There are two different forms of carvedilol: immediate-release tablets and extended-release capsules.1,2 Both forms of carvedilol were approved by the U.S. Food and Drug Administration (FDA) to treat patients with hypertension, mild-to-severe heart failure, or left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤40%) following myocardial infarction in clinically stable patients with or without symptoms of heart failure.
Heart Failure
In the 2013 guideline for the management of heart failure, the American College of Cardiology (ACC) and American Heart Association (AHA) recommended beta blockers, including carvedilol, for patients with Stage B and C heart failure with reduced ejection fraction (HFrEF).3 Stage B heart failure includes asymptomatic patients who have left ventricular hypertrophy and/or impaired left ventricular function.4 Stage C heart failure includes patients who have current or past heart failure symptoms associated with underlying structural heart disease. An update of the guideline in 2017 by the ACC, AHA, and the Heart Failure Society of America reiterated the 2013 recommendation.5
Multiple studies have shown that carvedilol is effective in reducing the risk of death and hospitalization in patients with heart failure.6-9 The US Carvedilol Heart Failure Study Group conducted a double-blinded, stratified study on patients with chronic heart failure and EF ≤35%.6 Patients received digoxin, diuretics, and angiotensin-converting enzyme inhibitors as background therapy, and were randomized to either the carvedilol or the placebo group. Carvedilol reduced the risk of mortality by 65% (95% confidence interval CI [39-80], p<0.001), finding an overall mortality rate of 3.2% and 7.8% for the carvedilol and the placebo group, respectively. The carvedilol group had a reduced risk of hospitalization for cardiovascular causes compared to the placebo group from 24.6% in the placebo group down to 15.8% for people taking carvedilol for a total of 27% (95% CI [3-45], p=0.036) reduction. Likewise, the carvedilol group had a reduced combined risk of hospitalization or death of 38% (95% CI [18-53], p<0.001) compared to the placebo group.
The Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) recruited patients with severe heart failure and an LVEF ≤25% and followed up for an average of 10.4 months.9 The study found that carvedilol reduced the risk of all-cause death by 35% (95% CI [19-48], p=0.0014). The mortality rate of the carvedilol group was 12.8% while that of the placebo group was 19.7%. Carvedilol also reduced the combined risk of death or hospitalization for any reason by 24%, the risk of death or hospitalization for cardiovascular causes by 27%, and the risk of death or hospitalization for heart failure by 31%. When compared to the placebo group, fewer patients randomized to the carvedilol group experienced hospitalizations due to heart failure (23.7% vs. 17.1%) or due to cardiovascular causes (27.7% vs. 21.3%).
Hypertension
Although carvedilol is a beta blocker with antihypertensive effects,1,2 beta blockers are not recommended as a first-line therapy for adults with hypertension according to the 2017 ACC/AHA hypertension guidelines.10 The guidelines do say that carvedilol is the preferred antihypertensive for patients with HFrEF.
Multiple studies have shown that carvedilol is effective in reducing systolic and diastolic blood pressure of patients with hypertension.11-18 A randomized, controlled trial studying patients with mild to moderate hypertension found that a month of treating patients with 25 mg carvedilol significantly decreased both systolic and diastolic pressure when compared to placebo (133.8 ± 9/86.6 ± 8.6 mm Hg vs 143.9 ± 8.9/94.4 ± 9.2 mm Hg, respectively, p<0.05).11 Similarly, a different study showed that a single 50 mg dose of carvedilol reduced systolic and diastolic blood pressure by 17.7% (p<0.01) and 15.4% (p<0.01), respectively, whereas the placebo group’s blood pressure remained unchanged.12
A study of older patients (n=22, average age 69 ± 8 years) with essential hypertension and left ventricular hypertrophy found antihypertensive benefits from 25 mg daily carvedilol treatment.17 After six months of treatment, the study found significant reductions in mean systolic blood pressure by 30 mm Hg (175 to 145 mm Hg, p<0.001) and diastolic blood pressure by 20 mm Hg (103 to 82 mm Hg, p<0.001) when compared to baseline. Diabetic patients with hypertension may also benefit from carvedilol. In 1997, another randomized, controlled trial19 of 45 non-insulin-dependent hypertensive diabetic patients found that carvedilol treatment significantly lowered systolic blood pressure by 13.1 ± 4.1 mm Hg (p<0.001) and diastolic blood pressure by 10.9 ± 3.5 mm Hg (p<0.001).
References
- Coreg [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- Coreg CR [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- 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.
- 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.
- Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161.
- 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.
- 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. J Am Coll Cardiol. 2018; 71 (19): e127-e248.
- Erdoðan O, Ertem B, Altun A. Comparison of antihypertensive efficacy of carvedilol and nebivolol in mild-to-moderate primary hypertension: a randomized trial. Anadolu Kardiyol Derg. 2011;11(4):310-313.
- Dupont AG, Van der Niepen P, Taeymans Y, et al. Effect of carvedilol on ambulatory blood pressure, renal hemodynamics, and cardiac function in essential hypertension. J Cardiovasc Pharmacol. 1987;10 Suppl 11:S130-136.
- McPhillips JJ, Schwemer GT, Scott DI, Zinny M, Patterson D. Effects of carvedilol on blood pressure in patients with mild to moderate hypertension. A dose response study. Drugs. 1988;36 Suppl 6:82-91.
- Morgan T, Snowden R, Butcher L. Effect of carvedilol and metoprolol on blood pressure, blood flow, and vascular resistance. J Cardiovasc Pharmacol. 1987;10 Suppl 11:S124-129.
- Franz IW, Agrawal B, Wiewel D, Ketelhut R. Comparison of the antihypertensive effects of carvedilol and metoprolol on resting and exercise blood pressure. Clin Investig. 1992;70 Suppl 1:S53-57.
- Moser M, Frishman W. Results of therapy with carvedilol, a beta-blocker vasodilator with antioxidant properties, in hypertensive patients. Am J Hypertens. 1998;11(1 Pt 2):15s-22s.
- Verza M, Ammendola S, Cambardella A, et al. Regression of left ventricular hypertrophy in hypertensive elderly patients with carvedilol. Arch Gerontol Geriatr. 1996;22 Suppl 1:143-147.
- Bakris GL, Iyengar M, Lukas MA, Ordronneau P, Weber MA. Effect of combining extended-release carvedilol and lisinopril in hypertension: results of the COSMOS study. J Clin Hypertens. 2010;12(9):678-686.
- 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(12):955-959.
