Diuretic dose trajectories in dilated cardiomyopathy: prognostic implications

Background: For patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM).

Methods: Associations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by < 50%); and (iv) never-users. The primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. The secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device.

Results: Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04-1.22], p = 0.003). Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19-4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27-6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28-0.65], p < 0.001).

Conclusions: In patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis. Among 1131 DCM patients 65% received loop diuretics at enrolment (upper left side). The bar chart on the upper right side shows the categorization in never-users/ dose↓/stable dose/ dose↑ over 24 months of follow-up. At the bottom is reported on the left side of each panel (observation period) the trajectory of LD dose in the four groups (left panel) and in patients who have their LD suspended vs those who continue LD (right panel) in the first two years. On the right side of each panel is shown the incidence of primary outcomes during the subsequent follow-up in the subgroups (outcome assessment).