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New medical therapies for advanced left ventricular dysfunction
1Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
Insights
Current heart failure therapies are reviewed, with renin-angiotensin agents showing the most efficacy. Digoxin may benefit specific patients, while most calcium channel blockers are ineffective. Vesnarinone shows promise for improving mortality and symptoms.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Dilated cardiomyopathy and congestive heart failure treatments are evolving.
- Understanding therapeutic targets is crucial for current and future drug development.
Purpose of the Study:
- To analyze currently used therapeutic targets for heart failure.
- To evaluate the efficacy and potential benefits of various drug classes.
Main Methods:
- Review and analysis of existing therapeutic agents for heart failure.
- Assessment of drug effects on mortality, symptoms, and specific physiological pathways.
Main Results:
- Renin-angiotensin agents are the most efficacious.
- Digoxin may benefit specific patient groups; most calcium channel blockers are ineffective.
- Vesnarinone shows potential for improving mortality and symptoms, possibly due to anticytokine properties.
Conclusions:
- Therapeutic strategies for heart failure require careful consideration of drug class and individual patient factors.
- Newer agents and lower doses are under investigation, but evidence for some classes, like phosphodiesterase inhibitors, is limited for long-term use.
Abstract:
The analysis of currently used therapeutic targets provides considerable input in the choice of current and future therapies for dilated cardiomyopathy and congestive heart failure. Of the ion flux agents, a definitive answer concerning digoxin will soon be available. Currently, digoxin is likely of benefit to patients with persistent heart failure and significantly enlarged hearts despite therapy with preload and afterload reducing agents. Most currently available calcium channel blocking agents do not appear to be effective, although newer agents such as amlodipine and felodipine have yet to be adequately tested. Vesnarinone, which operates through the sodium and potassium rectifying channels and has limited phosphodiesterase inhibition, appears to provide a significant improvement in mortality and in symptoms. Part of the latter effect may be due to its anticytokine properties, which are currently being investigated. Analysis of vascular endothelial agents indicate that not all of the vasoactive agents improve survival, as demonstrated with prazosin and flosequinan. The dose of agents may be important, again demonstrating that less is better. Finally, those with additional effects, such as inositol triphosphate stimulation, may offer additional unique properties that may, in the future, provide benefit. Phosphodiesterase inhibitors are potentially beneficial in the short term but clearly should be avoided for long-term use. Lower doses of these agents are now being investigated, but the weight of evidence is against agents that operate primarily through phosphodiesterase inhibition. Renin angiotensin agents are the most efficacious of therapies available at this time. New angiotensin converting enzyme inhibitors are likely to add little to what is already known.(ABSTRACT TRUNCATED AT 250 WORDS)