Ularitide, an intravenous synthetic form of the renal vasodilatory natriuretic peptide urodilatin, did not improve mortality among patients with acute heart failure, a recent trial found.
The double-blind, industry-funded trial randomized 2,157 patients with acute heart failure to a continuous IV infusion of 15 ng/kg of body weight of ularitide or placebo for 48 hours in addition to usual care. Treatment was initiated a median of six hours after evaluation. Results were published April 12 by the New England Journal of Medicine.
Primary outcomes were death from cardiovascular causes (with a median follow-up of 15 months) and a composite measure of a patient's clinical course during the 48 hours of treatment. The composite was measured at three points during the infusion and included vital status (alive or dead), investigator documentation of persistent or worsening heart failure requiring prespecified interventions, and a patient global assessment.
Rates of cardiovascular death during follow-up were similar between groups (21.7% on ularitide vs. 21.0% on placebo) and an intention-to-treat analysis found no significant difference in the composite 48-hour outcome. The ularitide group did have greater reductions in systolic blood pressure and N-terminal pro-brain natriuretic peptide, but no significant difference in changes in cardiac troponin T levels. Researchers concluded that ularitide exerted favorable physiological effects but that it did not affect the primary outcomes of the study. In addition to not proving effectiveness of the drug, the study “raises doubt about theories that early ventricular distention causes myocardial necrosis and adversely affects the natural history of heart failure after hospitalization and that rapid reversal of short-term ventricular distention preserves myocardial viability,” the study authors said.
An accompanying editorial agreed, noting that “we do not have a mandate to establish rapid-response teams for patients who present with acute decompensated heart failure.” The editorialist added that the study's negative findings should lead physicians to “remind ourselves that the primary immediate objective of treatment is the patient-centric goal of symptom relief.”