A Prospective 1-year Comparison of Metoprolol and Carvedilol in Congestive Heart Failure - Metoprolol/Carvedilol


Metoprolol vs. carvedilol for mortality in moderate to severe heart failure.


To prospectively compare metoprolol and carvedilol in a heart failure population with moderate to severe symptoms despite triple therapy in a randomized, open label study, using clinical, symptom, and exercise endpoints, with antioxidant status as the primary endpoint.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 67
Mean Patient Age: 57
Female: 31
Mean Ejection Fraction: 19%

Patient Populations:

Moderate to severe symptoms of chronic left heart failure

Primary Endpoints:

Direct measurement of the antioxidant affects of carvedilol compared to metoprolol during one year of therapy as determined by thiobarbituric acid reactive substances and spectrophotometry.

Drug/Procedures Used:

Metoprolol, 6.25mg once a day for 1 week escalating in a weekly fashion to 25mg bid maintenance (50mg bid for patients >85kg); or carvedilol, 3.125mg bid for 1 week then up-titrated weekly to 25mg bid maintenance (50mg bid for patients >85kg).

Concomitant Medications:

Digoxin, diuretics, and (usually) an ACE inhibitor

Principal Findings:

The carvedilol (n=37) and metoprolol (n=30) groups were well-matched at baseline with no significant difference in percent of patients achieving target dose or in required alteration of diuretic dose during uptitration. Twenty participants did not complete the 12-month study, with these patients equally divided between the 2 groups.

Both groups demonstrated significant parallel clinical and exercise benefits over 1 year with no discernible difference between the two β-blockers in any of the measured parameters, including blood pressure, symptom score, QOL measures, clinical status, ejection fraction, or exercise parameters. Heart rate declined significantly with both drugs, but the decline with carvedilol (17 bpm) was greater than with metoprolol (10 bpm, p=0.05). This probably reflects the greater degree of beta blockade achieved with the relatively higher equivalent dose of carvedilol compared with metoprolol. TBARS, as a measure of antioxidant activity, declined significantly over time. This occurred as functional status improved, with no difference shown between the two groups.

As heart failure improved, dry weight tended to increase without any deterioration in renal function. This weight increase without edema may reflect an increase in mean muscle mass or beneficial effects of chronic β-blockade on cytokines and/or a reduction in oxidative stress.


Heart failure patients have been shown to have increased oxygen free radical production and/or a decreased ability to clear oxygen free radicals compared to age-matched controls. One assay to measure antioxidant activity uses thiobarbituric acid reactive substances (TBARS), which correlate with New York Heart Association functional class. (J Am Coll Cardiol 1997;29[suppl]:102A) Carvedilol and metoprolol demonstrated parallel clinical and exercise benefits over 12 months in this heart failure population, with no discernible difference between the two β-blockers in the measured parameters.


1. Circulation 1998;98(Suppl I):I-364. Preliminary results

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Statins, Acute Heart Failure, Stress

Keywords: Cytokines, Diuretics, Oxidative Stress, Blood Pressure, Edema, Propanolamines, Heart Rate, Vasodilator Agents, Carbazoles, Adrenergic alpha-1 Receptor Antagonists, Free Radicals, Heart Failure, Metoprolol, Thiobarbituric Acid Reactive Substances

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