Diuretic resistance predicts mortality in patients with advanced heart failure

Background: In patients with chronic heart failure (CHF), diuretic requirements increase as the disease progresses. Because diuretic resistance can be overcome with escalating doses, the evaluation of CHF severity and prognosis may be incomplete without considering the intensity of therapy. Methods: The prognostic importance of diuretic resistance (as evidenced by a high-dose requirement) was retrospectively evaluated in 1153 patients with advanced CHF who were enrolled in the Prospective Randomized Amlodipine Survival Evaluation (PRAISE). The relation of loop diuretic and angiotensin-converting enzyme inhibitor doses (defined by their median values) and other baseline characteristics to total and cause-specific mortality was determined by proportion hazards regression. Results: High diuretic doses were independently associated with mortality, sudden death, and pump failure death (adjusted hazard ratios [HRs] 1.37 [P = .004], 1.39 [P = .042], and 1.51 [P = .034], respectively). Use of metolazone was an independent predictor of total mortality (adjusted HR = 1.37, P = .016) but not of cause-specific mortality. Low angiotensin-converting enzyme inhibitor dose was an independent predictor of pump failure death (adjusted HR = 2.21, P = .0005). Unadjusted mortality risks of congestion and its treatment were additive and comparable to those of established risk factors. Conclusions: The independent association of high diuretic doses with mortality suggests that diuretic resistance should be considered an indicator of prognosis in patients with chronic CHF. These retrospective observations do not establish harm or rule out a long-term benefit of diuretics in CHF, because selection bias may entirely explain the relation of prescribed therapy to death.