Abstract 21227: Plasma Renin Activity, Response to Aliskiren, and Clinical Outcomes in Patients Hospitalized for Heart Failure: The ASTRONAUT Trial

Background: The direct renin inhibitor, aliskiren, is known to reduce plasma renin activity (PRA), but whether the efficacy of aliskiren varies based on an individual’s baseline PRA in patients hospitalized for HF is presently unknown. We characterized the prognostic value of PRA and determined if this risk is modifiable with use of aliskiren. Methods: This pre-specified neurohormonal substudy of ASTRONAUT analyzed all patients hospitalized for HF with EF≤ 40% with available baseline PRA data (n=1,306, 80.9%). Risk associated with baseline PRA and short-term changes in PRA from baseline to 1-month was modeled with respect to 12-month clinical events. Results: Median baseline PRA was 3.0 (interquartile range 0.6-16.4) ng/mL/h with marked regional heterogeneity (P<0.001); Figure . Aliskiren significantly reduced PRA early after treatment initiation through 12-month follow-up compared with placebo (P<0.001). The lowest baseline PRA quartile (<0.6 ng/mL/h) was independently predictive of lower all-cause mortality (adj. HR 0.50, 95% CI 0.31-0.81) and the composite of CV mortality and HF hospitalization (adj. HR 0.57, 95% CI 0.40-0.79); Table . Delta log-normalized PRA (from baseline to 1 month) was not predictive of either primary endpoint at 12 months (P≥0.43). The prognostic value of baseline PRA and short-term changes in PRA did not vary by randomization to aliskiren or placebo (interaction P≥0.13). Conclusions: PRA is reduced early and durably by aliskiren, but this did not appear to translate into improved clinical outcomes in ASTRONAUT. Baseline PRA or short-term reduction in PRA do not identify a subgroup which may preferentially benefit from direct renin inhibition.