Current Cardiology Reports

, Volume 8, Issue 3, pp 217–225 | Cite as

The problem of polypharmacy in heart failure



Improvements in the medical therapy for chronic heart failure have led to a dramatic decrease in the morbidity and mortality of patients with heart failure over the past two decades. This improvement has been gained at the expense of an increasing number of potent drugs that heart failure patients have to take chronically. Because heart failure forms the end-stage of different cardiovascular diseases and their predisposing risk factors, patients need drug treatment not only for heart failure itself but also for related conditions. Even more, because most heart failure patients are elderly, a number of unrelated, noncardiovascular diseases become apparent, which further increase the number of pharmaceutical substances with which heart failure patients are treated. The resulting polypharmacy leads to problems including economic burden, patient compliance, and most importantly, partly unpredictable drug interactions. This article reviews the existing data concerning some of these problems, to provide an aid for choosing the appropriate drugs in heart failure patients and minimizing the patient’s risk.


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References and Recommended Reading

  1. 1.
    Withering W: An Account of the Foxglove and Some of its Medicinal Uses. London: J and J Robinson; 1785.Google Scholar
  2. 2.
    Group DTDI: The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997, 336:525–533.CrossRefGoogle Scholar
  3. 3.
    Schwinger RHG: Therapie der chronischen Herzinsuffizienz mit Diuretika. In Herzinsuffizienz. Edited by Erdmann E. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 2005:265–299.Google Scholar
  4. 4.
    Erdmann E: Therapie der Herzinsuffizienz mit ACE-Hemmern. In Herzinsuffizienz. Edited by Erdmann E. Stuttgart: Wissenschaftiche Verlagsgesellschaft; 2005:314–326.Google Scholar
  5. 5.
    Erdmann E: Therapie der chronischen Herzinsuffizienz mit Beta-Blockern. In Herzinsuffizienz. Edited by Erdmann E. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 2005:386–395.Google Scholar
  6. 6.
    Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717.PubMedCrossRefGoogle Scholar
  7. 7.
    Pitt B, Remme W, Zannad F, et al.: Eplerenone Post-Acute Myocardial Infarction Heart Failure E, Survival Study I. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321.PubMedCrossRefGoogle Scholar
  8. 8.
    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, 355:1582–1587.PubMedCrossRefGoogle Scholar
  9. 9.
    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, 362:772–776.PubMedCrossRefGoogle Scholar
  10. 10.
    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, 362:767–771.PubMedCrossRefGoogle Scholar
  11. 11.
    Swedberg K, Cleland J, Dargie H, et al.: Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 2005, 26:1115–1140.PubMedCrossRefGoogle Scholar
  12. 12.
    Hunt SA: American College of Cardiology, American Heart Association Task Force on Practice Guidelines. 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 (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005, 46:e1-e82.PubMedCrossRefGoogle Scholar
  13. 13.
    Taylor AL, Ziesche S, Yancy C, et al.: African-American Heart Failure Trial I. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004, 351:2049–2057.PubMedCrossRefGoogle Scholar
  14. 14.
    Komajda M, Lapuerta P, Hermans N, et al.: Adherence to guidelines is a predictor of outcome in chronic heart failure: the MAHLER survey. Eur Heart J 2005, 26:1653–1659. Detailed analysis of guideline adherence by cardiologists in the treatment of heart failure patients and its impact on morbidity and mortality.PubMedCrossRefGoogle Scholar
  15. 15.
    Flesch M, Komajda M, Lapuerta P, et al.: Leitliniengerechte Herzinsuffizienzbehandlung in Deutschland — Ergebnisse der MAHLER-Studie. Dtsch Med Wochenschr 2005, 130:2191–2197.PubMedCrossRefGoogle Scholar
  16. 16.
    Masoudi FA, Rathore SS, Wang Y, et al.: National patterns of use and effectiveness of angiotensin-converting enzyme inhibitors in older patients with heart failure and left ventricular systolic dysfunction. Circulation 2004, 110:724–731.PubMedCrossRefGoogle Scholar
  17. 17.
    Masoudi FA, Baillie CA, Wang Y, et al.: The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998-2001. Arch Intern Med 2005, 165:2069–2076. Most detailed available study on heart failure medications and on comedications for other diseases in CHF patients in the United States.PubMedCrossRefGoogle Scholar
  18. 18.
    Cohn JN, Tognoni G: Valsartan Heart Failure Trial I. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001, 345:1667–1675.PubMedCrossRefGoogle Scholar
  19. 19.
    Jong P, Demers C, McKelvie RS, Liu PP: Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol 2002, 39:463–470.PubMedCrossRefGoogle Scholar
  20. 20.
    The Cardiac Insufficiency Bisoprolol Study II (CIBIS II): a randomised trial. Lancet 1999, 359:9–13.Google Scholar
  21. 21.
    Effect of metoprolol CR/XL in chronic heart failure. Lancet 1999, 353:2001–2007.Google Scholar
  22. 22.
    Cowper PA, DeLong ER, Whellan DJ, et al.: Economic effects of beta-blocker therapy in patients with heart failure. Am J Med 2004, 116:104–111.PubMedCrossRefGoogle Scholar
  23. 23.
    Stewart S, McMurray JJ, Hebborn A, et al.: Carvedilol reduces the costs of medical care in severe heart failure: an economic analysis of the COPERNICUS study applied to the United Kingdom. Int J Cardiol 2005, 100:143–149.PubMedCrossRefGoogle Scholar
  24. 24.
    Stehlik J, Taylor DO: And an ARB makes nine: polypharmacy in patients with heart failure. Cleve Clin J Med 2004, 71:674–677.PubMedCrossRefGoogle Scholar
  25. 25.
    Yusuf S, Ostergren JB, Gerstein HC, et al.: Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure. Circulation 2005, 112:48–53.PubMedCrossRefGoogle Scholar
  26. 26.
    Flather MD, Shibata MC, Coats AJ, et al.: Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005, 26:215–225.PubMedCrossRefGoogle Scholar
  27. 27.
    Packer M, Coats AJ, Fowler MB, et al.: Carvedilol Prospective Randomized Cumulative Survival Study G. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001, 344:1651–1658.PubMedCrossRefGoogle Scholar
  28. 28.
    Wikstrand J, Hjalmarson A, Waagstein F, et al.: Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF). J Am Coll Cardiol 2002, 40:491–498.PubMedCrossRefGoogle Scholar
  29. 29.
    Gottlieb SS, Fisher ML, Kjekshus J, et al.: Tolerability of betablocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Circulation 2002, 105:1182–1188.PubMedCrossRefGoogle Scholar
  30. 30.
    Delles C, Schmieder RE: The kidney in congestive heart failure: renal adverse event rate of treatment. J Cardiovasc Pharmacol 2001, 38:99–107.PubMedCrossRefGoogle Scholar
  31. 31.
    Pfeffer MA, McMurray JJ, Velazquez EJ, et al.: Valsartan in Acute Myocardial Infarction Trial I. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003, 349:1893–1906.PubMedCrossRefGoogle Scholar
  32. 32.
    Juurlink DN, Mamdani MM, Lee DS, et al.: Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004, 351:543–551. Study pointing out how and why an unreflected transfer of clinical trial results into daily praxis can lead to an unfortunate outcome.PubMedCrossRefGoogle Scholar
  33. 33.
    Havranek EP, Masoudi FA, Westfall KA, et al.: Spectrum of heart failure in older patients: results from the National Heart Failure project. Am Heart J 2002, 143:412–417.PubMedCrossRefGoogle Scholar
  34. 34.
    Amabile CM, Spencer AP: Keeping your patient with heart failure safe: a review of potentially dangerous medications [erratum appears in Arch Intern Med 2004, 164:1464]. Arch Intern Med 2004, 164:709–720. Excellent review on drug side effects and on interactions of substances commonly used in heart failure patients.PubMedCrossRefGoogle Scholar
  35. 35.
    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.PubMedCrossRefGoogle Scholar
  36. 36.
    Nawarskas JJ, Spinler SA: Update on the interaction between aspirin and angiotensin-converting enzyme inhibitors. Pharmacotherapy 2000, 20:698–710.PubMedCrossRefGoogle Scholar
  37. 37.
    Page J, Henry D: Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. Arch Intern Med 2000, 160:777–784.PubMedCrossRefGoogle Scholar
  38. 38.
    Whelton A, Fort JG, Puma JA, et al.: Cyclooxygenase- 2-specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Therapeut 2001, 8:85–95.CrossRefGoogle Scholar
  39. 39.
    Packer M, O’Connor CM, Ghali JK, et al.: Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.N Engl J Med 1996, 335:1107–1114.PubMedCrossRefGoogle Scholar
  40. 40.
    Cohn JN, Ziesche S, Smith R, et al.: Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group. Circulation 1997, 96:856–863.PubMedGoogle Scholar
  41. 41.
    Elkayam U, Amin J, Mehra A, et al.: A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation 1990, 82:1954–1961.PubMedGoogle Scholar
  42. 42.
    Cohn JN, Pfeffer MA, Rouleau J, et al.: Adverse mortality effect of central sympathetic inhibition with sustainedrelease moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail 2003, 5:659–667.PubMedCrossRefGoogle Scholar
  43. 43.
    Kjekshus J, Dunselman P, Blideskog M, et al.: A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): study design and baseline characteristics. Eur J Heart Fail 2005, 7:1059–1069.PubMedCrossRefGoogle Scholar
  44. 44.
    Mettauer B, Rouleau JL, Burgess JH: Detrimental arrhythmogenic and sustained beneficial hemodynamic effects of oral salbutamol in patients with chronic congestive heart failure. Am Heart J 1985, 109:840–847.PubMedCrossRefGoogle Scholar
  45. 45.
    Bouvy ML, Heerdink ER, De Bruin ML, et al.: Use of sympathomimetic drugs leads to increased risk of hospitalization for arrhythmias in patients with congestive heart failure. Arch Intern Med 2000, 160:2477–3480.PubMedCrossRefGoogle Scholar
  46. 46.
    Webb DJ, Freestone S, Allen MJ, Muirhead GJ: Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol 1999, 83:21C-28C.PubMedCrossRefGoogle Scholar
  47. 47.
    Leibovitz A, Bilchinsky T, Gil I, Habot B: Elevated serum digoxin level associated with coadministered fluoxetine. Arch Intern Med 1998, 158:1152–1153.PubMedCrossRefGoogle Scholar
  48. 48.
    Fowles RE, Cloward TV, Yowell RL: Endocardial fibrosis associated with fenfluramine-phentermine. N Engl J Med 1998, 338:1316.PubMedCrossRefGoogle Scholar
  49. 49.
    Kottkamp H, Budde T, Lamp B, et al.: Clinical significance and management of ventricular arrhythmias in heart failure. Eur Heart J 1994, 15(Suppl D):155–163.PubMedGoogle Scholar
  50. 50.
    Echt DS, Liebson PR, Mitchell LB, et al.: Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991, 324:781–788.PubMedCrossRefGoogle Scholar
  51. 51.
    Hallstrom AP, Anderson JL, Carlson M, et al.: Time to arrhythmic, ischemic, and heart failure events: exploratory analyses to elucidate mechanisms of adverse drug effects in the Cardiac Arrhythmia Suppression Trial. Am Heart J 1995, 130:71–79.PubMedCrossRefGoogle Scholar
  52. 52.
    Flaker GC, Blackshear JL, McBride R, et al.: Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 1992, 20:527–532.PubMedCrossRefGoogle Scholar
  53. 53.
    Waldo AL, Camm AJ, deRuyter H, et al.: Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet 1996, 348:7–12.PubMedCrossRefGoogle Scholar
  54. 54.
    Bardy GH, Lee KL, Mark DB, et al.: Sudden Cardiac Death in Heart Failure Trial I. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005, 352:225–237.PubMedCrossRefGoogle Scholar
  55. 55.
    Straus SM, Sturkenboom MC, Bleumink GS, et al.: Noncardiac QTc-prolonging drugs and the risk of sudden cardiac death. Eur Heart J 2005, 26:2007.PubMedCrossRefGoogle Scholar
  56. 56.
    Rathore SS, Wang Y, Krumholz HM: Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med 2002, 347:1403–1411.PubMedCrossRefGoogle Scholar
  57. 57.
    Drici MD, Clement N: Is gender a risk factor for adverse drug reactions? The example of drug-induced long QT syndrome. Drug Saf 2001, 24:575–585.PubMedCrossRefGoogle Scholar
  58. 58.
    Mann DL, McMurray JJ, Packer M, et al.: Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004, 109:1594–1602.PubMedCrossRefGoogle Scholar
  59. 59.
    Packer M, Califf RM, Konstam MA, et al.: Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation 2002, 106:920–926.PubMedCrossRefGoogle Scholar
  60. 60.
    Packer M, McMurray J, Massie BM, et al.: Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. J Card Fail 2005, 11:12–20.PubMedCrossRefGoogle Scholar
  61. 61.
    Flesch M, Hoper A, Dell’Italia L, et al.: Activation and functional significance of the renin-angiotensin system in mice with cardiac restricted overexpression of tumor necrosis factor. Circulation 2003, 108:598–604.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  1. 1.Klinik III für Innere Medizinder Universität zu KölnKölnGermany

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