Efficacy & Safety of Torsemide & Spironolactone FDC in HF Patients: Insights from RESTORE HF Study
Introduction
The burden of heart failure (HF) is increasing in India. This increase has been attributed to the increasing prevalence of various risk factors including coronary artery disease (CAD), hypertension, and diabetes. Optimal volume management has a pivotal role for achieving symptom relief and for the prevention of acute decompensation in HF patients. Torsemide, a potent loop diuretic promotes diuresis and alleviates the volume overload in these patients. Spironolactone, a mineralocorticoid receptor antagonist has demonstrated significant reduction in mortality and hospitalization in patients with severe HF. Currently there is dearth of data on the efficacy and safety of a fixed dose combination (FDC) of torsemide and spironolactone.
Aim
The RESTORE-HF (Real-world Effectiveness and Safety of Torsemide and Spironolactone FDC in Indian Heart Failure Patients) study ascertained the real-world effectiveness and safety of torsemide-spironolactone FDC in HF patients in India.
Patient Profile
- Patients aged 18–75 years with HF with reduced ejection fraction (HFrEF; EF ≤40%) and elevated N-terminal pro–B-type natriuretic peptide levels (NTproBNP; >450 pg/mL for age <50 years and >900 pg/mL for age 50–75 years).
- The study participants had a New York Heart Association (NYHA) Class II or III.
- Patients with NYHA class II had at least one of the objective signs of fluid retention, such as pedal edema, elevated jugular venous pressure, basal rales, dilated plethoric inferior vena cava on ultrasound, or evidence of lung congestion on chest X-ray.
Methods
Study Design
- A prospective, multicentre, observational study, conducted across 101 centres in India.
Treatment Strategy
- The study participants were initiated on an FDC of torsemide and spironolactone (10/25 mg or 10/50 mg).
- Participants were followed over 3 weeks from baseline.
Outcomes
Primary Outcome
- The change in body weight
Secondary Outcomes
- Changes in NYHA functional class, changes in edema grade, occurrence of adverse events (AEs), and physician and patient assessments of efficacy and tolerability.
Results
- Overall, 1841 patients were screened and 1752 of them were enrolled. A total of 1520 participants completed the study. The mean age of the study participants was 58.49 years, 61.36% of them were male. The mean body weight for the study population was 75.44 kg.
- There was a significant reduction of 2.41 kg in mean body weight from baseline to 3 weeks (75.54 kg to 73.13 kg; p < 0.0001) (Fig. 1).
Fig. 1: Change in body weight during the study period
- At baseline, 451 patients were in NYHA Class III and 1069 patients were in NYHA Class II. By the end of the 3 weeks, among those initially in NYHA Class III, 77.16% improved to Class II, and 8.65% improved further to Class I. Only 14.19% remained in Class III. Among the study participants initially in NYHA Class II, 85.41% improved to Class I and 14.59% remained in Class II (Table 1).
Table 1: Change in NYHA functional class in 3 weeks
|
Baseline visit (N = 1520) |
Week 3 Visit |
||
|
NYHA Class III |
NYHA Class II |
NYHA Class I |
|
|
NYHA class III (N = 451) |
64 (14.19) |
348 (77.16) |
39 (8.65) |
|
NYHA class II (N = 1069) |
-- |
156 (14.59) |
913 (85.41) |
- Over three weeks of treatment, patients showed a clear trend toward reduced edema severity. Overall, by the end of treatment, 22.11% of participants had no edema, 32.30% had Grade 1, 25.50% had Grade 2, 13.60% had Grade 3, and only 6.49% remained at Grade 4, highlighting substantial improvement across the cohort (Table 2).
Table 2: Change in edema grades in 3 weeks
|
NYHA Class Baseline visit (N = 1520) |
Edema Grades |
No Edema |
|||
|
Grade 4 n (%) |
Grade 3 n (%) |
Grade 2 n (%) |
Grade 1 n (%) |
|
|
|
Grade 4 (N = 204) |
67 (32.84) |
133 (65.20) |
4 (1.96) |
-- |
-- |
|
Grade 3 (N = 445) |
-- |
78 (17.53)) |
365 (82.02) |
2 (0.45) |
-- |
|
Grade 2 (N = 531) |
-- |
-- |
46 (8.66) |
485 (91.34) |
-- |
|
Grade 1 (N = 340) |
-- |
-- |
-- |
4 (1.18) |
336 (98.82) |
|
Week 3 visit N = 1520 |
67 (4.41) |
211 (13.88) |
415 (27.30) |
491 (32.30) |
336 (22.11) |
- The baseline mean serum creatinine level decreased from 1.19 mg/dL to 0.97 mg/dL at week 3, reflecting a mean reduction of −0.22 mg/dL. Serum sodium levels were stable, with a slight decline from 140.01 mg/dL to 139.62 mg/dL (mean difference −0.36 mg/dL). The serum potassium rose from 4.07 mEq/L at baseline to 4.59 mEq/L at week 3, showing a mean increase of 0.51 mEq/L.
- The incidence of mild AEs was rare (3 cases), no serious AEs or deaths occurred during the study period.
- The therapy was rated as favorable by 98.35% of the physicians and by 98.75% patients (Fig. 2).
Fig. 2: Assessment of the treatment by physicians and patients
Conclusions
- The RESTORE-HF study demonstrated that the FDC of torsemide-spironolactone may be effective and generally well tolerated in Indian heart failure patients.
- Over a period of 3 weeks, patients had a substantial weight loss, improvement in NYHA class, and edema, indicating a significant symptomatic improvement over 3 weeks in real-world clinical practice.
Ther Adv Cardiovasc Dis. 2026 Jan-Dec:20:17539447261430243.
