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Global Variations in Patient Populations and Outcomes in Heart Failure Clinical Trials

  • Clinical Trials (J Butler, Section Editor)
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Abstract

Purpose of Review

Heart failure is a global pandemic and there has been a growing effort to enroll patients from different geographical regions in randomized controlled trials. In this review, we examined regional variation in both patient characteristics and outcomes among several of the most recent global heart failure trials

Recent Findings

Retrospective analyses of global heart failure trials have identified marked variations in both baseline characteristics and management of heart failure by region of enrollment. In some trials, this variation has been significant enough to cause differential treatment effects.

Summary

We summarized key heterogeneity observed in global heart failure clinical trials. Differences in both patient population and organization of these trials abroad pose an important challenge in making interpretations and country-level decisions. As such, we encourage a concerted effort to account for these differences in future research.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Braunwald E. The war against heart failure: the Lancet lecture. Lancet (London, England). 2015;385:812–24.

    Article  Google Scholar 

  2. Callender T, Woodward M, Roth G, et al. Heart failure care in low- and middle-income countries: a systematic review and meta-analysis. PLoS Med. 2014;11:e1001699.

    Article  PubMed  PubMed Central  Google Scholar 

  3. •• Metra M, Mentz RJ, Hernandez AF, et al. Geographic Differences in Patients in a Global Acute Heart Failure Clinical Trial (from the ASCEND-HF Trial). Am J Cardiol. 2016;117:1771–8. Provided regional data on specific acute heart failure trial.

    Article  PubMed  Google Scholar 

  4. • Ferreira JP, Girerd N, Rossignol P, Zannad F. Geographic differences in heart failure trials. Eur J Heart Fail. 2015;17:893–905. Useful meta-analysis also looking at global heart failure trials in recent years.

    Article  PubMed  Google Scholar 

  5. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2014;370:1383–92.

    Article  CAS  PubMed  Google Scholar 

  6. •• Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015;131:34–42. Provided regional data on one of the major HFpEF trials in recent years.

    Article  CAS  PubMed  Google Scholar 

  7. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.

    Article  PubMed  Google Scholar 

  8. Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet (London, England). 2010;376:875–85.

    Article  CAS  Google Scholar 

  9. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.

    Article  CAS  PubMed  Google Scholar 

  10. •• Kristensen SL, Martinez F, Jhund PS, et al. Geographic variations in the PARADIGM-HF heart failure trial. Eur Heart J. 2016;37:3167–74. Provided regional data for comparison in recent ambulatory heart failure trial.

    Article  PubMed  PubMed Central  Google Scholar 

  11. O’Connor CM, Starling RC, Hernandez AF, et al. Effect of Nesiritide in Patients with Acute Decompensated Heart Failure. N Engl J Med. 2011;365:32–43.

    Article  PubMed  Google Scholar 

  12. Teerlink JR, Cotter G, Davison BA, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet (London, England). 2013;381:29–39.

    Article  CAS  Google Scholar 

  13. Gheorghiade M, Bohm M, Greene SJ, et al. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial. JAMA. 2013;309:1125–35.

    Article  CAS  PubMed  Google Scholar 

  14. • Mentz RJ, Cotter G, Cleland JG, et al. International differences in clinical characteristics, management, and outcomes in acute heart failure patients: better short-term outcomes in patients enrolled in Eastern Europe and Russia in the PROTECT trial. Eur J Heart Fail. 2014;16:614–24. Useful comparison of geographic differences in global heart failure trial.

    Article  PubMed  Google Scholar 

  15. Metra M, Ponikowski P, Cotter G, et al. Effects of serelaxin in subgroups of patients with acute heart failure: results from RELAX-AHF. Eur Heart J. 2013;34:3128–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. •• Greene SJ, Fonarow GC, Solomon SD, et al. Global variation in clinical profile, management, and post-discharge outcomes among patients hospitalized for worsening chronic heart failure: findings from the ASTRONAUT trial. Eur J Heart Fail. 2015;17:591–600. Provided regional data on acute heart failure trial.

    Article  PubMed  Google Scholar 

  17. • Pitt B, Gheorghiade M. Geographic variation in heart failure trials: time for scepticism? Eur J Heart Fail. 2014;16:601–2. Highlights potential drawbacks of globalization of heart failure trials.

    Article  PubMed  Google Scholar 

  18. Konstam MA, Gheorghiade M, Burnett Jr JC, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297:1319–31.

    Article  CAS  PubMed  Google Scholar 

  19. Blair JE, Zannad F, Konstam MA, et al. Continental differences in clinical characteristics, management, and outcomes in patients hospitalized with worsening heart failure results from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) program. J Am Coll Cardiol. 2008;52:1640–8.

    Article  PubMed  Google Scholar 

  20. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049–57.

    Article  CAS  PubMed  Google Scholar 

  21. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–9.

    Article  CAS  PubMed  Google Scholar 

  22. Greene SJ, Shah AN, Butler J, et al. Designing effective drug and device development programs for hospitalized heart failure: a proposal for pretrial registries. Am Heart J. 2014;168:142–9.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Chidiebube Egwim & Brittany Dixon

  2. Division of Cardiology, Duke University Medical Center, Durham, NC, USA

    Andrew P. Ambrosy & Robert J. Mentz

  3. Duke Clinical Research Institute, Durham, NC, USA

    Andrew P. Ambrosy & Robert J. Mentz

Authors
  1. Chidiebube Egwim
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  2. Brittany Dixon
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  3. Andrew P. Ambrosy
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  4. Robert J. Mentz
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Corresponding author

Correspondence to Robert J. Mentz.

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Conflict of Interest

Chidiebube Egwim, Brittany Dixon, and Andrew P. Ambrosy declare that they have no conflict of interest.

Robert J. Mentz has received grants from Novartis, Amgen, Otsuka, and Merck.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Clinical Trials

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Egwim, C., Dixon, B., Ambrosy, A.P. et al. Global Variations in Patient Populations and Outcomes in Heart Failure Clinical Trials. Curr Heart Fail Rep 14, 30–39 (2017). https://doi.org/10.1007/s11897-017-0316-1

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  • DOI: https://doi.org/10.1007/s11897-017-0316-1

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