title: Clinical trial strategies and future challenges in the investigation of human congestive heart failure.
abstract: Clinical research in the therapeutics of chronic congestive heart failure (CHF) has evolved from simple case reports and general-response studies in the 1960s to large, randomized, controlled trials conducted in the late 1980s and 1990s. Cumulatively, the investigations show that angiotensin-converting enzyme (ACE) inhibitors improve clinical status, exercise capacity, and survival; digoxin augments exercise capacity and, probably, clinical status, with unknown effects on survival; the vasodilator combination hydralazine-nitrate improves survival, and perhaps clinical status and exercise capacity; and the new vasodilator flosequinan has a favorable effect on clinical status and exercise capacity, but is associated with an increased risk of mortality at 100 mg/day (this agent has subsequently been withdrawn voluntarily by the manufacturer from clinical use). Advances in study design and methodology, combined with the outcomes of major clinical trials, have resulted in new challenges in the investigation of CHF in humans. To date, only the ACE inhibitors have been shown to affect all of the major CHF therapeutic end points in a positive manner. Is it reasonable to expect similar results from all future drug interventions? If not, which end points should be targeted? Must the survival end point be investigated for all CHF drugs under development? Can studies be performed ethically without background ACE inhibitor therapy? Have the optimum duration and methods for therapeutic trials in humans been determined? Should controlled trials of nonhemodynamic and nonneurohormonal interventions (e.g., anticoagulation, magnesium, exercise regimens) be performed? How can the results of clinical trials best be applied in treating the broad range of patients encountered in practice?(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Ohio State University College of Medicine, Columbus.
authors.forename: C V
authors.initials: CV
authors.lastname: Leier
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors