Clinical development of pharmacologic agents for acute heart failure syndromes

A proposal for a mechanistic translational phase

Mihai Gheorghiade, Peter Pang, Christopher M. O'Connor, Krishna Prasad, John McMurray, John R. Teerlink, Mona Fiuzat, Hani Sabbah, Michel Komajda

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Hospitalization for acute heart failure syndromes (AHFS) predicts a poor prognosis, with postdischarge mortality and rehospitalization rates reaching 45% within 60 to 90 days. Despite the use of evidence-based therapies and adherence to national process measures, these event rates have largely remained the same over the past decade. Given the current and growing burden of AHFS, there exists a substantial unmet need for novel therapies that improve outcomes. However, attempts to improve symptoms and/or reduce postdischarge events have failed to produce positive results, either because of safety and/or efficacy. These negative results may be related to the drug itself, the protocol in terms of patient selection and/or end points, and/or the trial execution. Although experts may not agree on the exact reasons to explain the lack of success to date of phase III trials in AHFS, there is agreement that clinical benefits observed in phase II trials were not reproduced in phase III trials. A different approach may be needed. In November of 2009, a meeting was held at the Food and Drug Administration with the primary purpose of identifying the reasons why benefits observed during phase II did not translate into benefits in phase III to improve future trial design. Although multiple domains of trial design were discussed, the participants identified a lack of in-depth understanding of novel molecules before pivotal trials in AHFS as a possible contributor to the disappointing results of recent large trials. In this brief report, we outline the T1 or translational phase of research for AHFS clinical development as an important first step toward greater success in AHFS clinical trials.

Original languageEnglish (US)
Pages (from-to)224-232
Number of pages9
JournalAmerican Heart Journal
Volume161
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

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Heart Failure
Process Assessment (Health Care)
Translational Medical Research
United States Food and Drug Administration
Patient Selection
Hospitalization
Clinical Trials
Safety
Mortality
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Clinical development of pharmacologic agents for acute heart failure syndromes : A proposal for a mechanistic translational phase. / Gheorghiade, Mihai; Pang, Peter; O'Connor, Christopher M.; Prasad, Krishna; McMurray, John; Teerlink, John R.; Fiuzat, Mona; Sabbah, Hani; Komajda, Michel.

In: American Heart Journal, Vol. 161, No. 2, 02.2011, p. 224-232.

Research output: Contribution to journalArticle

Gheorghiade, M, Pang, P, O'Connor, CM, Prasad, K, McMurray, J, Teerlink, JR, Fiuzat, M, Sabbah, H & Komajda, M 2011, 'Clinical development of pharmacologic agents for acute heart failure syndromes: A proposal for a mechanistic translational phase', American Heart Journal, vol. 161, no. 2, pp. 224-232. https://doi.org/10.1016/j.ahj.2010.10.023
Gheorghiade, Mihai ; Pang, Peter ; O'Connor, Christopher M. ; Prasad, Krishna ; McMurray, John ; Teerlink, John R. ; Fiuzat, Mona ; Sabbah, Hani ; Komajda, Michel. / Clinical development of pharmacologic agents for acute heart failure syndromes : A proposal for a mechanistic translational phase. In: American Heart Journal. 2011 ; Vol. 161, No. 2. pp. 224-232.
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