Evidence map›Paper›PMID 38637829›Full record

Trial reportCritical care (London, England)2024

ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

Daniel E Leisman, Damian R Handisides, Laurence W Busse, Mark C Chappell, Lakhmir S Chawla, Michael R Filbin, Marcia B Goldberg, Kealy R Ham, Ashish K Khanna, Marlies Ostermann and 5 more

2 registry-linked trialsOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Critical care (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
10.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02338843 phase3completednot on this map

A Phase 3, Placebo-Controlled, Randomized, Double-Blind, Multi-Center Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension (CRH)

TypeinterventionalSponsorLa Jolla Pharmaceutical CompanyRan2015 to 2017Enrolled344ConditionsCatecholamine-resistant Hypotension (CRH), Distributive Shock, High Output Shock, SepsisArmsLJPC-501, Placebo
NCT06539234 recruitingnot on this map

Angiotensin II Stress Test. Renin Kinetics During Treatment of Vasoplegic Shock With Angiotensin II in Relation to Hemodynamic Response to Treatment With Angiotensin II.

TypeobservationalSponsorUniversity Medical Centre MariborRan2024 to 2026Enrolled80ConditionsShock, Vasoplegic Syndrome
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
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  11. Cross talk on therapeutic strategies: natriuretic peptides and inhibiting neprilysin in hypertension management.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
    Review
  12. Review
  13. Article
  14. Review
  15. Renin in critically ill patients.Annals of intensive care · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 12 institutions in 3 countries.

Daniel E LeismanDepartment of Medicine, Massachusetts General Hospital, 55 Fruit St., GRB 7-730, Boston, MA, 02114, USA. dleisman@mgh.harvard.edu.
Damian R HandisidesInnoviva Specialty Therapeutics, Inc - an Affiliate of La Jolla Pharmaceutical Company, Waltham, MA, USA.
Laurence W BusseDepartment of Medicine, Emory University, Atlanta, GA, USA.
Mark C ChappellHypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Lakhmir S ChawlaDepartment of Medicine, Veterans Affairs Medical Center, San Diego, CA, USA.
Michael R FilbinDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Marcia B GoldbergBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Kealy R HamDepartment of Critical Care, Mayo Clinic, Phoenix, AZ, USA.
Ashish K KhannaSection on Critical Care Medicine, Department of Anesthesiology, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
Marlies OstermannDepartment of Critical Care, King's College London, Guy's & St Thomas' Hospital, London, UK.
Michael T McCurdyDivision of Pulmonary & Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Christopher D AdamsInnoviva Specialty Therapeutics, Inc - an Affiliate of La Jolla Pharmaceutical Company, Waltham, MA, USA.
Tony N HodgesInnoviva Specialty Therapeutics, Inc - an Affiliate of La Jolla Pharmaceutical Company, Waltham, MA, USA.
Rinaldo BellomoAustralian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
ATHOS-3 Investigators
La Jolla Pharmaceutical (United States) · USAtrium Health Wake Forest Baptist · USBroad Institute · USEmory Healthcare · USHarvard University · USMassachusetts General Hospital · USMayo Clinic Hospital · USMonash University · AUSan Francisco VA Medical Center · USSt Thomas' Hospital · GBUniversity of Maryland, Baltimore · USWake Forest University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAngiotensin-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.

methodsIn 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.

resultsWe 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], p

conclusionsIn 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).

Indexed as

Angiotensin-Converting Enzyme InhibitorsShockAngiotensin IIAngiotensin Receptor AntagonistsHumansNorepinephrineReninAngiotensin-Converting Enzyme InhibitorsAngiotensin IIAngiotensin Receptor AntagonistsNorepinephrineReninAngiotensin IINorepinephrineRenin–angiotensin systemSepticShock

Identifiers

PMID38637829
PMCPMC11027368
OpenAlexW4394912413

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.