Evidence map›Paper›PMID 37169384›Full record

SynthesisThe European respiratory journal2023

Heterogeneity of treatment effects by risk in pulmonary arterial hypertension.

Hao-Min Pan, Robyn L McClelland, Jude Moutchia, Dina H Appleby, Jason S Fritz, John H Holmes, Jasleen Minhas, Harold I Palevsky, Ryan J Urbanowicz, Steven M Kawut and 1 more

Open access · greenAbstract readMeta-Analysis
In one paragraph

Synthesis in The European respiratory journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Treatment algorithm for pulmonary arterial hypertension.The European respiratory journal · 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

11 authors at 3 institutions in 1 country.

Hao-Min PanDepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Robyn L McClellandDepartment of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA.
Jude MoutchiaDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Dina H ApplebyDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Jason S FritzDepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
John H HolmesDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Jasleen MinhasDepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Harold I PalevskyDepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Ryan J UrbanowiczDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Steven M KawutDepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-7896-0608
Nadine Al-NaamaniDepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA nadine.al-naamani@pennmedicine.upenn.edu.ORCID 0000-0002-0437-3213
University of Pennsylvania · USCedars-Sinai Medical Center · USUniversity of Washington · US

Funding

Cardiology & pulmonary research training grantT32HL007891 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Jason D Christie · 1998 to 2026
$12.0M
Mentored Patient-Oriented Research in Pulmonary Arterial HypertensionK24HL103844 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KAWUT, STEVEN M · 2011 to 2020
$1.6M
Obesity in Pulmonary Arterial HypertensionK23HL141584 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI AL-NAAMANI, NADINE · 2018 to 2022
$970k
NHLBI NIH HHS K23 HL141584NHLBI NIH HHS K24 HL103844NHLBI NIH HHS T32 HL007891
6 · The paper itself

Abstract

backgroundIt is currently unknown if disease severity modifies response to therapy in pulmonary arterial hypertension (PAH). We aimed to explore if disease severity, as defined by established risk-prediction algorithms, modified response to therapy in randomised clinical trials in PAH.

methodsWe performed a meta-analysis using individual participant data from 18 randomised clinical trials of therapy for PAH submitted to the United States Food and Drug Administration to determine if predicted risk of 1-year mortality at randomisation modified the treatment effect on three outcomes: change in 6-min walk distance (6MWD), clinical worsening at 12 weeks and time to clinical worsening.

resultsOf 6561 patients with a baseline US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL 2.0) score, we found that individuals with higher baseline risk had higher probabilities of clinical worsening but no difference in change in 6MWD. We detected a significant interaction of REVEAL 2.0 risk and treatment assignment on change in 6MWD. For every 3-point increase in REVEAL 2.0 score, there was a 12.49 m (95% CI 5.86-19.12 m; p=0.001) greater treatment effect in change in 6MWD. We did not detect a significant risk by treatment interaction on clinical worsening with most of the risk-prediction algorithms.

conclusionsWe found that predicted risk of 1-year mortality in PAH modified treatment effect as measured by 6MWD, but not clinical worsening. Our findings highlight the importance of identifying sources of treatment heterogeneity by predicted risk to tailor studies to patients most likely to have the greatest treatment response.

Indexed as

Hypertension, PulmonaryPulmonary Arterial HypertensionAntihypertensive AgentsFamilial Primary Pulmonary HypertensionHumansTreatment OutcomeAntihypertensive Agents

Identifiers

PMID37169384
PMCPMC10919241
OpenAlexW4376134833

What OpenQuestion holds

Textmetadata
LicenceTDM
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.