Journal of Cardiac Failure
Volume 16, Issue 9 , Pages 714-719 , September 2010

The Effects of Adenosine A1 Receptor Antagonism in Patients With Acute Decompensated Heart Failure and Worsening Renal Function: The REACH UP Study

  • Stephen S. Gottlieb, MD

      Affiliations

    • University of Maryland, Baltimore, MD
    • Corresponding Author InformationReprint requests: Stephen Gottlieb, MD, University of Maryland School of Medicine, 22 S. Greene St, Baltimore, MD 21209. Tel: (410) 328-8788; Fax: (410) 328-1048.
    • ,
  • Michael M. Givertz, MD

      Affiliations

    • Brigham and Women's Hospital, Boston, MA
    • ,
  • Marco Metra, MD

      Affiliations

    • University of Brescia, Brescia, Italy
    • ,
  • Kevin Gergich, MA

      Affiliations

    • Merck & Co., Inc, Whitehouse Station, NJ
    • ,
  • Steven Bird, MS

      Affiliations

    • Merck & Co., Inc, Whitehouse Station, NJ
    • ,
  • Charlotte Jones-Burton, MD, MS

      Affiliations

    • Merck & Co., Inc, Whitehouse Station, NJ
    • ,
  • Barry Massie, MD

      Affiliations

    • University of California, San Francisco
    • ,
  • Gad Cotter, MD

      Affiliations

    • Momentum Research, Durham, NC
    • ,
  • Piotr Ponikowski, MD

      Affiliations

    • Military Hospital, Department of Health Sciences, Medical University, Wroclaw, Poland
    • ,
  • Beth Weatherley, PhD

      Affiliations

    • Momentum Research, Durham, NC
    • ,
  • Christopher O'Connor, MD

      Affiliations

    • Duke University Medical Center, Durham, NC
    • ,
  • Howard Dittrich, MD

      Affiliations

    • NovaCardia, Inc, San Diego, CA

Received 11 February 2010 ,Revised 16 April 2010 ,Accepted 21 April 2010.

References 

  1. Gottlieb SS, Abraham W, Butler J, Forman DE, Loh E, Massie BM, et al. The prognostic importance of different definitions of worsening renal function in congestive heart failure. J Card Fail. 2002;8:136–141
  2. Forman DE, Butler J, Wang YF, Abraham WT, O'Connor CM, Gottlieb SS, et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol. 2004;43:61–67
  3. Metra M, Nodari S, Parrinello G, Bordonali T, Bugatti S, Danesi R, et al. Worsening renal function in patients hospitalised for acute heart failure: clinical implications and prognostic significance. Eur J Heart Fail. 2008;10:188–195
  4. Damman K, Navis G, Voors AA, Asselbergs FW, Smilde TDJ, Cleland JGF. Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail. 2007;13:599–608
  5. Dohadwala MM, Givertz MM. Role of adenosine antagonism in the cardiorenal syndrome. Cardiovasc Ther. 2008;26:276–286
  6. Gottlieb SS, Skettino SL, Wolff A, Beckman E, Fisher ML, Freudenberger R, et al. Effects of BG9719 (CVT-124), an A(1)-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure. J Am Coll Cardiol. 2000;35:56–59
  7. Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, et al. Effects of multiple oral doses of an a1 adenosine antagonist, bg9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study. J Am Coll Cardiol. 2007;50:600–606
  8. Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC. The effects of KW-3902, an adenosine A1-receptor antagonist, on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol. 2007;50:1551–1560
  9. Cotter G, Dittrich HC, Weatherley BD, Bloomfield DM, O'Connor CM, Metra M, et al. The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment. J Card Fail. 2008;14:631–640
  10. Metra M, Massie BM, O'Connor CM. Effects of rolofylline in patients with acute heart failure syndrome and renal impairment: findings from the placebo-controlled randomized study of the selective A1 adenosine receptor antagonist rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function (PROTECT) study. Eur Heart J. 2009;30:abstract 3584
  11. Dittrich HC, Gupta DK, Hack TC, Dowling T, Callahan J, Thomson S. The effect of KW-3902, an adenosine A1 receptor antagonist, on renal function and renal plasma flow in ambulatory patients with heart failure and renal impairment. J Card Fail. 2007;13:609–617
  12. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatine. Nephron. 1976;16:31–41
  13. Boison D. Adenosine and epilepsy: from therapeutic rationale to new therapeutic strategies. Neuroscientist. 2005;11:25–36
  14. de Silva R, Nikitin NP, Witte KKA, Rigby AS, Loh H, Nicholson A, et al. Effects of applying a standardised management algorithm for moderate to severe renal dysfunction in patients with chronic stable heart failure. Eur J Heart Fail. 2007;9:415–423
  15. Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol. 2009;3:589–596
  16. Mullens W, Abrahams Z, Skouri HN, Francis GS, Taylor DO, Starling RC, et al. Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function?. J Am Coll Cardiol. 2008;51:300–306

 Funded by NovaCardia, Inc. As of September 2007, NovaCardia is a wholly owned subsidiary of Merck & Co, Inc. Based on the lack of a benefit on the predefined end points in the PROTECT trial, Merck has reported it will not pursue further development of rolofylline.

 All decisions regarding this manuscript were made by a guest editor.

 See page 719 for disclosure information.

PII: S1071-9164(10)00196-X

doi: 10.1016/j.cardfail.2010.04.006

Journal of Cardiac Failure
Volume 16, Issue 9 , Pages 714-719 , September 2010

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