Clin Ther. 2011 Sep;33(9):1204-1213.e3. doi: 10.1016/j.clinthera.2011.08.006. Epub 2011 Sep 8.
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.
心肌中纤维胶原的合成和沉积的药物修饰可能会对心力衰竭（HF）患者的心脏功能、临床状况和预后产生影响。血清前胶原 I 型羧基端肽（PICP）是胶原 I 型纤维合成和心肌沉积的生化标志物。
本研究旨在评估持续释放（PR）型托拉塞米（torasemide-PR）和呋塞米对高血压合并慢性 HF 患者心肌纤维化的影响。
这是一项多中心、平行组、随机、开放标签、数据盲法评估的研究（PROBE：前瞻性随机开放标签终点研究）。患者被随机分为托拉塞米-PR（n = 77）或呋塞米（n = 78）治疗组，同时接受最佳慢性 HF 标准治疗。通过血清 PICP 水平评估托拉塞米-PR 和呋塞米对心肌纤维化的影响。28 例患者提前退出研究，每组 14 例。
共有 155 例患者被随机分组，其中 58.1%为男性。托拉塞米-PR 组患者的平均（标准差）年龄为 68.1（11.4）岁，呋塞米组为 69.3（9.8）岁。基线时，托拉塞米-PR 组 96.1%的患者和呋塞米组 89.7%的患者为 NYHA 心功能 II 级 HF。两组治疗患者的大多数均存在射血分数保留（EF >40%）。研究结束时，托拉塞米-PR 组和呋塞米组患者的血清 PICP 水平无差异（P = 0.75）。两组治疗基线浓度的调整差异（95%CI）为-1.2（-8.9 至 6.4）。
在患有轻度和临床稳定 HF 的高血压患者中，长期应用托拉塞米-PR 或呋塞米与血清 PICP 评估的心肌纤维化无显著相关性。临床试验注册号：NCT00409942。
