ABSTRACT
During the last 10 years, treatment for symptom relief and hemodynamic improvement in congestive heart failure increasingly has been evaluated long-term not only for safety, but also for efficacy in reducing mortality rate and associated hospitalization rate (‘‘major morbidity’’). Some treatments have shown sufficient effectiveness in improving natural history in congestive heart failure populations that they have been given regulatory approval for prophylaxis as well as for therapeutic use. These agents are labeled for prophylaxis and it is possible to advertise them for this purpose. The effect of these approvals has been salutary in providing guidance, particularly for prescribers who have not had the opportunity to assess the voluminous relevant data in order to draw firm conclusions about appropriate therapy. But, to an increasing extent, such approval has been interpreted as part of a mandate for the routine prophylactic use of these drugs. In addition, at a time when managed care increasingly is becoming a factor in management decisions, patterns of treatment increasingly are being codified, with legal and economic implications for doctors who do not abide by practices defined by third parties. The FDA did not cause this situation, but it has to deal with the results. Together with sponsors, regulators must attempt to resolve a problem that has resulted unintentionally from approval of drugs that beneficially alter natural history of CHF: preventing development of other, potentially better agents, which manifest
potentially deleterious interactions with approved drugs. This is a problem of considerable magnitude. For example, drugs that have been approved for prophylactic use to reduce the rate of development of natural history of endpoints include several angiotensin converting enzyme inhibitors and the alpha-and beta-blocker carvedilol. In addition, though not yet approved by the FDA, drugs reported to improve natural history include vasodilators that are non-ACE inhibitors, some beta-blockers, and some positive inotropic agents or agents of unknown mechanism. Included in this last category is vesnarinone, even though its range of efficacy is unclear. In addition, of course, digitalis and diuretics are approved for symptom relief and can be additive in their effects with other agents for this purpose.
