Prognostic Effect of the Dose of Loop Diuretic Over 5 Years in Chronic Heart Failure

•Individual diuretic dose adjustments were frequent over the course of the disease.•At individually optimized doses, chronic diuretic therapy did not impair survival.•Diuretic dose was associated with the severity of the patient's clinical condition. High diuretic doses in chronic heart failure (HF) are potentially deleterious. We assessed the effect of dynamic furosemide dose on all-cause mortality among HF ambulatory patients. A cohort of 560 ambulatory patients from an outpatient clinic specialized in HF, with median age 70 years, 67% male, and 89% with moderate-severely reduced ejection fraction, was retrospectively followed for up to 5 years. Dynamic furosamide exposure was categorized as low (0–59 mg/d), medium (60–119 mg/d), high (120–159 mg/d), and very high (≥160 mg/d). Extended Cox models were used to estimate the association between time-varying diuretic dose and mortality. A dose-dependent crude association between higher doses of furosemide and death (hazard ratio [HR] = 1.34, 95% confidence interval (CI): 1.06–2.16; HR = 2.09, 95% CI: 1.54–2.84, for high and very high dose, respectively) was totally explained by patients' characteristics and disease severity indicators (adjusted HR = 0.94, 95% CI: 0.63–1.38; HR = 1.10, 95% CI: 0.79–1.55, for high and very high dose, respectively). In this context, higher doses of diuretic did not impair survival, but rather indicated greater severity of the patient's condition.