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Present and future pharmacotherapy for heart failure
Sheila A Doggrell1, Lindsay Brown
1Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, QLD 4072, Australia. s.doggrell@mailbox.uq.edu.au
Insights
Optimizing heart failure (HF) pharmacotherapy involves adjusting angiotensin-converting enzyme inhibitor (ACEI) doses and considering angiotensin receptor-1 antagonists. Beta-blockers like carvedilol and specific digitalis use are key for mortality reduction and inotropic support in HF patients.
Area of Science:
- Cardiology
- Pharmacology
- Internal Medicine
Background:
- Current heart failure (HF) pharmacotherapy guidelines recommend diuretics, ACE inhibitors (ACEIs), beta-blockers, and digitalis.
- Optimizing ACEI dosage, such as lisinopril, can enhance therapeutic benefits in HF.
- Selective angiotensin receptor-1 (AT(1)) antagonists offer an alternative for patients intolerant to ACEIs and may provide cumulative benefits when used concurrently.
Purpose of the Study:
- To review current and emerging pharmacotherapies for heart failure (HF).
- To evaluate the efficacy and optimal use of various drug classes in HF management.
- To identify potential novel treatments for decompensated and chronic HF.
Main Methods:
- Review of current American College of Cardiology and American Heart Association guidelines for HF pharmacotherapy.
- Analysis of clinical trial data on ACE inhibitors, AT(1) antagonists, beta-blockers, digitalis, and newer agents.
- Evaluation of evidence for drugs like spironolactone, carvedilol, levosimendan, amiodarone, and nesiritide in different HF stages and conditions.
Main Results:
- Optimizing ACEI dose (e.g., lisinopril) improves HF outcomes.
- AT(1) antagonists are effective alternatives and potential adjuncts to ACEIs.
- Specific beta-blockers (carvedilol, metoprolol, bisoprolol) reduce mortality in severe HF; others like celiprolol and bucindolol do not.
- Spironolactone shows benefit in advanced HF and warrants study in less severe HF and with beta-blockers.
- Digitalis provides inotropic support without mortality benefit; phosphodiesterase inhibitors are associated with increased mortality.
- Levosimendan may aid hospital treatment of decompensated HF; amiodarone is considered for high-risk arrhythmias, potentially superseded by implantable cardioverter defibrillators.
- Nesiritide is available for decompensated HF; vasopeptidase inhibitors and endothelin-A receptor antagonists require further investigation.
- Etanercept showed no benefit in a large trial; recombinant growth hormone yielded variable results.
Conclusions:
- Current HF pharmacotherapy can be optimized through precise drug selection and dosage adjustments.
- Evidence supports the use of specific ACEIs, AT(1) antagonists, and beta-blockers for improving HF outcomes and reducing mortality.
- Further research is needed for novel agents, while some existing therapies like digitalis remain crucial for specific effects despite not impacting mortality.
Abstract:
The pharmacotherapy currently recommended by the American College of Cardiology and the American Heart Association for heart failure (HF) is a diuretic, an angiotensin-converting enzyme inhibitor (ACEI), a beta-adrenoceptor antagonist and (usually) digitalis. This current treatment of HF may be improved by optimising the dose of ACEI used, as increasing the dose of lisinopril increases its benefits in HF. Selective angiotensin receptor-1 (AT(1)) antagonists are effective alternatives for those who cannot tolerate ACEIs. AT(1) antagonists may also be used in combination with ACEIs, as some studies have shown cumulative benefits for the combination. In addition to being used in Stage IV HF patients, in whom it has a marked benefit, spironolactone should be studied in less severe HF and in the presence of beta-blockers. The use of carvedilol, extended-release metoprolol and bisoprolol should be extended to severe HF patients as these agents have been shown to decrease mortality in this group. The ancillary properties of carvedilol, particularly antagonism at prejunctional beta -adrenoceptors, may give it additional benefits to selective beta(1)-adrenoceptor antagonists. Celiprolol and bucindolol are not the beta-blockers of choice in HF, as they do not decrease mortality. Although digitalis does not reduce mortality, it remains the only option for a long-term positive inotropic effect, as the long-term use of the phosphodiesterase inhibitors is associated with increased mortality. The calcium sensitising drug levosimendan may be useful in the hospital treatment of decompensated HF to increase cardiac output and improve dyspnoea and fatigue. The antiarrhythmic drug amiodarone should probably be used in patients at high risk of arrhythmic or sudden death, although this treatment may soon be superseded by the more expensive implanted cardioverter defibrillators, which are probably more effective and have fewer side effects. The natriuretic peptide nesiritide has recently been introduced for the hospital treatment of decompensated HF. Novel drugs that may be beneficial in the treatment of HF include the vasopeptidase inhibitors and the selective endothelin-A receptor antagonists but these require much more investigation. However, disappointing results have been obtained in a large clinical trial of the tumour necrosis factor alpha antagonist etanercept, where no likelihood of a difference between placebo and etanercept was observed. Small clinical trials with recombinant growth hormone to thicken ventricles in dilated cardiomyopathy have given variable results.