Evidence map›Paper›PMID 34014506›Full record

ArticleDrug safety2021

Risk of Severe Abnormal Uterine Bleeding Associated with Rivaroxaban Compared with Apixaban, Dabigatran and Warfarin.

Efe Eworuke, Laura Hou, Rongmei Zhang, Hui-Lee Wong, Peter Waldron, Abby Anderson, Audrey Gassman, David Moeny, Ting-Ying Huang

Abstract read
PubMed Publisher
In one paragraph

Article in Drug safety, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Innovations in pharmacovigilance studies of medicines in older people.British journal of clinical pharmacology · 2025
    Review
  6. 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

9 authors at 4 institutions in 1 country.

Efe EworukeDivision of Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA. Efe.Eworuke@fda.hhs.gov.ORCID 0000-0001-8971-9748
Laura HouDepartment of Population Medicine, Harvard Medical School, Harvard Pilgrim Health+ Care Institute, Boston, MA, USA.
Rongmei ZhangDivision of Biometrics, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Hui-Lee WongCenter for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Peter WaldronDivision of Pharmacovigilance, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Abby AndersonDivision of Urology, Obstetrics and Gynecology, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Audrey GassmanDivision of Urology, Obstetrics and Gynecology, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
David MoenyDivision of Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Ting-Ying HuangDepartment of Population Medicine, Harvard Medical School, Harvard Pilgrim Health+ Care Institute, Boston, MA, USA.
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · USHarvard University · USCenter for Biologics Evaluation and Research · US

Funding

FDA HHS HHSF223200910006I
6 · The paper itself

Abstract

introductionThere have been reports of clinically relevant uterine bleeding events among women of reproductive age exposed to rivaroxaban.

objectiveThe aim of this study was to compare the risk of severe abnormal uterine bleeding (SAUB) resulting in transfusion or surgical intervention among women on rivaroxaban versus apixaban, dabigatran and warfarin.

methodsWe conducted a retrospective cohort study in the FDA's Sentinel System (10/2010-09/2015) among females aged 18+ years with venous thromboembolism (VTE), or atrial flutter/fibrillation (AF) who newly initiated a direct oral anticoagulant (DOAC; rivaroxaban, apixaban, dabigatran) or warfarin. We followed women from dispensing date until the earliest of transfusion or surgery following vaginal bleeding, disenrollment, exposure or study end date, or recorded death. We estimated hazard ratios (HRs) using Cox proportional hazards regression via propensity score stratification. Four pairwise comparisons were conducted for each intervention.

resultsOverall, there was an increased risk of surgical intervention with rivaroxaban when compared with dabigatran (HR 1.19; 95% CI 1.03-1.38), apixaban (1.23; 1.04-1.47), and warfarin (1.34; 1.22-1.47). No difference in risk for surgical intervention was observed for dabigatran-apixaban comparisons. Increased risk of transfusion was observed for rivaroxaban compared with dabigatran (1.49; 1.03-2.17) only. For patients with no gynecological history, rivaroxaban was associated with risk of surgical intervention compared with dabigatran (1.22; 1.05-1.42), apixaban (1.25; 1.04-1.49), and warfarin (1.36; 1.23-1.50).

conclusionOur study found increased SAUB risk with rivaroxaban use compared with other DOACs or warfarin. Increased risk with rivaroxaban was present among women without underlying gynecological conditions. Women on anticoagulant therapy should be aware of a risk of SAUB.

Indexed as

Atrial FibrillationStrokeAnticoagulantsDabigatranFemaleHumansPyrazolesPyridonesRetrospective StudiesRivaroxabanUterine HemorrhageWarfarinAnticoagulantsapixabanDabigatranPyrazolesPyridonesRivaroxabanWarfarin

Identifiers

PMID34014506
OpenAlexW3162897546

What OpenQuestion holds

Textmetadata
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.