Key Points

Adjuvant thiazide improved diuretic response more than loop dose increase in patients with acute heart failure and diuretic resistance.The underlying diuretic resistance mechanism did not identify preferential response to either diuretic escalation strategy.

Background

The optimal therapy for loop diuretic resistance may differ if caused by resistance at the site of action in the loop of Henle (diuretic resistance at the loop of Henle [DR-Loop]) versus compensatory distal reabsorption (diuretic resistance due to distal sodium reabsorption [DR-Distal]). This study primarily aimed to compare diuretic strategies and explore whether targeting the underlying diuretic resistance mechanism could optimize diuretic response.

Methods

Patients hospitalized with heart failure and diuretic resistance (6-hour cumulative natriuresis

Results

Patients (mean age 68±12 years, 40% women) were randomized to loop dose intensification (n=51) or adjuvant thiazide (n=52). The primary outcome of increase in 6-hour natriuresis improved significantly with both strategies. However, chlorothiazide addition produced a significantly larger improvement in 6-hour natriuresis (107 mmol increase [95% confidence interval (CI), 81 to 132]) compared with loop augmentation (49 mmol increase [95% CI, 31 to 66]; treatment effect 58 mmol [95% CI, 27 to 89]; P

Conclusions

Strategies of loop dose intensification and adjuvant thiazide both improved diuretic response, with a significantly larger augmentation of natriuresis with adjuvant thiazide. The underlying diuretic resistance mechanism did not identify a preferential response to either therapy.

Clinical Trial registry name and registration number:

ClinicalTrials.gov, Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure NCT02546583.