Journal Article

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

2011

Overview

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. 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. 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. 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). 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.

• Publisher: EM Inc USA,Elsevier,Elsevier Limited
• Subject: Aged / Arterial hypertension. Arterial hypotension / Biological and medical sciences / Biomarkers - blood / Blood and lymphatic vessels / Cardiology. Vascular system / Chronic Disease / chronic heart failure / Clinical trials / Delayed-Action Preparations / Diuretics - administration & dosage / Diuretics - adverse effects / Diuretics - therapeutic use / Drug therapy / Endpoint Determination / Female / Fibrosis - blood / Fibrosis - prevention & control / furosemide / Furosemide - administration & dosage / Furosemide - adverse effects / Furosemide - therapeutic use / Heart / Heart failure / Heart Failure - blood / Heart Failure - complications / Heart Failure - drug therapy / Heart Failure - pathology / Heart failure, cardiogenic pulmonary edema, cardiac enlargement / Humans / Hypertension / Hypertension - blood / Hypertension - complications / Hypertension - drug therapy / Hypertension - pathology / Internal Medicine / loop diuretics / Male / Medical sciences / myocardial fibrosis / Myocardium - metabolism / Myocardium - pathology / Peptide Fragments - blood / Pharmacology. Drug treatments / Procollagen - blood / procollagen type I carboxyterminal peptide / prolonged release / Prospective Studies / Quality of life / Sulfonamides - administration & dosage / Sulfonamides - adverse effects / Sulfonamides - therapeutic use / torasemide / Treatment Outcome