Why the study?
Vascular decongestion is central in type 1 cardiorenal syndrome, but whether sequential nephron blockade with combined diuretics provides similar renal and decongestive benefits compared to stepped-dose furosemide required investigation.
Does a combined diuretic strategy (chlorthalidone, spironolactone, and furosemide) improve renal function recovery compared to stepped-dose furosemide in patients with type 1 cardiorenal syndrome?
RCT (n=80)
Double-blind
1:1 computer-based stratified by sex
No
Does a combined diuretic strategy (chlorthalidone, spironolactone, and furosemide) improve renal function recovery compared to stepped-dose furosemide in patients with type 1 cardiorenal syndrome?
Relative Risk: 1.5 (95% CI 0.4–5.2)
Absolute Event Rate: 15.2% vs 20%
p-value: p=0.49
In patients with type 1 cardiorenal syndrome, a combined diuretic strategy of chlorthalidone, spironolactone, and furosemide did not significantly improve renal function recovery or vascular decongestion compared to stepped-dose furosemide.
Combined diuretics do not improve renal recovery over stepped furosemide in type 1 cardiorenal syndrome; challenges synergistic blockade and leaves open larger efficacy trials.
AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.
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Chávez-Íñiguez et al. (2022) conducted an RCT in Type 1 Cardiorenal Syndrome (n=80). Combined diuretics vs. Stepped furosemide (continuous infusion of 100 mg day 1, increasing daily up to 400 mg day 4) was evaluated on Renal function recovery (serum creatinine return to baseline value) after 96 hours (RR 1.5, 95% CI 0.4-5.2, p=0.49).
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