Current Heart Failure Reports

, Volume 4, Issue 2, pp 110–116

Tips and tricks on outpatient initiation and uptitration of beta-blockade in heart failure



β-blockade has a therapeutic role across the continuum of patients with heart failure (HF), with a demonstrated mortality benefit in stage II and III HF. Concerns regarding initiation and uptitration linger as patients with resting bradycardia, pulmonary, or vascular disease are often unnecessarily excluded from receiving therapy. We will review the risk data on β-blockade and offer therapeutic strategies to help overcome residual barriers to the initiation and uptitration of this important therapy in patients with HF.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Hunt SA, 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): ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult. J Am Coll Cardiol 2005, 46:e1–e82.PubMedCrossRefGoogle Scholar
  2. 2.
    Fonarow GC, ADHERE Scientific Advisory Committee: The acute decompensated heart failure national registry (ADHERE): opportunities to improve care of patients hospitalized with acute decompensated heart failure. Rev Cardiovasc Med 2003, 4(Suppl 7):S21–30.PubMedGoogle Scholar
  3. 3.
    Packer M, Bristow MR, Cohn JN, et al.: The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996, 343:1349–1355.CrossRefGoogle Scholar
  4. 4.
    Franciosa JA, Massie BM, Lukas MA, et al.: β-blocker therapy for heart failure outside the clinical trial setting: findings of a community-based registry. Am Heart J 2004, 148:718–726.PubMedCrossRefGoogle Scholar
  5. 5.
    Ko DT, Hebert PR, Coffey CS, et al.: Adverse effects of β-blocker therapy for patients with HF: a quantitative overview of randomized trials. Arch Intern Med 2004, 164:1389–1394.PubMedCrossRefGoogle Scholar
  6. 6.
    Gattis WA, O’Connor CM, Gallup DS, et al.: Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure. J Am Coll Cardiol 2004, 43:1534–1541.PubMedCrossRefGoogle Scholar
  7. 7.
    Spaeder JA, Najjar SS, Gerstenblith G, et al.: Rapid titration of carvedilol in patients with congestive heart failure: a randomized trial of automated telemedicine versus frequent outpatient clinic visits. Am Heart J 2006, 151:844.e1–e10.CrossRefGoogle Scholar
  8. 8.
    Packer M, Poole-Wilson PA, Armstrong PW, et al.: Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation 1999, 100:2312–2318.PubMedGoogle Scholar
  9. 9.
    Taylor AL, Ziesche S, Yancy C, et al.: Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004, 351:2049–2057.PubMedCrossRefGoogle Scholar
  10. 10.
    Shakar SF, Abraham WT, Gilbert WM, et al.: Combined oral positive inotropic and beta-blocker therapy for treatment of refractory Class IV heart failure. J Am Coll Cardiol 1998, 31:1336–1340.PubMedCrossRefGoogle Scholar
  11. 11.
    Kumar A, Choudhary G, Antonio C, et al.: Carvedilol titration in patients with congestive heart failure receiving inotropic therapy. Am Heart J 2001, 142:512–515.PubMedCrossRefGoogle Scholar
  12. 12.
    Epstein SE, Braunwald E: The effect of beta adrenergic blockade on patterns of urinary sodium excretion. Ann Intern Med 1966, 65:20–27.PubMedGoogle Scholar
  13. 13.
    Weil JV, Chidsey CA: Plasma volume expansion resulting from interference with adrenergic function in normal man. Circulation 1968, 37:54–61.PubMedGoogle Scholar
  14. 14.
    Packer M, Coats AJS, Fowler MB, et al.: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001, 344:1651–1658.PubMedCrossRefGoogle Scholar
  15. 15.
    Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet 1999, 353:2001–2007.Google Scholar
  16. 16.
    A randomized trial of beta-blockade in heart failure: the cardiac insufficiency bisoprolol study (CIBIS). CIBIS investigators and committees. Circulation 1994, 90:1765–1773.Google Scholar
  17. 17.
    The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999, 353:9–13.Google Scholar
  18. 18.
    Beta-blocker Evaluation of Survival Trial Investigators: A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001, 344:1659–1667.CrossRefGoogle Scholar
  19. 19.
    Effects of metoprolol CR in patients with ischemic and dilated cardiomyopathy: the randomized evaluation of strategies for left ventricular dysfunction pilot study. Circulation 2000, 101:378–384.Google Scholar
  20. 20.
    Gilbert EM, Abraham WT, Olsen S, et al.: Comparative hemodynamic, left ventricular functional, and anti-adrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation 1996, 94:2817–2825.PubMedGoogle Scholar
  21. 21.
    Nul D, Zambrano C, Diaz A, et al.: Impact of a standardized titration protocol with carvedilol in heart failure: safety, tolerability, and efficacy-a report from the GESICA registry. Cardiovasc Drugs Ther 2005, 18:125–134.CrossRefGoogle Scholar
  22. 22.
    Wilkoff BL, Cook JR, Epstein AE, et al.: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the dual chamber and VVI implantable defibrillator (DAVID) trial. JAMA 2002, 288:3115–3123.PubMedCrossRefGoogle Scholar
  23. 23.
    Stecker EC, Fendrick M, Knight BP, Aaronson KD: Prophylactic pacemaker use to allow β-blocker therapy in patients with chronic HF with bradycardia. Am Heart J 2006, 151:820–828.PubMedCrossRefGoogle Scholar
  24. 24.
    Heart Failure Society of America: HFSA 2006 comprehensive heart failure practice guideline. J Card Fail 2006, 12:e1–2.Google Scholar
  25. 25.
    Zewail AM, Nawar M, Vrtovec B, et al.: Intravenous milrinone in the treatment of advanced congestive HF. Tex Heart Inst J 2003, 30:109–113.PubMedGoogle Scholar
  26. 26.
    McKelvie RS, Teo KK, McCartney N, et al.: Effects of exercise training in patients with congestive HF: a critical review. J Am Coll Cardiol 1995, 25:789–796.PubMedCrossRefGoogle Scholar
  27. 27.
    Coats AJS, Adamopoulos S, Radaelli A, et al.: Controlled trial of physical training in chronic HF: exercise performance, hemodynamics, ventilation, and autonomic function. Circulation 1992, 85:2119–2131.PubMedGoogle Scholar
  28. 28.
    Jónsdóttir S, Andersen KK, Sigurðsson AF, Sigurðsson SB: The effect of physical training in chronic HF. Eur J Heart Fail 2006, 8:97–101.PubMedCrossRefGoogle Scholar
  29. 29.
    Forissier JF, Vernochet P, Bertrand P, et al.: Influence of carvedilol on the benefits of physical training in patients with moderate chronic HF. Eur J Heart Fail 2001, 3:335–342.PubMedCrossRefGoogle Scholar
  30. 30.
    Kukin ML, Kalman J, Charney RH, et al.: Prospective, randomized comparison of effect of long-term treatment with metoprolol or carvedilol on symptoms, exercise, ejection fraction, and oxidative stress in heart failure. Circulation 1999, 99:2645–2651.PubMedGoogle Scholar
  31. 31.
    Ko DT, Hebert PR, Coffey CS, et al.: β-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 2002, 288:351–357.PubMedCrossRefGoogle Scholar
  32. 32.
    Lue TF: Drug therapy: erectile dysfunction. N Engl J Med 2000, 342:1802–1813.PubMedCrossRefGoogle Scholar
  33. 33.
    Katz SD, Parker JD, Glasser DB, et al.: Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure. Am J Cardiol 2005, 95:36–42.PubMedCrossRefGoogle Scholar
  34. 34.
    Salpeter SR, Ormiston TM, Salpeter EE, et al.: Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis. Resp Med 2003, 97:1094–1101.CrossRefGoogle Scholar
  35. 35.
    Camsari A, Arikan S, Avan C, et al.: Metoprolol, a β1-selective blocker, can be used safely in coronary artery disease patients with chronic obstructive pulmonary disease. Heart Vessels 2003, 18:188–192.PubMedCrossRefGoogle Scholar
  36. 36.
    Barnett MJ, Milavetz G, Kaboli PJ: β-blocker therapy in veterans with asthma or chronic obstructive pulmonary disease. Pharmacotherapy 2005, 25:1550–1559.PubMedCrossRefGoogle Scholar
  37. 37.
    Kotlyar E, Keogh AM, Macdonald PS, et al.: Tolerability of carvedilol in patients with HF and concomitant chronic obstructive pulmonary disease or asthma. J Heart Lung Transpl 2002, 21:1290–1295.CrossRefGoogle Scholar
  38. 38.
    LeJemtel TH, Padeletti M, Jelic S: Diagnostic and therapeutic challenges in patients with coexistent and chronic obstructive pulmonary disease and congestive HF. J Am Coll Cardiol 2007, 49:171–180.CrossRefGoogle Scholar
  39. 39.
    Vale JA, Van de Pette SJ, Price TML: Peripheral gangrene complicating beta-blockade. Lancet 1977, 2:412.PubMedCrossRefGoogle Scholar
  40. 40.
    Vale JA, Jefferys DB: Peripheral gangrene complicating beta-blockade. Lancet 1978, 1:1216.PubMedCrossRefGoogle Scholar
  41. 41.
    Roberts DH, Tsao Y, McLoughlin GA, Breckenridge A: Placebo-controlled comparison of captopril, atenolol, labetalol, and pindolol in hypertension complicated by intermittent claudication. Lancet 1987, 2:650–653.PubMedCrossRefGoogle Scholar
  42. 42.
    Hiatt WR, Stoll S, Nies AS: Effect of β-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease. Circulation 1985, 72:1226–1231.PubMedGoogle Scholar
  43. 43.
    Radack K, Deck C: Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease: a meta-analysis of randomized controlled trials. Arch Intern Med 1991, 151:1769–1776.PubMedCrossRefGoogle Scholar
  44. 44.
    Ubbink DT, Verhaar EE, Lie HK, Legamate DA: Effect of β-blockers on peripheral skin microcirculation in hypertension and peripheral arterial disease. J Vasc Surg 2003, 38:535–540.PubMedCrossRefGoogle Scholar
  45. 45.
    Hirsch AT, Haskal ZJ, Hertzer NR: ACC/AHA guidelines for the management of patients with peripheral arterial disease. J Am Coll Cardiol 2005, 47:1239–1312.CrossRefGoogle Scholar
  46. 46.
    Mendelson G, Aronow WS: Underutilization of beta-blockers in older patients with prior myocardial infarction or coronary artery disease in an academic, hospital-based geriatrics practice. J Am Geriatric Soc 1997, 45:1360–1361.Google Scholar
  47. 47.
    Sinha S, Goldstein M, Penrod J, et al.: Brief report: β-blocker use among veterans with systolic HF. J Gen Intern Med 2006, 21:1306–1309.PubMedCrossRefGoogle Scholar
  48. 48.
    Deedwania P, Gottlieb S, Ghali JK, et al.: Efficacy, safety, and tolerability of β-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure. Eur Heart J 2004, 25:1300–1309.PubMedCrossRefGoogle Scholar
  49. 49.
    Hülsmann M, Berger R, Mörtl D, Pacher R: Influence of age and in-patient care on prescription rate and long-term outcome in chronic heart failure: a data-based substudy of the EuroHeart failure survey. Eur J Heart Fail 2005, 7:657–661.PubMedCrossRefGoogle Scholar
  50. 50.
    Lawless CE, Tamlyn T, Shah R, et al.: Titration of carvedilol in elderly HF patients. Am J Geriatr Cardiol 2005, 14:230–235.PubMedCrossRefGoogle Scholar
  51. 51.
    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
  52. 52.
    Gress TW, Nieto J, Shahar E, et al.: Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med 2000, 342:905–912.PubMedCrossRefGoogle Scholar
  53. 53.
    Bakris GL, Fonseca V, Katholi RE, et al.: Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes and hypertension: a randomized controlled trial. JAMA 2004, 292:2227–2236.PubMedCrossRefGoogle Scholar
  54. 54.
    Deedwania PC, Giles TD, Klibaner M, et al.: Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF. Am Heart J 2005, 149:159–167.PubMedCrossRefGoogle Scholar
  55. 55.
    Bell DS, Lukas MA, Holdbrook FK, Fowler MB: The effect of carvedilol on mortality risk in heart failure patients with diabetes: results of a meta-analysis. Curr Med Res Opin 2006, 22:287–296.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.New Jersey Medical SchoolUniversity of Medicine and Dentistry of New JerseyNewarkUSA

Personalised recommendations