Loop diuretics, renal function and clinical outcome in patients with heart failure and reduced ejection fraction

Aim: We aimed to study the relationships of loop diuretic dose with renal function and clinical outcomes in patients with chronic heart failure ( HF ). Methods and results: Loop diuretic dose at baseline was recorded in patients included in the Controlled Rosuvastatin Multinational Trial in Heart Failure ( CORONA ). The relationship to change in estimated glomerular filtration rate ( eGFR ) over time and to the first occurrence of the composite outcome of cardiovascular ( CV ) death or hospitalization owing to HF was examined in propensity score matched cohorts. Of the 5011 patients, 2550, 745, and 449 were receiving > 80 mg ( high ), 41–80 mg ( medium ) and ≤40 mg ( low ) of loop diuretics in furosemide equivalent daily dosages, respectively, which were used to assemble 229, 385, and 1045 pairs of propensity-matched high, medium, and low dose cohorts. Compared with matched no loop diuretic groups, eGFR declined 0.3 ± 0.2, 0.3 ± 0.3 and 1.2 ± 0.5 mL/min/1.73 m2/year in the low-, medium-, and high-dose groups, respectively. Compared with matched no loop diuretic groups, hazard ratios ( HR ) ( 95% confidence intervals ) for outcome associated with low-, medium- and high-dose groups were 1.71 ( 1.41–2.06 ), 1.99 ( 1.50–2.64 ), and 2.94 ( 1.95–4.41 ), respectively. Higher loop diuretic dose was particularly associated with increased risk for hospitalization owing to HF: HR 4.80 ( 2.75–8.37 ), P  <  0.001. Conclusions: The use of loop diuretics was associated with a slightly greater rate of decline in eGFR, which did not vary significantly by diuretic dose. Loop diuretic dose was associated with higher risks of ( CV ) mortality and predominantly hospitalization owing to HF, which appeared to be higher among those receiving higher daily doses.