Relationship between baseline systolic blood pressure and long-term outcomes in acute heart failure patients treated with TRV027: an exploratory subgroup analysis of BLAST-AHF

Clin Res Cardiol. 2018 Feb;107(2):170-181. doi: 10.1007/s00392-017-1168-0. Epub 2017 Oct 6.

Abstract

Introduction: TRV027, a 'biased' ligand of the angiotensin II type 1 receptor (AT1R), did not affect a composite clinical outcome at 30 days in a phase 2b acute heart failure (AHF) trial (BLAST-AHF).

Methods: Post-hoc analyses from BLAST-AHF (n = 618) examined the effects of TRV027 by baseline systolic blood pressure (SBP) on changes in renal function and 180-day outcomes. Interactions between baseline SBP and select endpoints were identified utilizing a subpopulation treatment effect pattern plots (STEPP) analysis, then grouping of patients by SBP tertile: < 127, ≥ 127 to < 140, and ≥ 140 mmHg.

Results: A trend towards increased creatinine in the first 3 days was noted in the lower SBP tertile, while in those in the higher two tertiles, TRV027, especially the 1 mg/h dose, reduced creatinine at days 5 and 30. Beneficial effects on 180-day all-cause mortality and cardiovascular (CV) death or readmission were observed in the two higher SBP tertiles (SBP ≥ 127 mmHg) in the TRV027 1 mg/h dose group (all-cause mortality HR 0.39, 95% CI 0.14-1.06, p = 0.056; CV death or HF/RF rehospitalization HR 0.53, 95% CI 0.28-1.01, p = 0.049), while more adverse outcomes were observed in patients in the lower SBP tertile.

Conclusions: This post-hoc analysis of the BLAST-AHF study suggests contrasting effects of TRV027 by baseline SBP, with trends towards lower 180-day event rates in patients enrolled with higher baseline SBP, especially when given lower doses of TRV027.

Keywords: BLAST-AHF; Blood pressure; Outcomes.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Aged
  • Blood Pressure / drug effects*
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Patient Readmission
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / metabolism
  • Signal Transduction / drug effects
  • Systole
  • Time Factors
  • Treatment Outcome
  • United States

Substances

  • AGTR1 protein, human
  • Cardiovascular Agents
  • Oligopeptides
  • Receptor, Angiotensin, Type 1
  • sarcosine-arginyl-valyl-tyrosyl-isoleucyl-histidyl-prolyl-alanine