Therapeutic Research

Abstract

Objective：The efficacy of combination therapy of low−dose trichlormethiazide with conventional−dose furosemide in patients with refractory heart failure was assessed. Methods：Six patients with refractory heart failure and renal dysfunction（serum creatinine：1.7±0.8 mg／dL）under standard therapy received 40 mg furosemide daily for the first week, and additional trichlormethiazide 1 mg daily for the second week. Patients were monitored closely during hospitalization at least for these 2 weeks and then as outpatients for 6 months. Urine was collected for 24 hours during hospitalization to determine urinary volume, sodium excretion, creatinine clearance and fractional excretion of sodium. Blood laboratory examination, chest X−ray and echocardiographic measurements were performed before and 6 months after the combination therapy. Results：Combination of low−dose trichlormethiazide with conventional−dose furosemide significantly increased both urinary volume（1365±392 to 1875±402 mL／day, p＜0.05）and urinary sodium excretion（132±41 to 274±87 mmol／gCre, p＜0.01）, compared with the monotherapy of furosemide. Combination therapy also significantly enhanced fractional excretion of sodium from 1.7±0.9 to 3.7±2.5％（p＜0.05）compared with the monotherapy of furosemide, without significant changes of creatinine clearance（34±24 to 30±20mL／min）. After 6 months of combination therapy as outpatients, NYHA functional class（2.7±0.8 to 2.2±0.4, p＝0.08）and plasma BNP level（743±404 to 381±341 pg／mL, p＝0.06）tended to be improved, while clinically important hypokalemia, hyponatremia or hospitalization was not observed. Conclusions：Combination of low−dose trichlormethiazide with conventional−dose furosemide promotes natriuresis and improves conditions in patients with refractory heart failure and renal dysfunction.