Improving clinical outcomes with drug treatment in heart failure: what have trials taught?
Pharmacologic clinical trials in heart failure (HF) have provided substantial advances in effective treatment of this condition, moving us from our focus on short-term symptom relief to an expectation of substantial improvement in long-term clinical outcomes for our patients. Based on an appreciation of the importance of neurohormonal activation in the pathophysiology of HF, clinical trials have demonstrated the value of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in impeding the progression of HF and in reducing morbidity and mortality for patients with this condition. Clinical trials have further demonstrated the benefits of digoxin in improving symptoms and reducing hospitalization frequency, as well as in aldosterone blockade, at least in patients with severe symptoms. Given the ethical imperative to treat with ACE inhibitors, the angiotensin receptor antagonists have been difficult to study; nevertheless, their value is becoming increasingly clear, particularly for patients intolerant of ACE inhibitors. Trials with several classes of newer agents-cytokine antagonists, endothelin receptor blockers, and vasopeptidase inhibitors-have recently yielded disappointing results. Early results with vasopressin receptor antagonists provide some promise of long-term benefit. Clinical trials have provided significant treatment advances; ongoing and future trials will demonstrate the degree to which we can improve on what we have achieved to date with pharmacologic treatments.
Konstam
Marvin A
MA
Department of Medicine, Division of Cardiology, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA. MKonstam@Lifespan.org
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000450:Aldosterone / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D065092:Antidiuretic Hormone Receptor Antagonists; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors; D004077:Digoxin / Q000627:therapeutic use; D018450:Disease Progression; D015507:Drugs, Investigational / Q000627:therapeutic use; D065128:Endothelin Receptor Antagonists; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D012306:Risk; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D016207:Cytokines; D015507:Drugs, Investigational; D065128:Endothelin Receptor Antagonists; D000450:Aldosterone; D004077:Digoxin