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

Gad Cotter, Beth A. Davison, Javed Butler, Sean P. Collins, Justin A. Ezekowitz, G. Michael Felker, Gerasimos Filippatos, Phillip D. Levy, Marco Metra, Piotr Ponikowski, John R. Teerlink, Adriaan A. Voors, Stefanie Senger, David Bharucha, Kathleen Goin, David G. Soergel, Peter Pang

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalClinical Research in Cardiology
DOIs
StateAccepted/In press - Oct 6 2017

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Heart Failure
Blood Pressure
sarcosine-arginyl-valyl-tyrosyl-isoleucyl-histidyl-prolyl-alanine
Creatinine
Angiotensin Type 1 Receptor
Mortality
Ligands
Hypertension
Kidney

Keywords

  • BLAST-AHF
  • Blood pressure
  • Outcomes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Cotter, Gad; Davison, Beth A.; Butler, Javed; Collins, Sean P.; Ezekowitz, Justin A.; Felker, G. Michael; Filippatos, Gerasimos; Levy, Phillip D.; Metra, Marco; Ponikowski, Piotr; Teerlink, John R.; Voors, Adriaan A.; Senger, Stefanie; Bharucha, David; Goin, Kathleen; Soergel, David G.; Pang, Peter.

In: Clinical Research in Cardiology, 06.10.2017, p. 1-12.

Research output: Contribution to journalArticle

Cotter, G, Davison, BA, Butler, J, Collins, SP, Ezekowitz, JA, Felker, GM, Filippatos, G, Levy, PD, Metra, M, Ponikowski, P, Teerlink, JR, Voors, AA, Senger, S, Bharucha, D, Goin, K, Soergel, DG & Pang, P 2017, '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', Clinical Research in Cardiology, pp. 1-12. https://doi.org/10.1007/s00392-017-1168-0
Cotter, Gad ; Davison, Beth A. ; Butler, Javed ; Collins, Sean P. ; Ezekowitz, Justin A. ; Felker, G. Michael ; Filippatos, Gerasimos ; Levy, Phillip D. ; Metra, Marco ; Ponikowski, Piotr ; Teerlink, John R. ; Voors, Adriaan A. ; Senger, Stefanie ; Bharucha, David ; Goin, Kathleen ; Soergel, David G. ; Pang, Peter. / 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. In: Clinical Research in Cardiology. 2017 ; pp. 1-12.
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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.",
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T2 - an exploratory subgroup analysis of BLAST-AHF

AU - Cotter, Gad

AU - Davison, Beth A.

AU - Butler, Javed

AU - Collins, Sean P.

AU - Ezekowitz, Justin A.

AU - Felker, G. Michael

AU - Filippatos, Gerasimos

AU - Levy, Phillip D.

AU - Metra, Marco

AU - Ponikowski, Piotr

AU - Teerlink, John R.

AU - Voors, Adriaan A.

AU - Senger, Stefanie

AU - Bharucha, David

AU - Goin, Kathleen

AU - Soergel, David G.

AU - Pang, Peter

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N2 - 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.

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