disease).^1,6-8 Similarly, data do not support the use of warfarin in all systolic heart failure patients who are in sinus rhythm given no overall benefit was observed in reducing mortality and other MACEs, although warfarin may contribute to reducing ischemic stroke. However, a conversation between the health care provider and patient is encouraged regarding the pros (ie, potential benefit in reducing stroke) and cons (ie, increased risk of bleeding) of anticoagulation in this setting.

Based on existing literature, guidelines, and consensus statements, antithrombotic therapy is currently not warranted in JD as she does not have compelling indications for these agents.

Ilya M. Danelich, PharmD, BCPS, is a clinical pharmacist at the Mayo Clinic in Rochester, Minnesota. Jennifer M. Lose, PharmD, BCPS, is a clinical pharmacist at the Mayo Clinic in Rochester, Minnesota.

References:

• Lip GY, Ponikowski P, Andreotti F, et al. Thrombo-embolism and antithrombotic therapy for heart failure in sinus rhythm: a joint consensus document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis. Eur J Heart Fail. 2012;14:681-695.
• Cleland JG, Findlay I, Jafri S, et al. The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure. Am Heart J. 2004;148:157-164.
• Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK; HELAS investigators. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Eur J Heart Fail. 2006;8:428-432.
• Massie BM, Collins JF, Ammon SE, et al. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation. 2009;119:1616-1624.
• Homma S, Thompson JL, Pullicino PM, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366:1859-1869.
• Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: a Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [published online June 5, 2013]. Circulation.
• McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology: developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787-1847.
• Heart Failure Society of America; Lindenfeld J, Albert NM, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010;16:e1-e194.