Antithrombotic therapy in patients with heart failure
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
- Gregory YH Lip, MD, FRCPE, FESC, FACC
Gregory YH Lip, MD, FRCPE, FESC, FACC
- Professor of Cardiovascular Medicine
- The University of Birmingham, UK
Studies in patients with heart failure (HF), left ventricular systolic dysfunction, or both have noted high rates of thromboembolic events as compared to the general population. While more evidence is available on thromboembolic risk in patients with left ventricular systolic dysfunction (with or without HF), evidence suggests that HF with preserved ejection fraction is also be associated with excess thromboembolism and stroke risk. (See 'Epidemiology' below.)
Thrombus in the left heart chambers can lead to embolic stroke and other systemic embolic events, while pulmonary emboli and paradoxical emboli originate from either deep venous thrombus or thrombus in the right heart chambers. Low cardiac output, decreased physical activity, and peripheral edema all predispose to venous thrombi.
This topic will discuss the risk of thromboembolism and indications for anticoagulation in patients with HF.
Antithrombotic therapy in clinical settings that may be associated with HF is discussed separately:
- 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.
- Dries DL, Rosenberg YD, Waclawiw MA, Domanski MJ. Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: evidence for gender differences in the studies of left ventricular dysfunction trials. J Am Coll Cardiol 1997; 29:1074.
- Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336:251.
- Dunkman WB, Johnson GR, Carson PE, et al. Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 1993; 87:VI94.
- Freudenberger RS, Hellkamp AS, Halperin JL, et al. Risk of thromboembolism in heart failure: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Circulation 2007; 115:2637.
- Witt BJ, Gami AS, Ballman KV, et al. The incidence of ischemic stroke in chronic heart failure: a meta-analysis. J Card Fail 2007; 13:489.
- Abdul-Rahim AH, Perez AC, Fulton RL, et al. Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials. Circulation 2015; 131:1486.
- Sandhu RK, Hohnloser SH, Pfeffer MA, et al. Relationship between degree of left ventricular dysfunction, symptom status, and risk of embolic events in patients with atrial fibrillation and heart failure. Stroke 2015; 46:667.
- Solomon SD, Anavekar N, Skali H, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation 2005; 112:3738.
- Zile MR, Gaasch WH, Anand IS, et al. Mode of death in patients with heart failure and a preserved ejection fraction: results from the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-Preserve) trial. Circulation 2010; 121:1393.
- Kannel WB, Wolf PA, Verter J. Manifestations of coronary disease predisposing to stroke. The Framingham study. JAMA 1983; 250:2942.
- Witt BJ, Brown RD Jr, Jacobsen SJ, et al. Ischemic stroke after heart failure: a community-based study. Am Heart J 2006; 152:102.
- Alberts VP, Bos MJ, Koudstaal P, et al. Heart failure and the risk of stroke: the Rotterdam Study. Eur J Epidemiol 2010; 25:807.
- Lip GY, Rasmussen LH, Skjøth F, et al. Stroke and mortality in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study. BMJ Open 2012; 2.
- Lip GY, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow's triad revisited. J Am Coll Cardiol 1999; 33:1424.
- Jafri SM, Ozawa T, Mammen E, et al. Platelet function, thrombin and fibrinolytic activity in patients with heart failure. Eur Heart J 1993; 14:205.
- Gibbs CR, Blann AD, Watson RD, Lip GY. Abnormalities of hemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm: effects of angiotensin-converting enzyme inhibitor and beta-blocker therapy. Circulation 2001; 103:1746.
- Cugno M, Mari D, Meroni PL, et al. Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation. Br J Haematol 2004; 126:85.
- Jafri SM, Mammen EF, Masura J, Goldstein S. Effects of warfarin on markers of hypercoagulability in patients with heart failure. Am Heart J 1997; 134:27.
- Lam CS, Brutsaert DL. Endothelial dysfunction: a pathophysiologic factor in heart failure with preserved ejection fraction. J Am Coll Cardiol 2012; 60:1787.
- Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22:983.
- Cioffi G, Pozzoli M, Forni G, et al. Systemic thromboembolism in chronic heart failure. A prospective study in 406 patients. Eur Heart J 1996; 17:1381.
- McMurray JJ, Ezekowitz JA, Lewis BS, et al. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail 2013; 6:451.
- Cokkinos DV, Haralabopoulos GC, Kostis JB, et al. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Eur J Heart Fail 2006; 8:428.
- Falk RH, Foster E, Coats MH. Ventricular thrombi and thromboembolism in dilated cardiomyopathy: a prospective follow-up study. Am Heart J 1992; 123:136.
- Stratton JR, Resnick AD. Increased embolic risk in patients with left ventricular thrombi. Circulation 1987; 75:1004.
- Ciaccheri M, Castelli G, Cecchi F, et al. Lack of correlation between intracavitary thrombosis detected by cross sectional echocardiography and systemic emboli in patients with dilated cardiomyopathy. Br Heart J 1989; 62:26.
- Gottdiener JS, Gay JA, VanVoorhees L, et al. Frequency and embolic potential of left ventricular thrombus in dilated cardiomyopathy: assessment by 2-dimensional echocardiography. Am J Cardiol 1983; 52:1281.
- Weinsaft JW, Kim HW, Crowley AL, et al. LV thrombus detection by routine echocardiography: insights into performance characteristics using delayed enhancement CMR. JACC Cardiovasc Imaging 2011; 4:702.
- Kalaria VG, Passannante MR, Shah T, et al. Effect of mitral regurgitation on left ventricular thrombus formation in dilated cardiomyopathy. Am Heart J 1998; 135:215.
- Mahajan N, Ganguly J, Simegn M, et al. Predictors of stroke in patients with severe systolic dysfunction in sinus rhythm: role of echocardiography. Int J Cardiol 2010; 145:87.
- Melgaard L, Gorst-Rasmussen A, Lane DA, et al. Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation. JAMA 2015; 314:1030.
- 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.
- Lip GY, Shantsila E. Anticoagulation versus placebo for heart failure in sinus rhythm. Cochrane Database Syst Rev 2014; :CD003336.
- Fuster V, Gersh BJ, Giuliani ER, et al. The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol 1981; 47:525.
- Kyrle PA, Korninger C, Gössinger H, et al. Prevention of arterial and pulmonary embolism by oral anticoagulants in patients with dilated cardiomyopathy. Thromb Haemost 1985; 54:521.
- 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.
- 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.
- Lee M, Saver JL, Hong KS, et al. Risk-benefit profile of warfarin versus aspirin in patients with heart failure and sinus rhythm: a meta-analysis. Circ Heart Fail 2013; 6:287.
- Hopper I, Skiba M, Krum H. Updated meta-analysis on antithrombotic therapy in patients with heart failure and sinus rhythm. Eur J Heart Fail 2013; 15:69.
- Shantsila E, Lip GY. Antiplatelet versus anticoagulation treatment for patients with heart failure in sinus rhythm. Cochrane Database Syst Rev 2016; 9:CD003333.
- Levine MN, Raskob G, Hirsh J. Hemorrhagic complications of long-term anticoagulant therapy. Chest 1989; 95:26S.
- Landefeld CS, Cook EF, Flatley M, et al. Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy. Am J Med 1987; 82:703.
- Husted S, Andreasen F. Problems encountered in long-term treatment with anticoagulants. Acta Med Scand 1976; 200:379.
- Visser LE, Bleumink GS, Trienekens PH, et al. The risk of overanticoagulation in patients with heart failure on coumarin anticoagulants. Br J Haematol 2004; 127:85.
- Bermingham M, Shanahan MK, O'Connell E, et al. Aspirin use in heart failure: is low-dose therapy associated with mortality and morbidity benefits in a large community population? Circ Heart Fail 2014; 7:243.
- Cleland JG, Parsons S. Aspirin for heart failure: theory- or evidence-based? Circ Heart Fail 2014; 7:237.
- Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e637S.
- WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, 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. Circulation 2013; 128:e240.
- Heart Failure Society of America, Lindenfeld J, Albert NM, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010; 16:e1.
- 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.
- Incidence of thromboembolism or stroke in heart failure populations
- Heart failure as stroke risk factor
- PATHOGENESIS OF THROMBOEMBOLISM IN HEART FAILURE
- RISK FACTORS FOR THROMBOEMBOLISM
- Atrial fibrillation
- Left ventricular systolic dysfunction
- Left ventricular thrombus
- Clinical risk models
- ROLE OF ANTITHROMBOTIC THERAPY
- Our approach
- Evidence on antithrombotic therapy in HF
- - Antithrombotic therapy compared to placebo
- - Comparison of aspirin to warfarin
- - Risks of anticoagulation
- - Effect of aspirin on HF outcomes
- Recommendations of others
- SUMMARY AND RECOMMENDATIONS