Drug Development for Heart Failure With Preserved Ejection Fraction: What Pieces Are Missing From the Puzzle?

Published

Journal Article (Review)

Despite the growing number of patients with heart failure with preserved ejection fraction (HFpEF) and event rates comparable with many cancers, there remain no pharmacologic agents definitively proven to improve patient outcomes. Although phase II trials have intermittently yielded encouraging results, none have translated into successful achievement of a phase III primary end point. Thus, because of the urgent need to discover proven therapies, it is prudent to reevaluate our current approach to HFpEF drug development. In this review, we comment on key areas of uncertainty and importance relevant to successful drug discovery for HFpEF. These areas include the need to: clarify and homogenize the HFpEF definition; better understand the role of comorbidities and varying HFpEF etiology; use the heart failure hospitalization as the prime opportunity for trial enrollment; classify HFpEF patients within discrete clinicopathologic phenotypes for selected study; discover novel molecular drug targets; and determine predictors of specific causes of death to allow optimal matching of pharmacologic mechanisms with HFpEF subgroups most likely to benefit. Recognizing that the study of HFpEF is inherently challenging and complex, addressing these specific areas and overcoming their respective hurdles might maximize the chances of discovering a beneficial therapy.

Full Text

Duke Authors

Cited Authors

  • Senni, M; Greene, SJ; Butler, J; Fonarow, GC; Gheorghiade, M

Published Date

  • June 2017

Published In

Volume / Issue

  • 33 / 6

Start / End Page

  • 768 - 776

PubMed ID

  • 28545624

Pubmed Central ID

  • 28545624

Electronic International Standard Serial Number (EISSN)

  • 1916-7075

International Standard Serial Number (ISSN)

  • 0828-282X

Digital Object Identifier (DOI)

  • 10.1016/j.cjca.2017.03.013

Language

  • eng