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Clinical trials in hospitalized heart failure patients: targeting interventions to optimal phenotypic subpopulations

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Abstract

With one possible exception, the last decade of clinical trials in hospitalized heart failure (HHF) patients has failed to demonstrate improvement in long-term clinical outcomes. This trend necessitates a need to evaluate optimal drug development strategies and standards of trial conduct. It has become increasingly important to recognize the heterogeneity among HHF patients and the differential characterization of novel drug candidates. Targeting these agents to specific subpopulations may afford optimal net response related to the particular mode of action of the drug. Analyses of previous trials demonstrate profound differences in the baseline characteristics of patients enrolled across global regions and participating sites. Such differences may influence risks for events and interpretation of results. Therefore, the actual execution of trials and the epidemiology of HHF populations at the investigative sites must be taken into consideration. Collaboration among participating sites including the provision of registry data tailored to the planned development program will optimize trial conduct. Observational data prior to study initiation may enable sites to feedback and engage in protocol development to allow for feasible and valid clinical trial conduct. This site-centered, epidemiology-based network environment may facilitate studies in specific patient populations and promote optimal data collection and clear interpretation of drug safety and efficacy. This review summarizes the roundtable discussion held by a multidisciplinary team of representatives from academia, National Institutes of Health, industry, regulatory agencies, payers, and contract and academic research organizations to answer the question: Who should be targeted for novel therapies in HHF?

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Acknowledgments

None.

Conflict of interest

Javed Butler: Research Support: National Institutes of Health, European Union, Health Resource Services Administration, Food and Drug Administration; Consultant: Amgen, Bayer, Celladon, Gambro, GE Healthcare, Janssen, Medtronic, Novartis, Ono, Relypsa, Trevena; Stock Options: Stemedica. Lothar Roessig: Employee of Bayer Pharma AG. Gregg C Fonarow: Research support: Agency for Healthcare Research and Quality (significant), Consultant: Medtronic (modest), Gambro (significant), and Novartis (significant). Marco Metra: Received honoraria from Bayer, Corthera, Novartis, and Servier for speeches or participation in advisory boards/steering committees. Gadi Cotter: Employee of Momentum-Research, Inc. Stuart Kupfer: Employee of Takeda Global Research and Development Center, Inc. Andrew Zalewski: Employee of Novartis Pharmaceutical Corporation. Naoki Sato: Consultant to Chugai Pharmaceutical Company and honoraria from Daiichi-Sankyo, Otsuka, Philips Respironics, Astellas, Ono, Eisai, Chugai, Mitsubishi-Tanabe, Sanofi-Aventis, and Novartis pharmaceuticals. Mihai Gheorghiade: Consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical and Trevena Therapeutics. Muthiah Vaduganathan, Stephen J Greene, and Gerasimos Filippatos have no conflicts of interest or financial ties to disclose.

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Authors and Affiliations

  1. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Muthiah Vaduganathan

  2. Cardiology Division, Emory University Hospital, Atlanta, GA, USA

    Javed Butler

  3. Novartis Pharmaceutical Corporation, East Hanover, NJ, USA

    Lothar Roessig

  4. Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan-UCLA Medical Center, Los Angeles, CA, USA

    Gregg C. Fonarow

  5. Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 201 East Huron Street, Galter 3-150, Chicago, IL, 60611, USA

    Stephen J. Greene & Mihai Gheorghiade

  6. Division of Cardiology, University of Brescia, Brescia, Italy

    Marco Metra

  7. Momentum-Research, Inc., Durham, NC, USA

    Gadi Cotter

  8. Takeda Global Research and Development Center, Inc., Deerfield, IL, USA

    Stuart Kupfer

  9. Bayer Pharma AG, Berlin, Germany

    Andrew Zalewski

  10. Department of Internal Medicine and Cardiology, Nippon Medical School Musashi-Kosugi Hospital, Kanagawa, Japan

    Naoki Sato

  11. Attikon University Hospital, Athens, Greece

    Gerasimos Filippatos

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  1. Muthiah Vaduganathan
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  2. Javed Butler
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  4. Gregg C. Fonarow
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  7. Gadi Cotter
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  10. Naoki Sato
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  11. Gerasimos Filippatos
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Correspondence to Mihai Gheorghiade.

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Vaduganathan, M., Butler, J., Roessig, L. et al. Clinical trials in hospitalized heart failure patients: targeting interventions to optimal phenotypic subpopulations. Heart Fail Rev 20, 393–400 (2015). https://doi.org/10.1007/s10741-015-9485-8

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  • DOI: https://doi.org/10.1007/s10741-015-9485-8

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