Levosimendan vs. dobutamine: outcomes for acute heart failure patients on beta-blockers in SURVIVE

Abstract

Aims: Many chronic heart failure (CHF) patients take beta-blockers. When such patients are hospitalized for decompensation, it remains unclear how ongoing beta-blocker treatment will affect outcomes of acute inotrope therapy. We aimed to assess outcomes of SURVIVE patients who were on beta-blocker therapy before receiving a single intravenous infusion of levosimendan or dobutamine.

Methods and results: Cox proportional hazard regression revealed all-cause mortality benefits of levosimendan treatment over dobutamine when the SURVIVE population was stratified according to baseline presence/absence of CHF history and use/non-use of beta-blocker treatment at baseline. All-cause mortality was lower in the CHF/levosimendan group than in the CHF/dobutamine group, showing treatment differences by hazard ratio (HR) at days 5 (3.4 vs. 5.8%; HR, 0.58, CI 0.33-1.01, P = 0.05) and 14 (7.0 vs. 10.3%; HR, 0.67, CI 0.45-0.99, P = 0.045). For patients who used beta-blockers (n = 669), mortality was significantly lower for levosimendan than dobutamine at day 5 (1.5 vs. 5.1% deaths; HR, 0.29; CI 0.11-0.78, P = 0.01).

Conclusion: Levosimendan may be better than dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations. These findings are preliminary but important for planning future studies.

Figure 1

(A) Hazard ratios for all-cause mortality up to 31 days in all acute heart failure patients who were treated with levosimendan (n = 663) or dobutamine (n = 664) in the SURVIVE trial. These data include patients with acute decompensation of chronic heart failure as well as those with acute de novo heart failure. P-values shown were derived by the Cox proportional hazards model with effect for treatment only. Data represent the intent-to-treat population. (B) Hazard ratios for all-cause mortality up to 31 days in the SURVIVE trial with stratification according to whether or not patients had a history of chronic heart failure (HF). This analysis included patients who were treated with levosimendan (n = 586 with history of HF; n = 78 without history of HF) or dobutamine (n = 585 with history of HF; n = 78 without history of HF). P-values shown were derived by the Cox model with effect for treatment only. P-values for treatment × subgroup interactions were 0.10, 0.01, and 0.046 at days 5, 14, and 31, respectively. (C) Hazard ratios for all-cause mortality up to 31 days in the SURVIVE trial with stratification according to β-blocker status at the start of the trial. The analysis included acute heart failure patients who were treated with levosimendan (n = 336 β-blocker users; n = 328 β-blocker non-users) or dobutamine (n = 333 β-blocker users; n = 330 β-blocker non-users).

Figure 2

Haemodynamic parameters according to prior use or non-use of β-blockers and to treatment. (A)–(C), respectively, are heart rate, systolic and diastolic blood pressure, shown as mean changes from baseline (±standard error) during 5 days after the start of treatment.