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ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.
Leisman, Daniel E; Handisides, Damian R; Busse, Laurence W; Chappell, Mark C; Chawla, Lakhmir S; Filbin, Michael R; Goldberg, Marcia B; Ham, Kealy R; Khanna, Ashish K; Ostermann, Marlies; McCurdy, Michael T; Adams, Christopher D; Hodges, Tony N; Bellomo, Rinaldo.
Afiliación
  • Leisman DE; Department of Medicine, Massachusetts General Hospital, 55 Fruit St., GRB 7-730, Boston, MA, 02114, USA. dleisman@mgh.harvard.edu.
  • Handisides DR; Innoviva Specialty Therapeutics, Inc - an Affiliate of La Jolla Pharmaceutical Company, Waltham, MA, USA.
  • Busse LW; Department of Medicine, Emory University, Atlanta, GA, USA.
  • Chappell MC; Emory Critical Care Center, Emory Healthcare, Atlanta, GA, USA.
  • Chawla LS; Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
  • Filbin MR; Department of Medicine, Veterans Affairs Medical Center, San Diego, CA, USA.
  • Goldberg MB; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Ham KR; Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
  • Khanna AK; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
  • Ostermann M; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
  • McCurdy MT; Division of Infectious Diseases, Department of Medicine, Center for Bacterial Pathogenesis, Massachusetts General Hospital, Boston, MA, USA.
  • Adams CD; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Hodges TN; Department of Critical Care, Mayo Clinic, Phoenix, AZ, USA.
  • Bellomo R; Section on Critical Care Medicine, Department of Anesthesiology, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
Crit Care ; 28(1): 130, 2024 04 18.
Article en En | MEDLINE | ID: mdl-38637829
ABSTRACT

BACKGROUND:

Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock.

METHODS:

In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h.

RESULTS:

We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients.

CONCLUSIONS:

In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier NCT02338843 (Registered January 14th 2015).
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Choque / Inhibidores de la Enzima Convertidora de Angiotensina Límite: Humans Idioma: En Revista: Crit Care Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Choque / Inhibidores de la Enzima Convertidora de Angiotensina Límite: Humans Idioma: En Revista: Crit Care Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos