Beta Blockers for Heart Failure
Beta blockers are used for hypertensive patients to protect against cardiovascular morbidity and mortality and were shown to be beneficial for other heart conditions.1 The 2013 guidelines for heart failure by the American College of Cardiology and the American Heart Association (ACC/AHA) recommend appropriate doses of specific beta blockers for patients with heart failure with reduced ejection fraction (HFrEF) to decrease the risk of death, hospitalizations, co-morbidities, symptoms, and coronary artery disease.2,3 In both the 2013 guidelines for heart failure and the 2017 guidelines for high blood pressure, the ACC/AHA list the beta blockers bisoprolol, metoprolol, and carvedilol as the preferred antihypertensive medications for patients with HFrEF.3,4 In addition to these guidelines, a systematic review found that beta blockers are beneficial for patients with heart failure.5 The review examined 22 studies of bisoprolol, bucindolol, carvedilol, metoprolol, and nebivolol treatment on patients with heart failure (n=10,480) and found that all-cause mortality was 35% lower in the beta blocker group (8.2%) than in the control group (13.3%) (odds ratio [OR] 0.65, 95% confidence interval [CI] [0.57 – 0.74], p<0.0001). Rate of hospitalization due to worsening heart failure was also lower in the beta blocker group (11.5%) when compared to the control groups (17.2%) (OR 0.63, 95% CI [0.56 – 0.71], p<0.0001). Combined all-cause mortality or hospital admission for heart failure was also lower in the beta blocker group (21.2%) than in the control group (28.7%) (OR 0.68, 95% CI [0.61 – 0.75], p<0.0001).
Comparing Beta Blockers in Heart Failure Patients
Multiple studies on patients with heart failure have shown that carvedilol is effective in reducing the risk of death and hospitalization from cardiovascular problems,10-13 and may be more beneficial in patients with complicated cardiovascular diseases when compared to other non-selective beta blockers.14 A study on patients (n=1,094) with chronic heart failure and EF ≤35% found that the risk of hospitalization for cardiovascular causes was reduced by 27% in the carvedilol group (14.1%) than in the placebo group (19.6%) (95% CI [2% – 45%], p=0.036).10 The combined risk of hospitalization or death was 38% lower in the carvedilol group (15.8%) than in the placebo group (24.6%) (95% CI [18% – 53%], p<0.001). A meta-analysis found that when compared against beta-1-selective blockers (e.g., atenolol, bisoprolol, metoprolol, and nebivolol), carvedilol significantly reduced all-cause mortality in systolic heart failure patients (8 trials, n=4,563) (risk ratio [RR] 0.85, 95% CI [0.78 – 0.93], p=0.0006).15 The large COMET study compared carvedilol and metoprolol treatment in patients with chronic heart failure (n=1,511).16 The study found that carvedilol extends survival, with an all-cause mortality lower in the carvedilol group (34%) when compared to the metoprolol group (40%) (hazard ratio [HR] 0.83, 95% CI [0.74 – 0.93], p=0.0017).
Beta Blockers for Coronary Artery Disease (CAD)
Although evidence for beta blocker use in patients with heart failure and left ventricular dysfunction is robust, evidence for its use in patients with CAD is less clear. Beta blocker use in patients with stable CAD is recommended by the 2012 ACC guidelines for stable ischemic heart disease as a first-line agent for symptom relief.6,7 A 1999 meta-analysis of 90 randomized trials comparing beta blockers, calcium antagonists, and nitrates on patients with stable angina concluded that beta blockers are associated with less adverse events than calcium antagonists and provide similar clinical benefits. Andersson et al.8 analyzed health records database of 26,793 patients who were discharged after the first cardiovascular event (acute coronary syndrome or coronary revascularization) and assessed whether beta blocker use was associated with outcomes. Patients with stable CAD experienced modest benefits. The study concluded that beta blocker use was associated with reduced risk of cardiac events only in patients with prior myocardial infarction. A 2012 longitudinal, observational study of 21,860 patients with known prior MI, known CAD without MI, and CAD risk factors only assessed the association of beta blocker use with cardiovascular events.9 The study found that rates of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for cardiovascular reasons were not significantly different between patients with beta blocker use and without beta blocker use.
Contraindications and Warnings
It is recommended that beta blockers should only be initiated in stable patients.3 The ACC/AHA 2017 guidelines for high blood pressure specify that beta blockers with intrinsic sympathomimetic activity such as acebutolol, penbutolol, and pindolol should be avoided in patients with ischemic heart disease or heart failure.4 Although it is safe for patients with ischemic heart disease or heart failure to use beta blockers such as atenolol, carvedilol, labetalol, metoprolol, and nebivolol, other heart diseases and conditions are listed as contraindications.17-26 Patients with one or more of the following heart conditions should avoid taking beta blockers:
- Second- or third-degree atrioventricular block
- Sick sinus syndrome or severe bradycardia of less than 45 to 50 beats per minute (unless a permanent pacemaker is in place)
- Cardiogenic shock or decompensated heart failure (New York Heart Association Class IV) that requires intravenous inotropic therapy
- Frishman WH. A historical perspective on the development of β-adrenergic blockers. Am J Hypertens. 2007;9(s4):19-27.
- Briasoulis A, Palla M, Afonso L. Meta-analysis of the effects of carvedilol versus metoprolol on all-cause mortality and hospitalizations in patients with heart failure. Am J Cardiol. 2015;115(8):1111-1115.
- Writing Committee M, 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(16):e240-327.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2017.
- Shibata MC, Flather MD, Wang D. Systematic review of the impact of beta blockers on mortality and hospital admissions in heart failure. Eur J Heart Fail. 2001;3(3):351-357.
- Steg PG, De Silva R. Beta-Blockers in Asymptomatic Coronary Artery Disease. No benefit or no evidence? 2014;64(3):253-255.
- Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. 2012;60(24):e44-e164.
- Andersson C, Shilane D, Go AS, et al. Beta-blocker therapy and cardiac events among patients with newly diagnosed coronary heart disease. JACC. 2014;64(3):247-252.
- Bangalore S, Steg G, Deedwania P, et al. beta-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA. 2012;308(13):1340-1349.
- Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334(21):1349-1355. 1996.
- Packer M, Coats AJS, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344(22):1651-1658.
- Packer M. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002;106(17):2194-2199.
- Fowler MB. Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Trial: carvedilol in severe heart failure. Am J Cardiol. 2004;93(9, Supplement 1):35-39.
- Chakraborty S, Shukla D, Mishra B, Singh S. Clinical updates on carvedilol: a first choice beta-blocker in the treatment of cardiovascular diseases. Expert Opin Drug Metab Toxicol. 2010;6(2):237-250.
- DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O'Keefe JH. Meta-analysis of carvedilol versus beta 1 selective beta-blockers (atenolol, bisoprolol, metoprolol, and nebivolol). Am J Cardiol. 2013;111(5):765-769.
- 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(9377):7-13.
- Carvedilol. In: Drugs and Lactation Database (LactMed). Bethesda (MD): National Library of Medicine (US); 2006.
- Auro-Carvedilol [package insert]. Ontario, CA: Aurobindo Pharma Inc.; 2013.
- Coreg [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- Coreg CR [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- American College of Cardiology. Carvedilol (Coreg) considerations for use. Carvedilol. American College of Cardiology. https://www.acc.org/tools-and-practice-support/clinical-toolkits/atrial-fibrillation-afib/rate-rhythm-dosing-table/carvedilol. Accessed September 10, 2018.
- Frishman WH. Carvedilol. N Engl J Med. 1998;339(24):1759-1765.
- Metoprolol succinate extended-release tablets [package insert]. Sodertalje, Sweden:AstraZeneca AB; 2006.
- Lopressor [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2008.
- Trandate [package insert]. Oakville, ON: Prometheus Laboratories Inc.; 2010.
- Bystolic [package insert]. St. Louis, MO: Forest Pharmaceuticals; 2011.