Obesity and the response to intensified diuretic treatment in decompensated heart failure: a DOSE trial substudy

Abstract

Background: Obesity could attenuate diuretic effectiveness in treatment of acute decompensated heart failure (HF).

Methods and results: The DOSE trial randomized 308 subjects with acute HF to low- versus high-intensification intravenous diuretic therapy. We tested for statistical interactions between obesity and dosing strategy across clinical end points. After 72 hours of treatment, obese subjects (body mass index >30 kg/m(2); n = 173) had greater volume loss than nonobese subjects (n = 119) but similar improvements in dyspnea and freedom from congestion. Both groups had greater fluid loss with high-intensification treatment. Obese subjects had a higher incidence of worsening renal function (WRF) at 72 hours with low-intensification treatment, compared with nonobese subjects. In contrast, nonobese and obese subjects had similar incidence of WRF with high-intensification treatment. There were no differences between obese and nonobese subjects in time to discharge and 60-day freedom from death, emergency department visit, or rehospitalization.

Conclusions: The incidence of WRF was greater in obese than in nonobese subjects with low-intensification treatment. However, the frequency of WRF was equivalent in obese and nonobese subjects with high-intensification treatment. Additional studies are needed to assess whether obese patients with acute HF benefit from an initial high-intensification treatment strategy.

Figure 1. Change in serum creatinine from baseline to 72 hours

Serum creatinine was measured at baseline, 24, 48 and 72 hours after admission. Data are shown for obese and non-obese subjects randomized to low and high intensification diuretic treatment. Baseline creatinine was not different between the 4 groups. At 72 hours, obese subjects had a greater increase in creatinine than non-obese subjects (P<0.01). Obese subjects receiving low intensification treatment had an increase in creatinine compared to a decrease in the non-obese (p<0.01). Both obese and non-obese assigned to high intensification treatment had a similar rise in creatinine (p=0.34).

Figure 2. Frequency of worsening renal function at 24, 48 and 72 hours after admission

Worsening renal function was defined as increase of serum creatinine by > 0.3 mg/dl above baseline measurement. In the low intensification treatment group, the obese subjects experienced a higher incidence of worsening renal function compared to non-obese. In the high intensification treatment arm, both obese and non-obese subjects had similar incidence of worsening renal function. P-value for BMI x intensification strategy interaction = 0.01.

Figure 3

Kaplan Meier plot of time to composite endpoint (emergency room visit, rehospitalization or death). There was no significant difference in the 60 day event rate between the obese and non-obese groups.