Evidence map›Paper›PMID 35677694›Full record

ArticleFrontiers in cardiovascular medicine2022

Comparative Risks of Fracture Among Direct Oral Anticoagulants and Warfarin: A Systematic Review and Network Meta-Analysis.

Sung Huang Laurent Tsai, Ching-Wei Hu, Shih-Chieh Shao, Eric H Tischler, Olufunmilayo H Obisesan, Dominique Vervoort, Wei Cheng Chen, Jiun-Ruey Hu, Liang-Tseng Kuo

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cardiovascular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Observational
  4. Drug-Induced Osteoporosis.Journal of clinical medicine · 2026
    Review
  5. Article
  6. Review
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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 6 institutions in 2 countries.

Sung Huang Laurent TsaiDepartment of Orthopaedic Surgery, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan.
Ching-Wei HuDepartment of Orthopaedic Surgery, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan.
Shih-Chieh ShaoDepartment of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan.
Eric H TischlerDepartment of Orthopaedic Surgery and Rehabilitation Medicine, Downstate Medical Center, State University of New York, New York, NY, United States.
Olufunmilayo H ObisesanJohns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Dominique VervoortJohns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Wei Cheng ChenSchool of Medicine, Chang Gung University, Taoyuan, Taiwan.
Jiun-Ruey HuDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Liang-Tseng KuoSchool of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chang Gung University · TWJohns Hopkins University · USKeelung Chang Gung Memorial Hospital · TWChang Gung Memorial Hospital · TWSUNY Downstate Health Sciences University · USVanderbilt University Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Previous studies have shown the effectiveness and safety of direct oral anticoagulants (DOACs), including lower fracture risks, compared to warfarin. However, direct or indirect comparisons between different DOACs are scarce in the literature. Objective: This study aims to compare fracture risks among different DOACs and warfarin, including apixaban, rivaroxaban, dabigatran, and edoxaban, in patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Methods: We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science for randomized controlled trials and cohort studies comparing the fracture risks among patients who used warfarin or DOACs, up to March 2021. Two authors extracted data and appraised the risk of bias of included studies. The primary outcome was fracture risk. We performed pairwise meta-analyses to compare differences between medications and network meta-analyses using frequentist random-effects models to compare through indirect evidence. We used surface under the cumulative ranking curve (SUCRA) and mean ranks to determine the probability of a DOAC ranking best in terms of fracture risk. Results: Thirty-one studies were included in the final analysis. Twenty-four randomized controlled trials and seven cohort studies with 455,343 patients were included in the systematic review and network meta-analysis. Compared to warfarin, the risk of any fractures was lowest with apixaban [relative risk (RR) = 0.59; 95% confidence interval (CI): 0.48-0.73], followed by rivaroxaban (RR: 0.72; 95% CI: 0.60-0.86), edoxaban (RR: 0.88; 95% CI: 0.62-1.23), and dabigatran (RR = 0.90; 95% CI: 0.75-1.07). No substantial inconsistency between direct and indirect evidence was detected for all outcomes. Conclusions: All DOACs were safer than warfarin concerning the risk of fracture; however, apixaban had the lowest relative risk of fracture within the class of DOACs. Further head-to-head prospective studies should confirm the comparative safety profiles of DOACs regarding fractures.

Indexed as

atrial fibrillationdirect-acting oral anticoagulant (DOAC)fracturenetwork meta-analysisnon-vitamin K antagonist oral anticoagulantsosteoporosisvenous thromboembolismwarfarin

Identifiers

PMID35677694
PMCPMC9168033
OpenAlexW4281286515

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Registered trials

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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.