Prospective, Randomized Comparison of Effect of Long-Term Treatment With Metoprolol or Carvedilol on Symptoms, Exercise, Ejection Fraction, and Oxidative Stress in Heart Failure

Abstract

Background-With ␤-blocker use becoming more prevalent in treating chronic heart failure (CHF), the choice of drugs raises important theoretical and practical questions. Although the second-generation compound metoprolol is ␤ 1 -selective, the third-generation compound carvedilol is ␤-nonselective, with ancillary pharmacological properties including ␣-blockade and antioxidant effects. A prospective comparison of these 2 agents can address the issue of optimal adrenergic blockade in selecting agents for therapy in CHF. Methods and Results-Sixty-seven patients with symptomatic stable heart failure were randomly assigned to receive either carvedilol or metoprolol in addition to standard therapy for CHF. Measured variables included symptoms, exercise, ejection fraction, and thiobarbituric acid-reactive substances (TBARS) as an indirect marker of free radical activity. Metoprolol and carvedilol were well tolerated, and both patient groups showed beneficial effects of ␤-blocker therapy in each of the measured parameters, with no between-group differences. Ejection fraction increased over 6 months from 18Ϯ6.3% to 23Ϯ8.7% (PϽ0.005) with metoprolol and from 19Ϯ8.5% to 25Ϯ9.9% (PϽ0.0005) with carvedilol (PϭNS between groups). With metoprolol, TBARS values decreased from 4.7Ϯ0.9 nmol/mL at baseline to 4.2Ϯ1.5 nmol/mL at month 4 to 3.9Ϯ1.0 nmol/mL at month 6 (PϽ0.0001). With carvedilol, there was a parallel decline from 4.7Ϯ1.4 to 4.2Ϯ1.3 to 4.1Ϯ1.2 nmol/mL over the same time frame (PϽ0.025), with no between-group difference in these changes. Conclusions-Carvedilol and metoprolol showed parallel beneficial effects in the measured parameters over 6 months, with no relevant between-group differences in this heart failure population. (Circulation. 1999;99:2645-2651.)

The Improvement Chest X-Ray After Carvedilol Theraphy in Heart Failure Due to Left to Right Shunt.

“…A direct interaction with free radical, such as superoxide and hydroxyl would neutralize those dangerous radical scavanger, as previously study by Kukin et al, 1999;Dandona et al, 2000;and Nakamura et al 2002. In this study, carvedilol has no significant difference in improving pulmonary vascularity. This was due to different degree of pulmonary hypertension in each subjects, depend on naturally history of pulmonary hypertension.…”

Carvedilol Decreases Elevated Oxidative Stress in Human Failing Myocardium

“…[12][13][14] Therefore, adrenergic receptor blockers are useful for catecholamine-induced oxidative stress. Actually, Kukin et al 16 reported that not only carvedilol but also metoprolol, a ␤ 1 -selective blocker, reduced plasma lipid peroxidation in patients with heart failure. Anti-ischemic properties, including negative chronotropic effects via ␤ receptor, may also be important, because ischemia has been shown to increase HNE formation in the heart.…”

“…12,13 Therefore, ␤-blocker therapy may prevent oxida-tive stress in patients with heart failure. Actually, Kukin et al 16 reported that ␤-blockers such as carvedilol and metoprolol reduced plasma thiobarbituric acid-reactive substances, a marker of lipid peroxidation, in patients with heart failure. Carvedilol is known not only as a vasodilating ␤-blocker but also as an antioxidant.…”

Which Beta-Blocker is Most Effective in Heart Failure?

“…Metra and coworkers reported a significantly greater increase in LV ejection fraction after 1 year treatment with carvedilol compared to metoprolol [37]. In contrast, Kukin et al found similar improvements in LV ejection fraction [38]. However, this was a smaller study over a shorter period.…”