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The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study

  • Clinical Trials (J. Butler, Section Editor)
  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Biomarker-guided management of patients with chronic heart failure with reduced ejection fraction (HFrEF) remains controversial.

Recent Findings

Biomarkers have established roles for diagnosis and prognostication in HF. Pilot data suggested that use of natriuretic peptides might be helpful to guide HF care. The recent Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) randomized–controlled trial did not find therapy guided by NT-proBNP to be more effective than usual care in improving the primary endpoint of HF hospitalization or cardiovascular mortality amongst patients with chronic HFrEF. Patients in GUIDE-IT received similar care and had similar NT-proBNP lowering regardless of treatment allocation.

Summary

Though biomarkers retain important standing for diagnosis and prognosis in HF, the GUIDE-IT trial results suggest carefully managed patients may not benefit from a biomarker-guided strategy. Future studies focusing this intervention on patients treated in a more real-world setting are needed.

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References

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

  1. •• Yancy CW, Jessup M, Bozkurt B, et al. ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure. J Am Coll Cardiol. 2017;70:776–803. Most recent update to the heart failure guidelines.

    Article  PubMed  Google Scholar 

  2. •• Januzzi JL, Troughton R. Are serial BNP measurements useful in heart failure management?: Serial natriuretic peptide measurements are useful in heart failure management. Circulation. 2013;127:500–8. Informative debate on biomarker-guided management.

    Article  PubMed  Google Scholar 

  3. •• Desai AS. Are serial BNP measurements useful in heart failure management?: Serial natriuretic peptide measurements are not useful in heart failure management: the art of medicine remains long. Circulation. 2013;127:509–16. Informative debate on biomarker-guided management.

    Article  PubMed  Google Scholar 

  4. Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freemantle N, Erdmann E, et al. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J. 2007;28:1592–7.

    Article  CAS  PubMed  Google Scholar 

  5. Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, et al. Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol. 2001;37:1228–33.

    Article  CAS  PubMed  Google Scholar 

  6. Frantz RP, Olson LJ, Grill D, Moualla SK, Nelson SM, Nobrega TP, et al. Carvedilol therapy is associated with a sustained decline in brain natriuretic peptide levels in patients with congestive heart failure. Am Heart J. 2005;149:541–7.

    Article  CAS  PubMed  Google Scholar 

  7. •• McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004. Landmark trial that brought neprilysin inhibition to the forefront of management of chronic systolic heart failure.

    Article  PubMed  Google Scholar 

  8. Januzzi JJL, Rehman SU, Mohammed AA, et al. Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction. J Am Coll Cardiol. 2011;58:1881–9.

    Article  CAS  PubMed  Google Scholar 

  9. Troughton RW, Frampton CM, Brunner-La Rocca H-P, et al. Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis. Eur Heart J. 2014;35:1559–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Weiner RB, Baggish AL, Chen-Tournoux A, Marshall JE, Gaggin HK, Bhardwaj A, et al. Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Eur J Heart Fail. 2013;15:342–51.

    Article  CAS  PubMed  Google Scholar 

  11. Gaggin HK, Truong QA, Rehman SU, Mohammed AA, Bhardwaj A, Parks KA, et al. Characterization and prediction of natriuretic peptide “nonresponse” during heart failure management: results from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) and the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) study. Congest Heart Fail. 2013;19:135–42.

    Article  PubMed  Google Scholar 

  12. Packer M, Poole-Wilson PA, Armstrong PW, Cleland JGF, Horowitz JD, Massie BM, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999;100:2312–8.

    Article  CAS  PubMed  Google Scholar 

  13. Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374:1840–8.

    Article  CAS  PubMed  Google Scholar 

  14. Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996;94:2807–16.

    Article  CAS  PubMed  Google Scholar 

  15. Fonarow GC, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, et al. Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the registry to improve the use of evidence-based heart failure therapies in the outpatient setting (IMPROVE HF). Circulation. 2010;122:585–96.

    Article  PubMed  Google Scholar 

  16. • Troughton RW, Frampton CM, Yandle TG, Espine EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet. 2000;355:1126–30. Sentinel trial of biomarker-guided management.

    Article  CAS  PubMed  Google Scholar 

  17. Berger R, Moertl D, Peter S, Ahmadi R, Huelsmann M, Yamuti S, et al. N-terminal pro-B-type natriuretic peptide-guided, intensive patient management in addition to multidisciplinary care in chronic heart failure: a 3-arm, prospective, randomized pilot study. J Am Coll Cardiol. 2010;55:645–53.

    Article  CAS  PubMed  Google Scholar 

  18. Jourdain P, Jondeau G, Funck F, Gueffet P, le Helloco A, Donal E, et al. Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP multicenter study. J Am Coll Cardiol. 2007;49:1733–9.

    Article  CAS  PubMed  Google Scholar 

  19. Lainchbury JG, Troughton RW, Strangman KM, Frampton CM, Pilbrow A, Yandle TG, et al. N-terminal pro-B-type natriuretic peptide-guided treatment for chronic heart failure: results from the BATTLESCARRED (NT-proBNP-assisted treatment to lessen serial cardiac readmissions and death) trial. J Am Coll Cardiol. 2009;55:53–60.

    Article  PubMed  Google Scholar 

  20. Pfisterer M, Buser P, Rickli H, Gutmann M, Erne P, Rickenbacher P, et al. BNP-guided vs symptom-guided heart failure therapy: the trial of intensified vs standard medical therapy in elderly patients with congestive heart failure (time-CHF) randomized trial. JAMA. 2009;301:383–92.

    Article  CAS  PubMed  Google Scholar 

  21. Eurlings LWM, van Pol PEJ, Kok WE, van Wijk S, Lodewijks-van der Bolt C, Balk AH, et al. Management of chronic heart failure guided by individual N-terminal pro-B-type natriuretic peptide targets: results of the PRIMA (can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. J Am Coll Cardiol. 2010;56:2090–100.

    Article  CAS  PubMed  Google Scholar 

  22. Shah MR, Califf RM, Nohria A, Bhapkar M, Bowers M, Mancini DM, et al. The STARBRITE trial: a randomized, pilot study of B-type natriuretic peptide-guided therapy in patients with advanced heart failure. J Card Fail. 2011;17:613–21.

    Article  PubMed  Google Scholar 

  23. Karlström P, Alehagen U, Boman K, Dahlström U, On behalf of the U-SG. Brain natriuretic peptide-guided treatment does not improve morbidity and mortality in extensively treated patients with chronic heart failure: responders to treatment have a significantly better outcome. Eur J Heart Fail. 2011;13:1096–103.

    Article  PubMed  Google Scholar 

  24. Pascual Figal D, Domingo M, Casas T, et al. Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients. Eur Heart J. 2008;29(8):1011–8.

    Article  CAS  PubMed  Google Scholar 

  25. Gandhi PU, Szymonifka J, Motiwala SR, Belcher AM, Januzzi JL Jr, Gaggin HK. Characterization and prediction of adverse events from intensive chronic heart failure management and effect on quality of life: results from the pro-B-type natriuretic peptide outpatient-tailored chronic heart failure therapy (PROTECT) study. J Card Fail. 2014;21:9–15.

    Article  PubMed  Google Scholar 

  26. Felker GM, Hasselblad V, Hernandez AF, O'Connor CM. Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials. Am Heart J. 2009;158:422–30.

    Article  CAS  PubMed  Google Scholar 

  27. Savarese G, Trimarco B, Dellegrottaglie S, Prastaro M, Gambardella F, Rengo G, et al. Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials. PLoS One. 2013;8:e58287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. •• Felker G, Anstrom KJ, Adams KF, et al. Effect of natriuretic peptide-guided therapy on hospitalization or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2017;318:713–20. The GUIDE-IT trial.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. •• Felker GM, Ahmad T, Anstrom KJ, et al. Rationale and Design of the GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study. JACC Heart Fail. 2014;2:457–65. The design of the GUIDE-IT trial.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Cleland JGF, McMurray JJV, Kjekshus J, Cornel JH, Dunselman P, Fonseca C, et al. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of Rosuvastatin: a report from CORONA (controlled Rosuvastatin multinational trial in heart failure). J Am Coll Cardiol. 2009;54:1850–9.

    Article  CAS  PubMed  Google Scholar 

  31. • Zile MR, Claggett BL, Prescott MF, et al. Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. J Am Coll Cardiol. 2016;68:2425–36. Study that demonstrates better outcomes with NT-proBNP <1000 ng/mL.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cardiology Division, Massachusetts General Hospital, 55 Fruit Street, GRB-800, Boston, MA, 02114, USA

    Nasrien E. Ibrahim & James L. Januzzi Jr

  2. Harvard Medical School, Boston, MA, USA

    Nasrien E. Ibrahim & James L. Januzzi Jr

  3. Baim Institute for Clinical Research, Boston, MA, USA

    James L. Januzzi Jr

Authors
  1. Nasrien E. Ibrahim
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  2. James L. Januzzi Jr
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Correspondence to Nasrien E. Ibrahim.

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Conflict of Interest

Nasrien E. Ibrahim declares no conflicts of interest.

James L. Januzzi reports grants and personal fees from Roche and Abbott during the conduct of the study.

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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Ibrahim, N.E., Januzzi, J.L. The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study. Curr Heart Fail Rep 15, 37–43 (2018). https://doi.org/10.1007/s11897-018-0381-0

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  • DOI: https://doi.org/10.1007/s11897-018-0381-0

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