title: 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.
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.
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023381:Endpoint Determination; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000517:prevention & control; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077786:Torsemide; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003692:Delayed-Action Preparations; D004232:Diuretics; D010446:Peptide Fragments; D011347:Procollagen; D013449:Sulfonamides; C042813:procollagen type I carboxy terminal peptide; D005665:Furosemide; D000077786:Torsemide