Present and future pharmacotherapy for heart failure.
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should probably be used in patients at high risk of arrhythmic or sudden death, although this treatment may soon be superseded by the more expensive implanted cardioverter defibrillators, which are probably more effective and have fewer side effects.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.
Doggrell
Sheila A
SA
Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, QLD 4072, Australia. s.doggrell@mailbox.uq.edu.au
Brown
Lindsay
L
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D065092:Antidiuretic Hormone Receptor Antagonists; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D016232:Endothelins / Q000037:antagonists & inhibitors; D006333:Heart Failure / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D002316:Cardiotonic Agents; D004232:Diuretics; D016232:Endothelins; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D019382:Human Growth Hormone; D009320:Atrial Natriuretic Factor