High Furosemide Dose has Detrimental Effects on Survival of Patients with Stable Heart Failure

Introduction: High doses of furosemide for heart failure (HF) have been correlated with an increased mortality, though whether they are a marker of disease severity or an independent predictor is unknown. We hypothesized that, in patients presenting with stable HF, the likelihood of long-term major adverse clinical events is increased by higher furosemide doses. Methods: We retrospectively recorded the doses of furosemide prescribed to 173 consecutive, clinically stable patients during a first ambulatory HF department visit. The low-dose group included 103 patients treated with <= 80 mg and the high-dose group included 70 patients treated with >80 mg of furosemide daily. Proportional hazard regression analyses were performed with single and multiple variables in search of correlates of long-term adverse clinical events. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: The baseline characteristics of the 2 groups were similar, except for estimated glomerular filtration rate, which was higher in the low-than the high-dose group (72.9 +/- 19.4 vs. 60.8 +/- 22.0 mL/min/m(2), p<0.001). The 3-year survival free from the composite endpoint was significantly higher in the low-dose group than in the high-dose group (93.1% vs. 60.0%, p<0.001). By multiple variable analysis, high-dose furosemide was an independent predictor of an adverse outcome at 3 years (adjusted HR: 15.25; 95% CI: 1.06-219.39, p=0.045). The incidence of deterioration of renal function and episodes of hypokalemia during follow up was also higher in the high furosemide dose (73.2% vs. 48.3, p=0.003, and 43.1% vs. 6.5%, p<0.001, respectively). Conclusions: High doses of furosemide administered in order to stabilize HF patients and continued thereafter are associated with an adverse clinical outcome.