Increased Mortality after Dronedarone Therapy for Severe Heart Failure
Why the study?
Does dronedarone reduce the composite of death from any cause or hospitalization for heart failure in patients hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction?
Population
627 patients hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction
Comparison
Dronedarone 400 mg twice a day vs Placebo
Design
RCT, randomly assign, double-blind
Follow-up
median 2 months
Authors
Discussion
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Member takes
Implication
Avoid dronedarone in severe systolic HF with LV dysfunction; challenges antiarrhythmic safety assumptions and closes this indication.
Key Points
- To assess the efficacy and safety of dronedarone in reducing mortality and hospitalization among patients with symptomatic heart failure and severe left ventricular systolic dysfunction.
- Multicenter, double-blind randomized trial (NCT00543699) designed to assign 1,000 hospitalized patients with symptomatic heart failure and severe left ventricular systolic dysfunction to dronedarone (400 mg twice daily) or placebo.
- The primary composite endpoint was death from any cause or hospitalization for heart failure, evaluated over a median follow-up of 2 months before early termination.
- All-cause mortality was significantly higher with dronedarone than placebo (8.1% [25/310] vs. 3.8% [12/317]; HR, 2.13; 95% CI, 1.07 to 4.25; P=0.03), primarily driven by worsening heart failure (10 vs. 2 deaths).
- The primary composite endpoint of death or heart failure hospitalization showed no significant difference between the dronedarone and placebo groups (17.1% [53/310] vs. 12.6% [40/317]; HR, 1.38; 95% CI, 0.92 to 2.09; P=0.12).
- The trial was stopped prematurely after enrolling 627 patients due to excess mortality and serious adverse events related to increased creatinine levels in the dronedarone group.
Structured PICO
Does dronedarone reduce the composite of death from any cause or hospitalization for heart failure in patients hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction?
P
Population
627 patients hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction
I
Intervention
Dronedarone 400 mg twice a day
C
Comparator
Placebo
O
Outcome
Composite of death from any cause or hospitalization for heart failurecomposite
In patients with severe heart failure and left ventricular systolic dysfunction, dronedarone therapy is associated with increased early mortality, primarily due to worsening heart failure.
Limitations
- Prematurely terminated for safety reasons
Cite This Study
Køber et al. (2008) studied this question.