Advertisement

Effects of Prolonged-Release Torasemide Versus Furosemide on Myocardial Fibrosis in Hypertensive Patients with Chronic Heart Failure: A Randomized, Blinded–End Point, Active-Controlled Study

  • The TORAFIC Investigators Group
    Author Footnotes
    ⁎ The TORAFIC Investigators are listed in the Acknowledgements.
  • Author Footnotes
    ⁎ The TORAFIC Investigators are listed in the Acknowledgements.
Published:September 09, 2011DOI:https://doi.org/10.1016/j.clinthera.2011.08.006

      Abstract

      Background

      The pharmacologic modification of the synthesis and deposition of fibrillar collagen in the myocardium may have effects on the cardiac function, clinical status, and prognosis of patients with heart failure (HF). Serum procollagen type I carboxyterminal peptide (PICP) is a biochemical marker of collagen type I fibers synthesis and myocardial deposition.

      Objective

      The aim of this study was to evaluate the effects of both the prolonged-release (PR) formulation of torasemide (torasemide-PR) and furosemide on myocardial fibrosis in hypertensive patients with chronic HF.

      Methods

      This was a multicenter, parallel-group, randomized, open-label study with blinded evaluation of data (PROBE: Prospective Randomized Open-label Blinded End points). Patients were randomly assigned to treatment with torasemide-PR (n = 77) or furosemide (n = 78), while receiving the best standard chronic HF treatment. Effects of torasemide-PR and furosemide on myocardial fibrosis were assessed through PICP serum levels. Twenty-eight patients discontinued prematurely from the study, 14 in each treatment group.

      Results

      One hundred fifty-five patients were randomized, 58.1% of whom were male. Mean (SD) age of the patients was 68.1 (11.4) years in the torasemide-PR group and 69.3 (9.8) years in the furosemide group. At baseline, 96.1% of patients in the torasemide-PR group and 89.7% in the furosemide group had NYHA class II HF. Most patients in both treatment groups presented with preserved ejection fraction (EF >40%). No differences were found in PICP serum levels at the end of the study between patients treated with torasemide-PR and patients treated with furosemide (P = 0.75). Adjusted difference (95% CI) for baseline concentration between both treatment groups was −1.2 (−8.9 to 6.4).

      Conclusions

      In hypertensive patients with mild and clinically stable HF, long-term administration of either torasemide-PR or furosemide was not associated with significant effects on myocardial fibrosis, as assessed by serum PICP. ClinicalTrials.gov identifier: NCT00409942.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Burlew B.S.
        • Weber K.T.
        Connective tissue and the heart.
        Cardiol Clin. 2000; 18: 435-442
        • Brower G.L.
        • Gardner J.D.
        • Forman M.F.
        • et al.
        The relationship between myocardial extracellular matrix remodeling and ventricular function.
        Eur J Cardiothorac Surg. 2006; 30: 604-610
        • Querejeta R.
        • Lopez B.
        • Gonzalez A.
        • et al.
        Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis.
        Circulation. 2004; 110: 1263-1268
        • Lopez B.
        • Gonzalez A.
        • Querejeta R.
        • Diez J.
        The use of collagen-derived serum peptides for the clinical assessment of hypertensive heart disease.
        J Hypertens. 2005; 23: 1445-1451
        • Querejeta R.
        • Varo N.
        • Lopez B.
        • et al.
        Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease.
        Circulation. 2000; 101: 1729-1735
        • Lopez B.
        • Gonzalez A.
        • Diez J.
        Circulating biomarkers of collagen metabolism in cardiac diseases.
        Circulation. 2010; 121: 1645-1654
        • Lopez B.
        • Querejeta R.
        • Gonzalez A.
        • et al.
        Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure.
        J Am Coll Cardiol. 2004; 43: 2028-2035
        • Veeraveedu P.T.
        • Watanabe K.
        • Ma M.
        • et al.
        Comparative effects of torasemide and furosemide in rats with heart failure.
        Biochem Pharmacol. 2008; 75: 649-659
        • Roca-Cusachs A.
        • Aracil-Vilar J.
        • Calvo-Gomez C.
        • et al.
        Clinical effects of torasemide prolonged release in mild-to-moderate hypertension: a randomized noninferiority trial versus torasemide immediate release.
        Cardiovas Ther. 2008; 26: 91-100
        • Díez A.
        • Coca A.
        • de Teresa E.
        • et al.
        • TORAFIC Investigators Group
        TORAFIC study protocol: torasemide prolonged release versus furosemide in patients with chronic heart failure.
        Expert Rev Cardiovasc Ther. 2009; 7: 897-904
        • Paulus W.J.
        • Tschope C.
        • Sanderson J.E.
        • et al.
        How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology.
        Eur Heart J. 2007; 28: 2539-2550
        • González A.
        • López B.
        • Querejeta R.
        • et al.
        Filling pressures and collagen metabolism in hypertensive patients with heart failure and normal ejection fraction.
        Hypertension. 2010; 55: 1418-1424
        • Rector T.S.
        • Cohn J.N.
        Assessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan.
        Am Heart J. 1992; 124: 1017-1025
        • Molenberghs G.
        • Kenward M.G.
        Missing Data in Clinical Studies.
        John Wiley & Sons, Chichester, UK2007
        • Senn S.
        Baseline and covariate information.
        in: Statistical Issues in Drug Development. John Wiley & Sons, Chichester, UK2007
        • Barbanoj M.J.
        • Ballester M.R.
        • Antonijoan R.M.
        • et al.
        A bioavailability/bioequivalence and pharmacokinetic study of two oral doses of torasemide (5 and 10 mg): prolonged-release versus the conventional formulation.
        Clin Exp Pharmacol Physiol. 2009; 36: 469-477