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Role of Antithrombotic Agents in Heart Failure

  • Congestive Heart Failure (J Lindenfeld, Section Editor)
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Abstract

Despite a vast body of research on antithrombotic therapy for patients with cardiac disease, there are few clinical settings where robust evidence of their benefit exists. Patients with heart failure often have vascular disease and atrial fibrillation contributing to their poor prognosis. For patients with heart failure and atrial fibrillation, anticoagulants are appropriate. For patients with heart failure in sinus rhythm, the weight of evidence suggests that doctors should generally avoid using any antithrombotic agent even if the patient has coronary artery disease. If there is a compulsion to treat, then there is less evidence of harm with clopidogrel or warfarin than with aspirin, although most receive aspirin. More research is required for this “evidence-light” problem. For those with the opportunity, engaging with a randomized trial is clinically and scientifically appropriate. The dilemma for such studies is the comparator. Should it be against or in addition to “standard of care” or both?

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References

  1. Cleland JGF. Is aspirin ‘The Weakest Link’ in cardiovascular prophylaxis. The surprising lack of evidence supporting the use of aspirin for cardiovascular disease. Prog Cardiovasc Dis. 2002;44:275–92.

    Article  PubMed  CAS  Google Scholar 

  2. Khand A, Rankin AC, Kaye GC, Cleland JGF. Systematic review of the management of atrial fibrillation in patients with heart failure. Eur Heart J. 2000;21:614–32.

    Article  PubMed  CAS  Google Scholar 

  3. Khand A, Cleland JGF, Deedwania P. Prevention of and medical therapy for atrial arrhythmias in heart failure. Heart Fail Rev. 2002;7:267–83.

    Article  PubMed  CAS  Google Scholar 

  4. Cleland JG. Time for a proper study of aspirin after a vascular event? BMJ. 2008;337:a2583.

    Article  PubMed  Google Scholar 

  5. Lip GYH, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow’s triad revisited. J An Coll Cardiol. 1999;33:1424–6.

    Article  CAS  Google Scholar 

  6. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke. The Framingham Study. Stroke. 1991;22:983–9.

    Article  PubMed  CAS  Google Scholar 

  7. Good JM, Nihoyannopoulos P, Ghatei MA, et al. Elevated plasma endothelin concentrations in heart failure; an effect of angiotensin II? Eur Heart J. 1994;15(12):1634–40.

    PubMed  CAS  Google Scholar 

  8. Jhund PS, Davie AP, McMurray JJ. Aspirin inhibits the acute venodilator response to furosemide in patients with chronic heart failure. JACC. 2001;37:1234–8.

    PubMed  CAS  Google Scholar 

  9. Davie AP, Love MP, McMurray JJV. Even low-dose aspirin inhibits arachidonic acid-induced vasodilation in heart failure. Clin Pharmacol Ther. 2000;67(5):530–7.

    Article  PubMed  CAS  Google Scholar 

  10. Habib F, Dutka D, Crossman D, Oakley CM, Cleland JGF. Enhanced basal nitric oxide production in heart failure: another failed counter regulatory vasodilator mechanism? Lancet. 1994;344(8919):371–3.

    Article  PubMed  CAS  Google Scholar 

  11. Haynes G, Webb DJ. Endothelium-dependent modulation of responses to endothelin-1 in human veins. Clin Sci. 1993;84:427–33.

    PubMed  CAS  Google Scholar 

  12. de Silva R, Nikitin NP, Witte KK, et al. Effects of applying a standardised management algorithm for moderate to severe renal dysfunction in patients with chronic stable heart failure. Eur J Heart Fail. 2007;9:415–23.

    Article  PubMed  Google Scholar 

  13. Ranke C, Hecker H, Creutzig A, Alexander K. Dose-dependent effect of aspirin on carotid atherosclerosis. Circulation. 1993;87(6):1873–9.

    PubMed  CAS  Google Scholar 

  14. Knottenbelt C, Brennan PJ, Meade TW. For the MRC general practice research framework. Antithrombotic treatment and the incidence of angina pectoris. Arch Intern Med. 2002;162:881–6.

    Article  PubMed  CAS  Google Scholar 

  15. Pulmonary Embolism Prevention (PEP) Trial Collaborative Group. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000;355(9212):1295–302.

    Article  Google Scholar 

  16. van Dantzig JM, Becker AE. Sudden cardiac death and acute pathology of coronary arteries. Eur Heart J. 1986;7(11):987–91.

    PubMed  Google Scholar 

  17. Burke AP, Kolodgie FD, Farb A, et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation. 2001;103(7):934–40.

    PubMed  CAS  Google Scholar 

  18. Sbarouni E, Bradshaw A, Andreotti F, Tuddenham E, Oakley CM, Cleland JGF. Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. Am Heart J. 1994;127:607–12.

    Article  PubMed  CAS  Google Scholar 

  19. Loh PH, Tin L, Goode K, Windram J, Reddy P. Disturbed haemostasis predicts mortality in patients with heart failure due to left ventricular systolic dysfunction. Eur Heart J. 2007;28(Abstr Suppl):810.

    Google Scholar 

  20. 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;103:1746–51.

    PubMed  CAS  Google Scholar 

  21. Kannel WB, Abbott RD. Incidence and prognosis of unrecognised myocardial infarction: an update on the Framingham Study. N Engl J Med. 1984;311:1144–7.

    Article  PubMed  CAS  Google Scholar 

  22. Perna ER, Macin SM, Parras JI, et al. Cardiac troponin T levels are associated with poor short-and long-term prognosis in patients with acute cardiogenic pulmonary oedema. Am Heart J. 2002;143:814–20.

    Article  PubMed  CAS  Google Scholar 

  23. Uretsky B, Thygesen K, Armstrong PW, et al. Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival study (ATLAS) trial. Circulation. 2000;102:611–6.

    PubMed  CAS  Google Scholar 

  24. Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–89.

    Article  PubMed  CAS  Google Scholar 

  25. Hansson L, Zanchetti A, Carruthers SG, et al. Effect of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet. 1998;351:1755–62.

    Article  PubMed  CAS  Google Scholar 

  26. Cleland JGF, Massie BM, Packer M. Sudden death in heart failure: vascular or electrical? Eur J Heart Fail. 1999;1:41–5.

    Article  PubMed  CAS  Google Scholar 

  27. Cleland JGF, Thygesen K, Uretsky BF, et al. Cardiovascular critical event pathways for the progression of heart failure. A report from the ATLAS study. Eur Heart J. 2001;22:1601–12.

    Article  PubMed  CAS  Google Scholar 

  28. Schmidt R, Fazekas F, Offenbacher H, Dusleag J, Lechner H. Brain magnetic resonance imaging and neuropsychological evaluation of patients with idiopathic dilated cardiomyopathy. Stroke. 1991;22:195–9.

    Article  PubMed  CAS  Google Scholar 

  29. Cleland JGF. anticoagulant and antiplatelet therapy in heart failure. Curr Opin Cardiol. 1997;12:276–87.

    Article  PubMed  CAS  Google Scholar 

  30. Cleland JGF, Thackray S. Antiplatelet therapy for ACS: a house in need of a spring clean. Prescriber. 2009;20(23/24):7–10.

    Article  Google Scholar 

  31. Loh E, Sutton MS, Wun C-CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med. 1997;336:251–7.

    Article  PubMed  CAS  Google Scholar 

  32. Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfranctionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996;334:677–81.

    Article  PubMed  CAS  Google Scholar 

  33. Darze ES, Latado AL, Guimaraes AG, et al. Incidence and clinical predictors of pulmonary embolism in severe heart failure patients admitted to a coronary care unit. Chest. 2005;128(4):2576–80.

    Article  PubMed  Google Scholar 

  34. Darze ES, Latado AL, Guimaraes AG, et al. Acute pulmonary embolism is an independent predictor of adverse events in severe decompensated heart failure patients. Chest. 2007;131(6):1838–43.

    Article  PubMed  Google Scholar 

  35. Orn S, Cleland JG, Romo M, Kjekshus J, Dickstein K. Recurrent infarction causes the most deaths following myocardial infarction with left ventricular dysfunction. Am J Med. 2005;118(7):752–8.

    Article  PubMed  Google Scholar 

  36. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008;29(19):2388–442.

    Article  PubMed  CAS  Google Scholar 

  37. Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977–2016.

    Article  PubMed  Google Scholar 

  38. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2005;112:154–235.

    Article  Google Scholar 

  39. Cleland JGF, Oakley CM. Vascular tone in heart failure: the neuroendocrine-therapeutic interface. Br Heart J. 1991;66:264–7.

    Article  PubMed  CAS  Google Scholar 

  40. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357(22):2248–61.

    Article  PubMed  CAS  Google Scholar 

  41. MacIntyre IM, Jhund PS, McMurray JJ. Aspirin inhibits the acute arterial and venous vasodilator response to captopril in patients with chronic heart failure. Cardiovasc Drugs Ther. 2005;19(4):261–5.

    Article  CAS  Google Scholar 

  42. Davie AP, Love MP, McMurray JJV. Even low-dose aspirin inhibits arachidonic acid-induced vasodilatation in heart failure. Clin Pharm Ther. 2000;67:530–7.

    Article  CAS  Google Scholar 

  43. Meune C, Mahe I, Mourad JJ, et al. Aspirin alters arterial function in patients with chronic heart failure treated with ACE inhibitors: a dose-mediated deleterious effect. Eur J Heart Fail. 2003;5(3):271–9.

    Article  PubMed  CAS  Google Scholar 

  44. Hall D, Zeitler H, Rudolph W. Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure. J Am Coll Cardiol. 1992;20:1549–55.

    Article  PubMed  CAS  Google Scholar 

  45. Al-Khadra AS, Salem DN, Rand WM, Udelson JE, Smith JJ, Konstam MA. Antiplatelet agents and survival: a cohort analysis from the studies of left ventricular dysfunction (SOLVD) trial. J Am Coll Cardiol. 1998;31:419–25.

    Article  PubMed  CAS  Google Scholar 

  46. Weil J, Colin-Jones D, Langman M, et al. Prophylactic use of aspirin and risk of peptic ulcer bleeding. Br Med J. 1995;310:827–30.

    Article  CAS  Google Scholar 

  47. Kelly MJ, Kaugman DW, Jurgelon JM, Sheehan J, Koff RS, Shapiro S. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product. Lancet. 1996;348(9039):1413–6.

    Article  PubMed  CAS  Google Scholar 

  48. Weil J, Langman MJS, Wainwright P, et al. Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs. Gut. 2000;46:27–31.

    Article  PubMed  CAS  Google Scholar 

  49. de Silva R, Rigby AS, Witte KKA, et al. Anemia, renal dysfunction and their interaction in patients with chronic heart failure. Am J Cardiol. 2006;98(3):391–8.

    Article  PubMed  Google Scholar 

  50. Teo K, Yusuf S, Pfeffer M, et al. Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review. Lancet. 2002;360(9339):1037–43.

    Article  PubMed  CAS  Google Scholar 

  51. Cleland JG, Torabi A, Zhang J, Chelliah RK. Anti-thrombotic Agents. In: McDonagh TA, Gardner RS, Clark AL, Dargie HJ (eds) Oxford textbook of heart failure. Oxford; 2011;pp. 437–46.

  52. Dagenais GR, Pogue J, Fox K, Simoons ML, Yusuf S. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet. 2006;368(9535):581–8.

    Article  PubMed  CAS  Google Scholar 

  53. Lindenfeld J, Robertson AD, Lowes BD, Bristow MR. For the MOCHA Investigators. Aspirin impairs reverse myocardial remodeling in patients with heart failure treated with beta-blockers. J Am Coll Cardiol. 2001;38(7):1950–6.

    Article  PubMed  CAS  Google Scholar 

  54. Cleland JGF, Pennell DJ, Ray SG, et al. Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial. Lancet. 2003;362:14–21.

    Article  PubMed  CAS  Google Scholar 

  55. Storey RF, Becker RC, Harrington RA, et al. Characterization of dyspnoea in PLATO study patients treated with ticagrelor or clopidogrel and its association with clinical outcomes. Eur Heart J. 2011;32(23):2945–53.

    Article  PubMed  CAS  Google Scholar 

  56. Sanada S, Asanuma H, Koretsune Y, et al. Long-term oral administration of dipyridamole improves both cardiac and physical status in patients with mild to moderate chronic heart failure: a prospective open-randomized study. Hypertens Res. 2007;30(10):913–9.

    Article  PubMed  CAS  Google Scholar 

  57. Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008;359(12):1238–51.

    Article  PubMed  CAS  Google Scholar 

  58. Meune C, Wahbi K, Fulla Y, et al. Effects of aspirin and clopidogrel on plasma brain natriuretic peptide in patients with heart failure receiving ACE inhibitors. Eur J Heart Fail. 2007;9(2):197–201.

    Article  PubMed  CAS  Google Scholar 

  59. Jug B, Sebestjen M, Sabovic M, Keber I. Clopidogrel is associated with a lesser increase in NT-proBNP when compared to aspirin in patients with ischemic heart failure. J Card Fail. 2006;12(6):446–51.

    Article  PubMed  CAS  Google Scholar 

  60. Meune C, Mahe I, Cohen-Solal A. Comparative effect of aspirin and clopidogrel on arterial function in CHF. Int J Cardiol. 2006;106(1):61–6.

    Article  PubMed  Google Scholar 

  61. Guazzi M, Pontone G, Agostoni P. Aspirin worsens exercise performance and pulmonary gas exchange in patients with heart failure who are taking angiotensin-converting enzyme inhibitors. Am Heart J. 1999;138:254–60.

    Article  PubMed  CAS  Google Scholar 

  62. Guazzi M, Marenzi G, Alimento M, Contini M, Agostoni P. Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin. Circulation. 1997;95:1930–6.

    PubMed  CAS  Google Scholar 

  63. Kindsvater S, Leclerc K, Ward J. Effects of coadministration of aspirin or clopidogrel on exercise testing in patients with heart failure receiving angiotensin-converting enzyme inhibitors. Am J Cardiol. 2003;91(11):1350–2.

    Article  PubMed  CAS  Google Scholar 

  64. Bhatt DL, Chew DP, Hirsch AT, Ringleb PB, Hacke W, Topol EJ. Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation. 2001;103:363–8.

    PubMed  CAS  Google Scholar 

  65. Cleland JGF, Cohen-Solal A, Cosin-Aguilar J, et al. An International Survey of the Management of Heart Failure in Primary Care. The IMPROVEMENT of Heart Failure Programme. Lancet. 2002;360:1631–9.

    Article  PubMed  CAS  Google Scholar 

  66. Cleland JGF, Swedberg K, Follath F, et al. The EuroHeart Failure Survey Programme: survey on the quality of care among patients with heart failure in Europe. Part 1: Patient Characteristics and Diagnosis. Eur Heart J. 2003;24:422–63.

    Google Scholar 

  67. Al-Khadra AS, Salem DN, Rand WM, Udelson JE, Smith JJ, Konstam MA. Warfarin anticoagulation and survival: a cohort analysis from the studies of left ventricular dysfunction. JACC. 1998;31:749–53.

    PubMed  CAS  Google Scholar 

  68. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.

    Article  PubMed  CAS  Google Scholar 

  69. Cleland JGF, Shelton R, Nikitin NP, Ford S, Frison L, Grind M. Prevalence of markers of heart failure in patients with atrial fibrillation and the effects of ximelagatran compared to warfarin on the incidence of morbid and fatal events: a report from the SPORTIF III and V trials. Eur J Heart Fail. 2007;9(6–7):730–9.

    Article  PubMed  CAS  Google Scholar 

  70. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.

    Article  PubMed  CAS  Google Scholar 

  71. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806–17.

    Article  PubMed  CAS  Google Scholar 

  72. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.

    Article  PubMed  CAS  Google Scholar 

  73. The WASH study steering committee and investigators. The WASH study (Warfarin /Aspirin Study in Heart failure): rationale, design and endpoints. Eur J Heart Fail. 1999;1:95–9.

    Article  Google Scholar 

  74. Cleland JGF, 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;148:157–64.

    Article  PubMed  CAS  Google Scholar 

  75. Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Eur J Heart Fail. 2006;8(4):428–32.

    Article  PubMed  CAS  Google Scholar 

  76. Massie B, 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(12):1616–24.

    Article  PubMed  CAS  Google Scholar 

  77. Pullicino P, Thompson JL, Barton B, Levin B, Graham S, Freudenberger RS. Warfarin versus aspirin in patients with reduced cardiac ejection (WARCEF): rationale, objectives, and design. J Card Fail. 2006;12(1):39–46.

    Article  PubMed  CAS  Google Scholar 

  78. Shelton RJ, Clark AL, Kaye GC, Cleland JGF. The atrial fibrillation paradox of heart failure. Congest Heart Fail. 2010;16(1):3–9.

    Article  PubMed  CAS  Google Scholar 

  79. Carson PE, Johnson GR, Dunkman WB, Fletcher RD, Farrell L, Cohn JN. The influence of atrial fibrillation on prognosis in mild to moderate heart failure: The V-HeFT studies. Circulation. 1993;87:VI102–10.

    PubMed  CAS  Google Scholar 

  80. Swedberg K, Olsson LG, Charlesworth A, et al. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J. 2005;26:1303–8.

    Article  PubMed  CAS  Google Scholar 

  81. Cleland JGF, Cowburn PJ, Falk RH. Should all patients with atrial fibrillation receive warfarin? Evidence from randomised clinical trials. Eur Heart J. 1996;17:674–81.

    Article  PubMed  CAS  Google Scholar 

  82. Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903–12.

    Article  PubMed  CAS  Google Scholar 

  83. Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360(20):2066–78.

    Article  PubMed  Google Scholar 

  84. Diener H-C, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:331–7.

    Article  PubMed  CAS  Google Scholar 

  85. Alikhan R, Cohen AT, Combe S, et al. Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood Coagul Fibrinolysis. 2003;14(4):341–6.

    Article  PubMed  CAS  Google Scholar 

  86. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011;365(23):2167–77.

    Article  PubMed  CAS  Google Scholar 

  87. Alikhan R, Cohen AT. Heparin for the prevention of venous thromboembolism in general medical patients (excluding stroke and myocardial infarction). Cochrane Database Syst Rev. 2009;(3):CD003747.

  88. Samama MM, Cohen AT, Darmon J-Y, et al. A comparison of enxoaparin with placebo for the prevention of venous thromboembolismin acutely ill medical patients. N Engl J Med. 1999;341:793–800.

    Article  PubMed  CAS  Google Scholar 

  89. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or clacium channel blocker versus diuretic (ALLHAT). JAMA. 2002;288:2981–97.

    Article  Google Scholar 

  90. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–28.

    Article  PubMed  CAS  Google Scholar 

  91. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997;350:757–64.

    Article  PubMed  CAS  Google Scholar 

  92. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9.

    Google Scholar 

  93. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23–33.

    Article  Google Scholar 

  94. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–35.

    Article  PubMed  CAS  Google Scholar 

  95. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294(19):2437–45.

    Article  PubMed  CAS  Google Scholar 

  96. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–30.

    Article  PubMed  CAS  Google Scholar 

  97. Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72.

    Article  PubMed  CAS  Google Scholar 

  98. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.

    Article  Google Scholar 

  99. Yusuf S, Nicklas JM, Timmis G, et al. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327:685–91.

    Article  Google Scholar 

  100. Yusuf S. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293–302.

    Article  Google Scholar 

  101. Poole-Wilson PA, Swedberg K, Cleland JGF, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362:7–13.

    Article  PubMed  CAS  Google Scholar 

  102. Remme W, Torp-Pedersen C, Cleland JG, et al. Carvedilol protects better against vascular events than Metoprolol in Heart Failure. Results from COMET. J Am Coll Cardiol. 2007;49(9):963–71.

    Article  PubMed  CAS  Google Scholar 

  103. Young JB, Dunlap ME, et al. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction results of the CHARM Low–left ventricular ejection fraction trials. Circulation. 2004;110:2618–26.

    Article  PubMed  CAS  Google Scholar 

  104. Solomon SD, Wang D, Finn P, et al. Effect of Candesartan on cause-specific mortality in heart failure patients. The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Program. Circulation. 2004;110:2180–3.

    Article  PubMed  CAS  Google Scholar 

  105. Cleland JG, McMurray JJ, Kjekshus J, et al. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J Am Coll Cardiol. 2009;54(20):1850–9.

    Article  PubMed  CAS  Google Scholar 

  106. Massie BM, Carson PE, McMurray JJ et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 November 11

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Disclosure

Conflicts of interest: J.G.F. Cleland: has received a substantial grant from the National Health Service Health Technology Assessment fund to run a trial comparing aspirin and clopidogrel (CACHE); and has received payment for advice on antithrombotic therapies from Johnson & Johnson, Boehringer-Ingelheim, and MSD.; S. Mumtaz: none; L. Cecchini: none.

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  1. Department of Cardiology, Hull York Medical School (University of Hull), Castle Hill Hospital, Kingston-upon-Hull, East Riding of Yorkshire, England, UK, HU16 5JQ

    John G. F. Cleland, Saqib Mumtaz & Luca Cecchini

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  1. John G. F. Cleland
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Correspondence to John G. F. Cleland.

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Cleland, J.G.F., Mumtaz, S. & Cecchini, L. Role of Antithrombotic Agents in Heart Failure. Curr Cardiol Rep 14, 314–325 (2012). https://doi.org/10.1007/s11886-012-0266-x

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