A practical approach to sequential nephron blockade in acute decompensated heart failure
Article Category: Review
Published Online: Sep 21, 2023
Page range: 83 - 92
DOI: https://doi.org/10.2478/rjc-2023-0021
Keywords
© 2023 Georgiana-Valentina Frățilă et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Combined diuretic strategies to overcome anticipated adverse events.
| Class of medication | Anticipated electrolyte or acid-base disturbances | Add-on diuretic agents to counteract the anticipated primary adverse event |
|---|---|---|
| Thiazide diuretics Loop diuretics | Hyponatremia | SGLT2i Vasopressin receptor antagonists |
| Thiazide diuretics Loop diuretics | Hypokalemia | MRAs |
| RAASi MRAs ENaC blockers | Hyperkalemia | SGLT2i Loop or thiazide diuretics |
| Thiazide diuretics Loop diuretics | Metabolic alkalosis | CA inhibitors MRAs |
| CA inhibitors MRAs | Metabolic acidosis | Thiazide diuretics Loop diuretics |
| Thiazide diuretics Loop diuretics | Hypomagnesemia | MRAs ENaC blockers |
| CA inhibitors Loop diuretics | Hypocalcemia | Thiazide diuretics ENaC blockers |
Trials evaluating sequential nephron blockade.
| Site of additional blockade | Trial | Background diuretics | Additional comparator agent versus placebo | Primary endpoint | Results | Additional findings |
|---|---|---|---|---|---|---|
| Proximal nephron blockade | EMPA-RESPONSE-AHF [ |
Loop diuretics | Empagliflozin (10 mg) |
Change in dyspnea Diuretic response Change in NT-proBNP Length of stay |
No difference in any of the primary endpoint events |
Lower incidence of a combined endpoint of inhospital worsening of HF, rehospitalization for HF and mortality at 60 days. Greater urinary output with empagliflozin |
| EMPAG-HF [ |
Loop diuretics | Empagliflozin (25 mg) |
Cumulative urinary output over 5 days |
25% increase in cumulative urine output over 5 days |
Empagliflozin increased diuretic efficiency compared with placebo, with more pronounced decrease in NT-proBNP |
|
| EMPULSE [ |
Loop diuretics | Empagliflozin (10 mg) |
Weight loss Weight loss adjusted per mean daily loop diuretic dose Change in NT-proBNP Hemoconcentration Clinical congestion score |
Empagliflozin demonstrated significantly greater reductions in all studied markers of decongestion at all time-points |
Greater weight loss at Day 15 was associated with significantly higher probability for clinical benefit at Day 90 (composite endpoint of all-cause death, heart failure events, and a 5- point or greater difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline to 90 days) |
|
| DIURESIS-CHF [ |
Loop diuretics | Acetazolamide |
Natriuresis after 24 h |
Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm |
Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide |
|
| ADVOR [ |
Loop diuretics | Acetazolamide |
Successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy |
Patients with acetazolamide add-on achieved more frequently successful decongestion both within 3 days after randomization (42.2% vs. 30.5%) and at discharge (78.8% vs. 62.5%). |
Acetazolamide led to a greater urinary output and natriuresis Acetazolamide did not decrease the risk of death or rehospitalization for HF |
|
| Distal nephron blockade | CLOROTIC [ |
Loop diuretics | Hydrochlorothiazide |
Change in dyspnea Change in body weight |
Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo, but there were no significant differences in patient-reported dyspnea |
Patients allocated to HCTZ showed greater 24-h diuresis and weight loss for each 40 mg of furosemide There were no differences in mortality or rehospitalizations |
| ATHENA-HF [ |
Standard therapy that may include low-dose spironolactone (12.5 or 25 mg) | Spironolactone 100 mg |
Change in NT-proBNP levels from baseline to 96 hours |
No significant difference in the log NT-proBNP reduction between the 2 groups |
No significant change in clinical congestion score, dyspnea assessment, urinary output, weight change, mortality or rehospitalization for HF. |
|
| EVEREST [ |
Standard therapy | Tolvaptan |
All-cause mortality Cardiovascular death or hospitalization for HF |
Tolvaptan had no effect on long-term mortality or heart failure–related morbidity |
Tolvaptan improved day 1 patient-assessed dyspnea, day 1 body weight, day 7 edema. |
|
| Distal nephron blockade | TACTICS-HF [ |
Loop diuretics | Tolvaptan |
Proportion of patients with at least moderate improvement in dyspnea by 7-point Likert scale at both 8 and 24 h, without death or need for rescue therapy within 24 h (defined as responders) |
The proportion defined as responders at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo ( |
Tolvaptan addition resulted in greater weight loss and net fluid loss compared with placebo |
| SECRET of CHF [ |
Loop diuretics | Tolvaptan |
7-point change in self-assessed dyspnea at 8 and 16 h |
No difference in the primary endpoint of day 1 dyspnea reduction |
Tolvaptan led to a significantly greater weight loss and dyspnea reduction at day 3. |