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Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic
M R Bristow1, E M Gilbert, W T Abraham
1Division of Cardiology, University of Colorado HSC, Denver 80262, USA. michael.bristow@uchsc.edu
Insights
Carvedilol, a beta-blocker, improved left ventricular function and reduced mortality and hospitalization in patients with chronic heart failure. This study demonstrates carvedilol
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic heart failure (CHF) is a significant public health concern.
- Third-generation beta-blockers with vasodilator properties are being investigated for CHF treatment.
- Carvedilol's efficacy and safety in CHF require thorough evaluation.
Purpose of the Study:
- To establish the efficacy and safety of carvedilol in patients with chronic heart failure.
- To assess the dose-response relationship of carvedilol in mild to moderate CHF.
Main Methods:
- A multicenter, placebo-controlled trial involving 345 subjects with stable CHF.
- Randomization to placebo, low-dose (6.25 mg BID), medium-dose (12.5 mg BID), or high-dose (25 mg BID) carvedilol.
- Primary efficacy measured by 6-minute corridor walk test and 9-minute self-powered treadmill test over 6 months.
Main Results:
- Carvedilol showed no significant effect on submaximal exercise capacity.
- Dose-related improvements in left ventricular ejection fraction (EF) were observed.
- Significant dose-dependent reductions in all-cause mortality (73% combined) and hospitalization rates (58-64%) were noted.
Conclusions:
- Carvedilol demonstrated dose-related improvements in left ventricular function in patients with systolic dysfunction.
- Carvedilol significantly reduced mortality and hospitalization rates in mild to moderate heart failure.
- The drug was generally well-tolerated, supporting its use in CHF management.
Background:
We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" beta -blocking agent with vasodilator properties, in chronic heart failure.
Methods And Results:
Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P < .001 for linear dose response) and survival (respective crude mortality rates of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P < .001). When the three carvedilol groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects (P < .001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P = .01) and was generally well tolerated.
Conclusions:
In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.