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Clinical development of pharmacologic agents for acute heart failure syndromes: a proposal for a mechanistic translational phase.

Publication ,  Journal Article
Gheorghiade, M; Pang, PS; O'Connor, CM; Prasad, K; McMurray, J; Teerlink, JR; Fiuzat, M; Sabbah, H; Komajda, M
Published in: Am Heart J
February 2011

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.

Duke Scholars

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2011

Volume

161

Issue

2

Start / End Page

224 / 232

Location

United States

Related Subject Headings

  • Translational Research, Biomedical
  • Syndrome
  • Humans
  • Heart Failure
  • Clinical Trials as Topic
  • Cardiovascular System & Hematology
  • Acute Disease
  • 3201 Cardiovascular medicine and haematology
  • 1117 Public Health and Health Services
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gheorghiade, M., Pang, P. S., O’Connor, C. M., Prasad, K., McMurray, J., Teerlink, J. R., … Komajda, M. (2011). Clinical development of pharmacologic agents for acute heart failure syndromes: a proposal for a mechanistic translational phase. Am Heart J, 161(2), 224–232. https://doi.org/10.1016/j.ahj.2010.10.023
Gheorghiade, Mihai, Peter S. Pang, Christopher M. O’Connor, Krishna Prasad, John McMurray, John R. Teerlink, Mona Fiuzat, Hani Sabbah, and Michel Komajda. “Clinical development of pharmacologic agents for acute heart failure syndromes: a proposal for a mechanistic translational phase.Am Heart J 161, no. 2 (February 2011): 224–32. https://doi.org/10.1016/j.ahj.2010.10.023.
Gheorghiade M, Pang PS, O’Connor CM, Prasad K, McMurray J, Teerlink JR, et al. Clinical development of pharmacologic agents for acute heart failure syndromes: a proposal for a mechanistic translational phase. Am Heart J. 2011 Feb;161(2):224–32.
Gheorghiade, Mihai, et al. “Clinical development of pharmacologic agents for acute heart failure syndromes: a proposal for a mechanistic translational phase.Am Heart J, vol. 161, no. 2, Feb. 2011, pp. 224–32. Pubmed, doi:10.1016/j.ahj.2010.10.023.
Gheorghiade M, Pang PS, O’Connor CM, Prasad K, McMurray J, Teerlink JR, Fiuzat M, Sabbah H, Komajda M. Clinical development of pharmacologic agents for acute heart failure syndromes: a proposal for a mechanistic translational phase. Am Heart J. 2011 Feb;161(2):224–232.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2011

Volume

161

Issue

2

Start / End Page

224 / 232

Location

United States

Related Subject Headings

  • Translational Research, Biomedical
  • Syndrome
  • Humans
  • Heart Failure
  • Clinical Trials as Topic
  • Cardiovascular System & Hematology
  • Acute Disease
  • 3201 Cardiovascular medicine and haematology
  • 1117 Public Health and Health Services
  • 1102 Cardiorespiratory Medicine and Haematology