Evidence mapPaperPMID 36100672Full record

Trial reportHypertension research : official journal of the Japanese Society of Hypertension2023

The renoprotective effect of esaxerenone independent of blood pressure lowering: a post hoc mediation analysis of the ESAX-DN trial.

Yasuyuki Okuda, Sadayoshi Ito, Naoki Kashihara, Kenichi Shikata, Masaomi Nangaku, Takashi Wada, Tomoko Sawanobori, Masataka Taguri

Open access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in Hypertension research : official journal of the Japanese Society of Hypertension, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. 2023 update and perspectives.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 7 institutions in 1 country.

Yasuyuki OkudaData Intelligence Department, Daiichi Sankyo Co., Ltd, Tokyo, Japan. okuda.yasuyuki.ec@daiichisankyo.co.jp.
Sadayoshi ItoDivision of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University School of Medicine, Sendai, Japan.
Naoki KashiharaDepartment of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.
Kenichi ShikataCenter for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
Masaomi NangakuDivision of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takashi WadaDepartment of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan.
Tomoko SawanoboriClinical Development Department I, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Masataka TaguriDepartment of Health Data Science, Tokyo Medical University, Tokyo, Japan.
Daiichi-Sankyo (Japan) · JPKanazawa University · JPKawasaki Medical School · JPOkayama University Hospital · JPThe University of Tokyo · JPTohoku University · JPTokyo Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are recommended as first-line drugs for hypertension with diabetic nephropathy owing to their renoprotective effect; however, their effect beyond lowering blood pressure (BP) has not been confirmed. Recent studies have shown that aldosterone plays a key role in causing renal injury; therefore, it is likely that mineralocorticoid receptor (MR) blockers inhibit aldosterone-induced renal damage in different ways from ACE inhibitors and ARBs. Therefore, we investigated the mechanism of the effect of an MR blocker on reducing the urinary albumin-to-creatinine ratio (UACR) using data from a randomized, double-blind, placebo-controlled phase 3 study (ESAX-DN) of a new nonsteroidal MR blocker, esaxerenone. This post hoc analysis used a novel statistical method to quantitatively estimate the effect of esaxerenone on UACR reduction mediated, or not mediated, by changes in systolic BP (SBP) and/or estimated glomerular filtration rate (eGFR). The proportion of the mediated effect by SBP changes to the total effect on UACR reduction was 9.8-10.7%; the UACR was reduced to 0.903-0.911 times the baseline at the end of treatment through the SBP-related pathway and to 0.422-0.426 times the baseline through the non-SBP-related pathway. Even considering both SBP and eGFR simultaneously, the proportion of the mediated effect was 21.9-28.1%. These results confirm that esaxerenone has a direct UACR-lowering effect independent of BP lowering and that its magnitude is much larger than that of the BP-dependent effect. Thus, esaxerenone could be a UACR-reducing treatment option for patients with diabetic nephropathy.

Indexed as

Diabetic NephropathiesHypertensionAldosteroneAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsAntihypertensive AgentsBlood PressureHumansMediation AnalysisMineralocorticoid Receptor AntagonistsPyrrolesSulfonesAldosteroneAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsAntihypertensive AgentsesaxerenoneMineralocorticoid Receptor AntagonistsPyrrolesSulfonesBlood pressureDiabetic nephropathyEsaxerenoneHypertensionMediation analysis

Identifiers

PMID36100672
PMCPMC9899688
OpenAlexW4295413087

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.