Acute carvedilol attenuated vasoconstriction to cold pressor test compared with metoprolol and placebo in normal subjects (3.1 vs 9.0 and 8.2 U, P<0.05), but chronic carvedilol did not in heart failure.
RCT
randomized
Does carvedilol limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol in normal subjects and patients with chronic heart failure?
Chronic administration of carvedilol does not attenuate vasoconstrictor responses to adrenergic stimuli compared to metoprolol in heart failure patients, suggesting its long-term benefits are not mediated by alpha-adrenergic blockade.
Absolute Event Rate: 3.1% vs 9%
p-value: p=<0.05
BACKGROUND: Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that alpha-adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol. METHODS AND RESULTS: Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip -3.5 U for carvedilol versus -1.2 U for metoprolol and -2.2 U for placebo, P=0.15; cold pressor test 3.1+/-8.9 U for carvedilol versus 9.0+/-2.7 U for metoprolol and 8.2+/-5.8 U for placebo, P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups. CONCLUSIONS: Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by alpha-adrenergic blockade.
Hryniewicz et al. (2003) conducted an RCT in Chronic heart failure and normal subjects. Carvedilol vs. Metoprolol (100 mg single dose or 200 mg daily) and placebo was evaluated on Forearm vascular resistance responses to cold pressor test in normal subjects (p=<0.05). Acute carvedilol attenuated vasoconstriction to cold pressor test compared with metoprolol and placebo in normal subjects (3.1 vs 9.0 and 8.2 U, P<0.05), but chronic carvedilol did not in heart failure.