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A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: Dose

Although the long-term use of carvedilol may result in tolerance to its a-blockade properties analogous to that produced by prazosin, this does not seem to affect its beneficial long-term effects as shown by Packer et al in their 1996 report on the effect of carvedilol on 1,094 patients with mixed ischemic and idiopathic DCM with mild, moderate, and severe CHF. The Data and Safety Monitoring Board recommended termination of that study because the mortality over 12 months was 7.8% in the placebo group and 3.2% in the carvedilol group, a 59% reduction. There was also a 27% reduction in risk of hospitalization for cardiovascular causes.
Not yet available in the United States is nebivolol, a novel β-blocker that can improve left ventricular contractile function. In a South African 3-month placebo-controlled trial in 24 patients, most of whom had idiopathic DCM, the ejection fraction and stroke volume increased with a fall in end-diastolic pressure as well as mass and end-diastolic and systolic volumes.
In 1993, Waagstein et al10 suggested starting with 5 mg of metoprolol twice daily for 2 to 7 days. If that is tolerated, then gradually increase the dose up to as much as 150 mg/d as a rule, and rarely up to 200 mg/d. Engelmeier et al7 claim that you can go as high as 200 mg/d if you increase the dose slowly enough. If the CHF is very severe, a starting dose of 2.5 mg/d for a few days is safer than 5 mg. mycanadianpharmacy

Nonselective agents such as timolol and propranolol consistently have resulted in a significant fall in the incidence of sudden death after infarction. Since it is difficult to show that low or moderate doses of Pi-selective agents decrease the incidence of sudden death, perhaps the 30 to 40% of P2-receptors should also be blocked by nonselective p-blockers not only after infarction but also for CHF. At first sight it may not be considered valid to extrapolate postinfarction trials to the effects of P-blockers in CHF. It could be argued that the high doses of metoprolol in the postinfarction studies were successful because the patients who escaped sudden death were accidently selected out because they may have had high levels of sympathetic activity. However, this would make the extrapolation to CHF more logical because CHF patients may have even higher sympathetic activation than most postinfarction patients. One may therefore speculate that after a few months when maximum doses of β1-selective agents such as metoprolol have been achieved, perhaps there are patients with such a high level of sympathetic activation that they then require either a nonselective β-blocker or an increase in the dose of the β1-selective blocker so that it also acts as a β2-blocker. This concept, although not supported by any studies, is suggested by the surprising beneficial results with carvedilol.

Category: Heart Failure

Tags: ACE inhibitors, bucindolol, carvedilol, congestive heart failure, metoprolol, upregulation