Short-Term Effects of Pecavaptan on Weight and Congestion in Acute Heart Failure: The AVANTI Post-Hoc Analysis

Pecavaptan, a dual vasopressin V1a/V2-receptor antagonist, did not enhance weight loss by day 30 in hospitalized heart failure (HF) patients. However, its short-term effects remain unclear.

The objective of the study was to evaluate pecavaptan's effect on weight loss and congestion after 7 days.

AVANTI was a double-blind, randomized, placebo-controlled trial in patients hospitalized with HF and incomplete decongestion (n = 482). In part A, patients received pecavaptan (30 mg) (n = 242) or placebo (n = 240) as adjunctive therapy for 30 days. In this post hoc analysis, baseline-adjusted differences in weight change and a composite congestion score (CCS) at day 7 were calculated using analysis of covariance. Individual CCS component effects were assessed using baseline-adjusted ordinal regression at day 7.

Patients had a median age of 70 years (IQR: 62.0-78.0) and 24% (118/482) were women. Pecavaptan resulted in greater weight loss vs placebo by day 7 (-1.43 kg vs -0.95 kg; difference -0.47 kg; 95% CI: -0.94 to -0.01; P = 0.044). Although the CCS was not significantly modified by pecavaptan at day 7 (P = 0.171), we observed a better resolution of pedal edema (adjusted OR: 0.63; 95% CI: 0.42-0.95; nominal P = 0.026) and reduced thoracic fluid content (difference: -1.43%; 95% CI: -2.57 to -0.28; nominal P = 0.015) at day 7. These effects were limited and no longer significant by day 30. An increase in plasma osmolality and serum sodium concentration by pecavaptan was observed at day 7 and day 30 (both P < 0.01).

In patients hospitalized for acute HF with residual congestion, pecavaptan showed modest signals of early decongestion, without durable benefit at 30 days. These post hoc findings require prospective confirmation. (A Trial to Study BAY1753011 in Patients With Congestive Heart Failure [AVANTI]; NCT03901729).