Evidence map›Paper›PMID 35648242›Full record

Trial reportCardiovascular drugs and therapy2023

C-reactive Protein Levels and Cardiovascular Outcomes After Febuxostat Treatment in Patients with Asymptomatic Hyperuricemia: Post-hoc Analysis of a Randomized Controlled Study.

Sunao Kojima, Kazuaki Uchiyama, Naoto Yokota, Eiichi Tokutake, Yutaka Wakasa, Shinya Hiramitsu, Masako Waki, Hideaki Jinnouchi, Hirokazu Kakuda, Takahiro Hayashi and 11 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Cardiovascular drugs and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01984749 (A Multicenter, Randomized, Comparative Trial on the Effect of Febuxostat in Preventing Cerebral and Cardiorenovascular Events in Patients With Hyperuricemia), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 36% 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.

NCT01984749 naunknown statusnot on this map

A Multicenter, Randomized, Comparative Trial on the Effect of Febuxostat in Preventing Cerebral and Cardiorenovascular Events in Patients With Hyperuricemia

TypeinterventionalSponsorFreed Study GroupRan2013Enrolled1,000ConditionsHyperuricemiaArmsFebuxostat
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
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

21 authors at 11 institutions in 1 country.

Sunao KojimaDepartment of Internal Medicine, Sakurajyuji Yatsushiro Rehabilitation Hospital, 2-4-33 Honmachi, Yatsushiro, 866-0861, Japan. kojimas@kumamoto-u.ac.jp.ORCID 0000-0002-1916-7252
Kazuaki UchiyamaUchiyama Clinic, 1161-1 Shita-machi, Yoshikawa-ku, Joetsu, 949-3443, Japan.
Naoto YokotaYokota Naika, 642-1 Komuta, Miyazaki, Hanagashima-cho, 880-0036, Japan.
Eiichi TokutakeTokutake Iin, 2-28-1 Asahi, Kawaguchi, 332-0001, Japan.
Yutaka WakasaWakasa Medical Clinic, 3-16-25 Sainen, Kanazawa, 920-0024, Japan.
Shinya HiramitsuHiramitsu Heart Clinic, 2-35 Shiroshita-cho, Minami-ku, Nagoya, 457-0047, Japan.
Masako WakiShizuoka City Shizuoka Hospital, 10-93 Ote-machi, Shizuoka, Aoi-ku, 420-8630, Japan.
Hideaki JinnouchiJinnouchi Hospital Diabetes Care Center, 6-2-3 Kuhonji, Kumamoto, Chuo-ku, 862-0976, Japan.
Hirokazu KakudaKakuda Iin, Na 15-1, Takamatsu, Kahoku, 929-1215, Japan.
Takahiro HayashiHayashi Medical Clinic, 5-22 Nakamozu-cho, Sakai, Kita-ku, 591-8023, Japan.
Naoki KawaiKawai Naika Clinic, 4-32 Kanazono-cho, Gifu, 500-8113, Japan.
Masahiro SugawaraSugawara Clinic, 3-9-16 Shakujii-machi, Nerima-ku, 177-0041, Japan.
Hisao MoriFuji Health Promotion Center, 392-5 Yunoki, Fuji, 416-0908, Japan.
Kenichi TsujitaDepartment of Cardiovascular Medicine, Kumamoto University, 1-1-1 Honjo, Kumamoto, Chuo-ku, 860-8556, Japan.
Kunihiko MatsuiDepartment of Family, Community, and General Medicine, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto, Chuo-ku, 860-8556, Japan.
Ichiro HisatomeInstitute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science, 86 Nishi-machi, Yonago, 683-8503, Japan.
Yusuke OhyaDepartment of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus School of Medicine 207 Uehara, Okinawa, Nishihara-cho, 903-0215, Japan.
Kazuo KimuraDivision of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-cho, Yokohama, Minami-ku, 232-0024, Japan.
Yoshihiko SaitoDepartment of Cardiovascular Medicine, Nara Medical University, 840 Shijyo-cho, Kashihara, 634-8522, Japan.
Hisao OgawaKumamoto University, 2-39-1 Kurokami, Kumamoto, Chuo-ku, 860-8555, Japan.
Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) investigators
Kumamoto University · JPHayashi Eye Hospital · JPKanazawa Medical Center · JPKumamoto University Hospital · JPNagoya Heart Center · JPNara Medical University · JPShizuoka City Hospital · JPTottori University · JPUji Hospital · JPUniversity of the Ryukyus · JPYokohama City University Medical Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeInflammation plays an important role in the initiation and progression of atherosclerosis, leading to poor clinical outcomes. Hyperuricemia is associated with the activation of the Nod-like receptor protein 3 inflammasome. Here, we investigated whether inhibition of inflammation using febuxostat lowered the risk of cardiovascular events.

methodsThis is a post-hoc analysis of the randomized trial, Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED). In total, 1067 patients (736 men and 331 women) were included in the analysis. We compared the serial changes in high-sensitivity C-reactive protein (hs-CRP) levels between febuxostat and non-febuxostat groups and assessed the correlation between the changes in uric acid (UA) and hs-CRP levels after febuxostat treatment. We also determined whether febuxostat could reduce a hard endpoint, defined as a composite of cardiovascular events and all-cause mortality.

resultsSerum UA levels in the febuxostat group were significantly lower than those in the non-febuxostat group after randomization (p < 0.05). However, hs-CRP levels were comparable between the two groups during the study. No significant correlation was observed between the changes in UA and hs-CRP levels after febuxostat treatment. The hard endpoints did not differ significantly between the two groups. In patients with baseline hs-CRP levels > 0.2 mg/dL or those administered 40 mg of febuxostat, the drug did not reduce hs-CRP levels or decrease the hard endpoint.

conclusionFebuxostat reduced the UA levels but did not affect the CRP levels, and therefore may fail to improve cardiovascular outcomes after treatment.

trial registrationClinicalTrial.gov (NCT01984749). https://clinicaltrials.gov/ct2/show/NCT01984749.

Indexed as

AtherosclerosisHyperuricemiaC-Reactive ProteinFebuxostatFemaleHumansInflammationMaleTreatment OutcomeUric AcidC-Reactive ProteinFebuxostatUric AcidCRPFebuxostatHyperuricemiaInflammationUric acidXOI

Identifiers

PMID35648242
OpenAlexW4281714164

What OpenQuestion holds

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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.