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

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.

Author information

1
Momentum Research Inc., Suite 801, 3100 Tower Blvd, Durham, NC, 27707, USA. gadcotter@momentum-research.com.
2
Momentum Research Inc., Suite 801, 3100 Tower Blvd, Durham, NC, 27707, USA.
3
SUNY Stony Brook School of Medicine, New York, NY, USA.
4
Vanderbilt University, Nashville, TN, USA.
5
University of Alberta, Edmonton, AB, Canada.
6
Duke University School of Medicine and the Duke Clinical Research Institute, Durham, NC, USA.
7
Department of Cardiology, School of Medicine, Heart Failure Unit, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
8
Wayne State University School of Medicine and Cardiovascular Research Institute, Detroit, MI, USA.
9
Cardiology, University of Brescia, Brescia, Italy.
10
Medical University, Clinical Military Hospital, Wroclaw, Poland.
11
Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, CA, USA.
12
University of Groningen, Groningen, The Netherlands.
13
Allergan plc (Forest Labs), Jersey City, NJ, USA.
14
Trevena Inc, King of Prussia, PA, USA.
15
Indiana University School of Medicine and Regenstrief Institute, Indianapolis, IN, USA.

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

PMID:
28986703
DOI:
10.1007/s00392-017-1168-0
[Indexed for MEDLINE]

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