Cardiovascular Drugs and Therapy

, Volume 20, Issue 4, pp 295–308 | Cite as

Efficacy of Angiotensin Receptor Blockers in Cardiovascular Disease

  • Aldo P. Maggioni


The cardiovascular continuum describes the progression of pathophysiologic events from cardiovascular risk factors to symptomatic cardiovascular disease (CVD) and life-threatening events. Pharmacologic intervention early in the continuum may prevent or slow CVD development and improve quality of life. The renin–angiotensin–aldosterone system (RAAS) is central to the pathophysiology of CVD at many stages of the continuum. Numerous clinical trials of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have shown that RAAS blockade provides benefits to patients across the continuum. ARBs are as effective as ACE inhibitors in the treatment of hypertension; however tolerability and adherence to therapy appear to be improved with ARBs. Large clinical trials have shown that ARBs may provide therapeutic benefits beyond blood pressure control in patients with diabetes, heart failure or at risk of heart failure following a myocardial infarction. In addition, ARBs have been shown to provide protective effects in patients with impaired renal function or left ventricular hypertrophy. Additional clinical trials are ongoing to further characterize the role of ARBs in CVD management.

Key words

renin–angiotensin–aldosterone system angiotensin receptor blockers ACE inhibitors hypertension new-onset diabetes diabetic nephropathy atrial fibrillation myocardial infarction heart failure 


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  1. 1.
    World Health Organization. Cardiovascular disease: prevention and control, World Health Organization. (Accessed July 2005).Google Scholar
  2. 2.
    Petersen S, Peto V, Rayner M, Leal J, Luengo-Fernandez R, Gray A. European cardiovascular disease statistics, 2005 edition. European Heart Network and British Heart Foundation. Available from URL:
  3. 3.
    American Heart Association 2006, Heart disease and stroke statistics—2006 update, National Center, Dallas, Texas. Available from URL:
  4. 4.
    Dzau V, Braunwald E. Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement. Am Heart J 1991;121:1244–63.PubMedCrossRefGoogle Scholar
  5. 5.
    Dzau V. The cardiovascular continuum and renin–angiotensin–aldosterone system blockade. J Hypertens 2005;23(Suppl. 1):9–17.CrossRefGoogle Scholar
  6. 6.
    International Diabetes Federation. The Diabetes Atlas (e-Atlas), 2005.Google Scholar
  7. 7.
    Schmieder RE. Mechanisms for the clinical benefits of angiotensin II receptor blockers. Am J Hypertens 2005;18:720–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Carey RM, Siragy HM. Newly recognized components of the renin–angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev 2003;24:261–71.PubMedCrossRefGoogle Scholar
  9. 9.
    Maggioni AP, Latini R. The angiotensin-receptor blockers: from antihypertensives to cardiovascular all-round medications in 10 years? Blood Press 2002;11:328–38.PubMedCrossRefGoogle Scholar
  10. 10.
    Martin J, Krum H. Role of valsartan and other angiotensin receptor blocking agents in the management of cardiovascular disease. Pharmacol Res 2002;46:203–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Weber MA. The angiotensin II receptor blockers: opportunities across the spectrum of cardiovascular disease. Rev Cardiovasc Med 2002;3:183–91.PubMedCrossRefGoogle Scholar
  12. 12.
    Semple PF. Putative mechanisms of cough after treatment with angiotensin converting enzyme inhibitors. J Hypertens 1995;13(Suppl.):17–21.CrossRefGoogle Scholar
  13. 13.
    Dicpinigaitis PV. Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl.):169S–73S.PubMedCrossRefGoogle Scholar
  14. 14.
    Ravid D, Lishner M, Lang R, Ravid M. Angiotensin-converting enzyme inhibitors and cough: a prospective evaluation in hypertension and in congestive heart failure. J Clin Pharmacol 1994;34:1116–20.PubMedGoogle Scholar
  15. 15.
    Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995–1003.PubMedCrossRefGoogle Scholar
  16. 16.
    Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003;21:875–86.PubMedCrossRefGoogle Scholar
  17. 17.
    Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004;363:2022–31.PubMedCrossRefGoogle Scholar
  18. 18.
    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker versus diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981–97.CrossRefGoogle Scholar
  19. 19.
    Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999;353:611–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851–60.PubMedCrossRefGoogle Scholar
  21. 21.
    Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861–9.PubMedCrossRefGoogle Scholar
  23. 23.
    UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998;317:713–20.Google Scholar
  24. 24.
    McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362:767–71.PubMedCrossRefGoogle Scholar
  25. 25.
    Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362:772–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial-the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667–75.PubMedCrossRefGoogle Scholar
  28. 28.
    Swedberg K, Eneroth P, Kjekshus J, Snapinn S. Effects of enalapril and neuroendocrine activation on prognosis in severe congestive heart failure (follow-up of the CONSENSUS trial). CONSENSUS Trial Study Group. Am J Cardiol 1990;66:40D–4D.PubMedCrossRefGoogle Scholar
  29. 29.
    NETWORK Investigators. Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison. Eur Heart J 1998;19:481–9.CrossRefGoogle Scholar
  30. 30.
    SOLVD Investigators. 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.CrossRefGoogle Scholar
  31. 31.
    Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;325:303–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893–906.PubMedCrossRefGoogle Scholar
  33. 33.
    McMurray J, Solomon S, Pieper K, et al. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J Am Coll Cardiol 2006;47:726–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Dickstein K, Kjekshus J, OPTIMAAL Steering Committee of the Optimal Study Group. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002;360:752–60.PubMedCrossRefGoogle Scholar
  35. 35.
    Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821–8.Google Scholar
  36. 36.
    Oral captopril versus placebo among 13,634 patients with suspected acute myocardial infarction: interim report from the Chinese Cardiac Study (CCS-1). Lancet 1995;345:686–7.Google Scholar
  37. 37.
    Swedberg K, Held P, Kjekshus J, Rasmussen K, Ryden L, Wedel H. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 1992;327:678–84.PubMedCrossRefGoogle Scholar
  38. 38.
    Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 1994;343:1115–22.Google Scholar
  39. 39.
    Borghi C, Marino P, Zardini P, Magnani B, Collatina S, Ambrosioni E. Post acute myocardial infarction: the Fosinopril in Acute Myocardial Infarction Study (FAMIS). Am J Hypertens 1997;10:247S–54S.PubMedCrossRefGoogle Scholar
  40. 40.
    ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995;345:669–85.CrossRefGoogle Scholar
  41. 41.
    Rutherford JD, Pfeffer MA, Moye LA, et al. Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators. Circulation 1994;90:1731–8.PubMedGoogle Scholar
  42. 42.
    Kober L, Torp-Pederson C, Carlsen JE, et al. A clinical trial of the angiotensin-converting enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 1995;333:1670–6.PubMedCrossRefGoogle Scholar
  43. 43.
    The EURopean Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA Study). Lancet 2003;362:782–8.CrossRefGoogle Scholar
  44. 44.
    Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145–53.PubMedCrossRefGoogle Scholar
  45. 45.
    Braunwald E, Domanski MJ, Fowler SE, et al. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004;351:2058–68.PubMedCrossRefGoogle Scholar
  46. 46.
    Black HR, Graff A, Shute D, et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril. J Hum Hypertens 1997;11:483–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Bremner AD, Baur M, Oddou-Stock P, Bodin F. Valsartan: long-term efficacy and tolerability compared to lisinopril in elderly patients with essential hypertension. Clin Exp Hypertens 1997;19:1263–85.PubMedCrossRefGoogle Scholar
  48. 48.
    Chiou KR, Chen CH, Ding PY, et al. Randomized, double-blind comparison of irbesartan and enalapril for treatment of mild to moderate hypertension. Zhonghua YiXue ZaZhi (Taipei) 2000;63:368–76.Google Scholar
  49. 49.
    Chowta KN, Chowta MN, Bhat P, Adhikari PM. An open comparative clinical trial to assess the efficacy and safety of losartan versus enalapril in mild to moderate hypertension. J Assoc Phys India 2002;50:1236–9.Google Scholar
  50. 50.
    Coca A, Calvo C, Garcia-Puig J, et al. A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorizacion Ambulatoria Presion Arterial APROVEL). Clin Ther 2002;24:126–38.PubMedCrossRefGoogle Scholar
  51. 51.
    Fagard R, Lijnen P, Pardaens K, Thijs L, Vinck W. A randomised, placebo-controlled, double-blind, crossover study of losartan and enalapril in patients with essential hypertension. J Hum Hypertens 2001;15:161–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Fogari R, Mugellini A, Zoppi A, et al. Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension. Eur J Clin Pharmacol 2004;59:863–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Himmelmann A, Keinanen-Kiukaanniemi S, Wester A, et al. The effect duration of candesartan cilexetil once daily, in comparison with enalapril once daily, in patients with mild to moderate hypertension. Blood Press 2001;10:43–51.PubMedCrossRefGoogle Scholar
  54. 54.
    Holwerda NJ, Fogari R, Angeli P, et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril. J Hypertens 1996;14:1147–51.PubMedCrossRefGoogle Scholar
  55. 55.
    Malacco E, Santonastaso M, Vari NA, et al. Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study. Clin Ther 2004;26:855–65.PubMedCrossRefGoogle Scholar
  56. 56.
    Mallion JM, Boutelant S, Chabaux P, et al. Valsartan, a new angiotensin II antagonist; blood pressure reduction in essential hypertension compared with an angiotensin converting enzyme inhibitor, enalapril. Blood Press Monit 1997;2:179–84.PubMedGoogle Scholar
  57. 57.
    Mimran A, Ruilope L, Kerwin L, et al. A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension. J Hum Hypertens 1998;12:203–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Wu SC, Liu CP, Chiang HT, Lin SL. Prospective and randomized study of the antihypertensive effect and tolerability of three antihypertensive agents, losartan, amlodipine, and lisinopril, in hypertensive patients. Heart Vessels 2004;19:13–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Zanchetti A, Omboni S. Comparison of candesartan versus enalapril in essential hypertension. Italian Candesartan Study Group. Am J Hypertens 2001;14:129–34.PubMedCrossRefGoogle Scholar
  60. 60.
    Willenheimer R, Helmers C, Pantev E, et al. Safety and efficacy of valsartan versus enalapril in heart failure patients. Int J Cardiol 2002;85:261–70.PubMedCrossRefGoogle Scholar
  61. 61.
    Dina R, Jafari M. Angiotensin II-receptor antagonists: an overview. Am J Health Syst Pharm 2000;57:1231–41.PubMedGoogle Scholar
  62. 62.
    Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997;349:747–52.PubMedCrossRefGoogle Scholar
  63. 63.
    Pylypchuk GB. ACE inhibitor-versus angiotensin II blocker-induced cough and angioedema. Ann Pharmacother 1998;32:1060–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Hansson L. ‘Why don’t you do as I tell you?’ Compliance and antihypertensive regimens. Int J Clin Pract 2002;56:191–6.PubMedGoogle Scholar
  65. 65.
    Wogen J, Kreilick CA, Livornese RC, et al. Patient adherence with amlodipine, lisinopril, or valsartan therapy in a usual-care setting. J Manag Care Pharm 2003;9:424–9.PubMedGoogle Scholar
  66. 66.
    Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:1004–10.PubMedCrossRefGoogle Scholar
  67. 67.
    Dornhorst A, Powell SH, Pensky J. Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion. Lancet 1985;1:123–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Holzgreve H, Nakov R, Beck K, Janka HU. Antihypertensive therapy with verapamil SR plus trandolapril versus atenolol plus chlorthalidone on glycemic control. Am J Hypertens 2003;16:381–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Giugliano D, Acampora R, Marfella R, et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus and hypertension. A randomized, controlled trial. Ann Intern Med 1997;126:955–9.PubMedGoogle Scholar
  70. 70.
    Torp-Pedersen C, Poole-Wilson PA, Swedberg K, et al. Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure-COMET. Am Heart J 2005;149:370–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Yusuf S, Ostergren JB, Gerstein HC, et al. Effects of candesartan on the development of a new diagnosis of diabetes in patients with heart failure. Circulation 2005;112:48–53.PubMedCrossRefGoogle Scholar
  72. 72.
    Gerstein HC, Yusuf S, Holman R, Bosch J, Pogue J, The DREAM Trial Investigators. Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia 2004;47:1519–27.PubMedCrossRefGoogle Scholar
  73. 73.
    Viberti G, Wheeldon NM, MicroAlbuminuria Reduction with VALsartan (MARVAL) Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002;106:672–8.PubMedCrossRefGoogle Scholar
  74. 74.
    EUCLID Study Group. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID Study Group. Lancet 1997;349:1787–92.CrossRefGoogle Scholar
  75. 75.
    Baba S, J-MIND Study Group. Nifedipine and enalapril equally reduce the progression of nephropathy in hypertensive type 2 diabetics. Diabetes Res Clin Pract 2001;54:191–201.PubMedCrossRefGoogle Scholar
  76. 76.
    Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000;355:253–9.CrossRefGoogle Scholar
  77. 77.
    Barnett AH, Bain SC, Bouter P, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004;351:1952–61.PubMedCrossRefGoogle Scholar
  78. 78.
    Daoud EG, Marcovitz P, Knight BP, et al. Short-term effect of atrial fibrillation on atrial contractile function in humans. Circulation 1999;99:3024–7.PubMedGoogle Scholar
  79. 79.
    Kochiadakis GE, Igoumenidis NE, Marketou ME, Solomou MC, Kanoupakis EM, Vardas PE. Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Am J Cardiol 1998;81:995–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Southworth MR, Zarembski D, Viana M, Bauman J. Comparison of sotalol versus quinidine for maintenance of normal sinus rhythm in patients with chronic atrial fibrillation. Am J Cardiol 1999;83:1629–32.PubMedCrossRefGoogle Scholar
  81. 81.
    Shi Y, Li D, Tardif JC, Nattel S. Enalapril effects on atrial remodeling and atrial fibrillation in experimental congestive heart failure. Cardiovasc Res 2002;54:456–61.PubMedCrossRefGoogle Scholar
  82. 82.
    Kumagai K, Nakashima H, Urata H, Gondo N, Arakawa K, Saku K. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003;41:2197–204.PubMedCrossRefGoogle Scholar
  83. 83.
    Li D, Shinagawa K, Pang L, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation 2001;104:2608–14.PubMedGoogle Scholar
  84. 84.
    Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 2000;101:2612–7.PubMedGoogle Scholar
  85. 85.
    Pedersen OD, Bagger H, Kober L, Torp-Pedersen C. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999;100:376–80.PubMedGoogle Scholar
  86. 86.
    Wachtell K, Lehto M, Gerdts E, et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol 2005;45:712–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation 2002;106:331–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Ueng KC, Tsai TP, Yu WC, et al. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of longstanding persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J 2003;24:2090–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Maggioni AP, Latini R, Carson PE, et al., for the Val-HeFT Investigators. Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT). Am Heart J 2005;149:548–57.PubMedCrossRefGoogle Scholar
  90. 90.
    Ducharme A, Swedberg K, Pfeffer MA, et al. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J 2006;151:985–91.PubMedCrossRefGoogle Scholar
  91. 91.
    Zimmermann M, Unger T. Challenges in improving prognosis and therapy: the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial programme. Expert Opin Pharmacother 2004;5:1201–18.PubMedCrossRefGoogle Scholar
  92. 92.
    Disertori M, Latini R, Maggioni AP, et al. Rationale and design of the GISSI-Atrial Fibrillation Trial: a randomized, prospective, multicenter study on the use of valsartan, an angiotensin II AT1-receptor blocker, in the prevention of atrial fibrillation recurrence. J Cardiovasc Med 2006;7:29–38.CrossRefGoogle Scholar
  93. 93.
    Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ 2004;329:1248–9.PubMedCrossRefGoogle Scholar
  94. 94.
    McMurray JJ. Angiotensin receptor blockers and myocardial infarction. Analysis of evidence is incomplete and inaccurate. BMJ 2005;330:1269.PubMedCrossRefGoogle Scholar
  95. 95.
    Opie LH. Angiotensin receptor blockers and myocardial infarction. Direct comparative studies are needed. BMJ 2005;330:1270.PubMedCrossRefGoogle Scholar
  96. 96.
    Verdecchia P, Angeli F, Gattobigio R, Reboldi GP. Do angiotensin II receptor blockers increase the risk of myocardial infarction? Eur Heart J 2005;26:2381–6.PubMedCrossRefGoogle Scholar
  97. 97.
    Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet 2004;19(363):2049–51.CrossRefGoogle Scholar
  98. 98.
    Teo K, Yusuf S, Sleight P, et al. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J 2004;148:52–61.PubMedCrossRefGoogle Scholar
  99. 99.
    Maggioni AP, Anand I, Gottlieb SO, et al. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 2002;40:1414–21.PubMedCrossRefGoogle Scholar
  100. 100.
    Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362:759–66.PubMedCrossRefGoogle Scholar
  101. 101.
    Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003;362:777–81.PubMedCrossRefGoogle Scholar
  102. 102.
    Swedberg K, Cleland J, Dargie H, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). Eur Heart J 2005;26:1115–40.PubMedCrossRefGoogle Scholar

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© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  1. 1.ANMCO Research CenterItalian Association of Hospital CardiologistsFlorenceItaly

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