Evidence map›Paper›PMID 31707802›Full record

ArticleCirculation. Heart failure2019

Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor Sacubitril/Valsartan.

Richard T Clements, Alexander Vang, Ana Fernandez-Nicolas, Nouaying R Kue, Thomas J Mancini, Alan R Morrison, Krishna Mallem, Danielle J McCullough, Gaurav Choudhary

Open access · bronzeAbstract read
In one paragraph

Article in Circulation. Heart failure, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Richard T ClementsVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
Alexander VangVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
Ana Fernandez-NicolasVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
Nouaying R KueVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
Thomas J ManciniVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
Alan R MorrisonVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
Krishna MallemVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
Danielle J McCulloughDepartment of Anatomical Sciences, Edward Via College of Osteopathic Medicine-Auburn Campus, AL (D.J.M.).
Gaurav ChoudharyVascular Research Laboratory, Providence VA Medical Center, RI (R.T.C., A.V.A.B., A.F.-N., N.R.K., T.J.M., A.R.M., K.M., G.C.).
University of Rhode Island · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Tracking and Evaluation CoreU54GM115677 · NIGMS · BROWN UNIVERSITY · PI KOGUT, STEPHEN J · 2016 to 2025
$45.0M
Uncoupling of IL-1 beta and VEGF-A Crosstalk Contributes to Impaired Arteriogenesis Response to Ischemia in Chronic Diabetes MellitusP20GM103652 · NIGMS · OCEAN STATE RESEARCH INSTITUTE, INC. · PI HARRINGTON, ELIZABETH O · 2013 to 2022
$21.3M
Surgical Cardioprotection Through BKCa-Dependent Modulation of Mitochondrial SupercomplexesR01HL135236 · NHLBI · UNIVERSITY OF RHODE ISLAND · PI CLEMENTS, RICHARD T · 2018 to 2021
$1.9M
Development of Rac-Targeted Therapeutic Strategy for Treatment of Calcific AtherosclerosisR01HL139795 · NHLBI · OCEAN STATE RESEARCH INSTITUTE, INC. · PI MORRISON, ALAN ROSS · 2018 to 2022
$1.8M
Role of Endothelial Anoctamin-1 in Pulmonary Arterial HypertensionR01HL148727 · NHLBI · OCEAN STATE RESEARCH INSTITUTE, INC. · PI CHOUDHARY, GAURAV · 2019 to 2022
$1.6M
Nicotinic Acetylcholine Receptors and RV Dysfunction in Pulmonary HypertensionR01HL128661 · NHLBI · OCEAN STATE RESEARCH INSTITUTE, INC. · PI CHOUDHARY, GAURAV · 2015 to 2018
$1.3M
CSRD VA I01 CX001892NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL128661NHLBI NIH HHS R01 HL135236NHLBI NIH HHS R01 HL139795NHLBI NIH HHS R01 HL148727NIGMS NIH HHS P20 GM103652NIGMS NIH HHS U54 GM115677
6 · The paper itself

Abstract

backgroundAngiotensin II has been implicated in maladaptive right ventricular (RV) hypertrophy and fibrosis associated with pulmonary hypertension (PH). Natriuretic peptides decrease RV afterload by promoting pulmonary vasodilation and inhibiting vascular remodeling but are degraded by neprilysin. We hypothesized that angiotensin receptor blocker and neprilysin inhibitor, sacubitril/valsartan (Sac/Val, LCZ696), will attenuate PH and improve RV function by targeting both pulmonary vascular and RV remodeling.

methodsPH was induced in rats using the SU5416/hypoxia model (Su/Hx), followed by 6-week treatment with placebo, Sac/Val, or Val alone. There were 4 groups: CON-normoxic animals with placebo (n=18); PH-Su/Hx rats+placebo (n=34); PH+Sac/Val (N=24); and PH+Val (n=16).

resultsIn animals with PH, treatment with Sac/Val but not Val resulted in significant reduction in RV pressure (mm Hg: PH: 62±4, PH+Sac/Val: 46±5), hypertrophy (RV/LV+S: PH: 0.74±0.06, PH+Sac/Val: 0.46±0.06), collagen content (µg/50 µg protein: PH: 8.2±0.3, PH+Sac/Val: 6.4±0.4), pressures and improvement in RVs (mm/s: PH: 31.2±1.8, PH+Sac/Val: 43.1±3.6) compared with placebo. This was associated with reduced pulmonary vascular wall thickness, increased lung levels of ANP (atrial natriuretic peptide), BNP (brain-type natriuretic peptide), and cGMP, and decreased plasma endothelin-1 compared with PH alone. Also, PH+Sac/Val animals had altered expression of PKC isozymes in RV tissue compared with PH alone.

conclusionsSac/Val reduces pulmonary pressures, vascular remodeling, as well as RV hypertrophy in a rat model of PH and may be appropriate for treatment of pulmonary hypertension and RV dysfunction.

Indexed as

AminobutyratesAngiotensin II Type 1 Receptor BlockersAnimalsAntihypertensive AgentsArterial PressureBiphenyl CompoundsDisease Models, AnimalDrug CombinationsFemaleFibrosisHypertension, PulmonaryHypertrophy, Right VentricularMaleNeprilysinProtease InhibitorsPulmonary ArteryAminobutyratesAngiotensin II Type 1 Receptor BlockersAntihypertensive AgentsBiphenyl CompoundsDrug CombinationsNeprilysinProtease Inhibitorssacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanangiotensinfibrosishypertension, pulmonarymodels, animalnatriuretic peptidesvasodilation

Identifiers

PMID31707802
PMCPMC6857845
OpenAlexW2985079693

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.