Evidence map›Paper›PMID 35997730›Full record

Trial reportJAMA2022

Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial.

CRISTAL Study Group, Verinder S Sidhu, Thu-Lan Kelly, Nicole Pratt, Stephen E Graves, Rachelle Buchbinder, Sam Adie, Kara Cashman, Ilana Ackerman, Durga Bastiras and 37 more

2 registry-linked trialsOpen access · bronzeAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JAMA, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 67 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 4 pooled it
34.4field-weighted citation impact, top 1% 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.

NCT06611319 phase3recruitingnot on this mapstarted 2024, after this paper: background citation

ENhanced Recovery and ABbreviated LEngth of Anticoagulation for Thromboprophylaxis After Primary Hip Arthroplasty

TypeinterventionalSponsorProf. Stavros Konstantinides, MDRan2024 to 2027Enrolled2,932ConditionsHip Arthroplasty, Total, Prevention of Venous ThromboembolismArmsPrevention of Venous Thromboembolism, Placebo Oral Tablet
NCT07506473 nanot yet recruitingnot on this mapstarted 2026, after this paper: background citation

Intermediate Versus Standard Dose Enoxaparin to Prevent Venous Thromboembolism in Severe Trauma Patients: a Multicenter Double Blind Randomised Controlled Trial

TypeinterventionalSponsorUniversity Hospital, GrenobleRan2026 to 2028Enrolled540ConditionsSevere Trauma Patient, Venous ThromboembolismArmsEnoxaparin standard dose, Enoxaparin intermediate dose
3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 4 syntheses or guidelines pooled it, 167 citations in OpenAlex.

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  5. Efficacy of Atorvastatin Against Venous Thromboembolism After Total Hip Arthroplasty.Journal of musculoskeletal & neuronal interactions · 2025
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  13. The bleeding risk of low-molecular-weight heparin bridging therapy in patients receiving preoperative oral antithrombotic drugs during spinal fusion surgery.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

47 authors at 20 institutions in 1 country.

CRISTAL Study Group
Verinder S SidhuSchool of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Thu-Lan KellyClinical and Health Sciences, Quality Use of Medicines Pharmacy Research Centre, University of South Australia, Adelaide, South Australia, Australia.
Nicole PrattClinical and Health Sciences, Quality Use of Medicines Pharmacy Research Centre, University of South Australia, Adelaide, South Australia, Australia.
Stephen E GravesAustralian Orthopaedic Association National Joint Replacement Registry, Adelaide, South Australia, Australia.
Rachelle BuchbinderDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Sam AdieSchool of Clinical Medicine, UNSW Medicine and Health, St George and Sutherland Clinical Campuses, Faculty of Medicine and Health, UNSW Sydney, New South Wales, Australia.
Kara CashmanSouth Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Ilana AckermanDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Durga BastirasAustralian Orthopaedic Association National Joint Replacement Registry, Adelaide, South Australia, Australia.
Roger BrightonOrthopaedic Department, Westmead Private Hospital, Westmead, Sydney, New South Wales, Australia.
Alexander W R BurnsOrthopaedic Department, Calvary John James Hospital, Deakin, Canberra, Australian Capital Territory, Australia.
Beng Hock ChongDepartment of Medicine, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Ornella ClavisiMusculoskeletal Australia, Melbourne, Victoria, Australia.
Maggie CrippsSchool of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Mark DekkersOrthopaedic Department, Greenslopes Private Hospital, Greenslopes, Brisbane, Queensland, Australia.
Richard de SteigerDepartment of Surgery, Epworth Healthcare, University of Melbourne, Melbourne, Victoria, Australia.
Michael DixonOrthopaedic Department, Kareena Private Hospital, Sutherland, Sydney, New South Wales, Australia.
Andrew EllisOrthopaedic Department, Royal North Shore Hospital, St Leonard's, Sydney, New South Wales, Australia.
Elizabeth C GriffithSouth Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
David HaleOrthopaedic Department, Hornsby and Kuringai Hospital, Hornsby, Sydney, New South Wales, Australia.
Amber HansenSchool of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Anthony HarrisCentre for Health Economics, Monash Business School, Monash University, Melbourne, Victoria, Australia.
Raphael HauDepartment of Surgery, Epworth Healthcare, University of Melbourne, Melbourne, Victoria, Australia.
Mark HorsleyOrthopaedic Department, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia.
Dugal JamesBendigo Healthcare Group, Bendigo Hospital, Bendigo, Victoria, Australia.
Omar KhorshidOrthopaedic Department, Fremantle Hospital, Fremantle, Western Australia, Australia.
Leonard KuoOrthopaedic Department, Canterbury Hospital, Canterbury, Sydney, New South Wales, Australia.
Peter LewisOrthopaedic Department, Calvary Hospital, Adelaide, South Australia, Australia.
David LieuOrthopaedic Department, Fairfield Hospital, Fairfield, Sydney, New South Wales, Australia.
Michelle LorimerSouth Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Samuel MacDessiSchool of Clinical Medicine, UNSW Medicine and Health, St George and Sutherland Clinical Campuses, Faculty of Medicine and Health, UNSW Sydney, New South Wales, Australia.
Peter McCombeOrthopaedic Department, Frankston Hospital, Frankston, Melbourne, Victoria, Australia.
Catherine McDougallOrthopaedic Department, The Prince Charles Hospital, Chermside, Brisbane, Queensland, Australia.
Jonathan MulfordOrthopaedic Department, Launceston General Hospital, Launceston, Tasmania, Australia.
Justine Maree NaylorSchool of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Richard S PageSchool of Medicine, St John of God Hospital and Barwon Health, Deakin University, Geelong, Victoria, Australia.
John RadovanovicOrthopaedic Department, Mater Hospital, Raymond Terrace, Brisbane, Queensland, Australia.
Michael SolomonOrthopaedic Department, Prince of Wales Hospital, Randwick, Sydney, New South Wales, Australia.
Rami SorialOrthopaedic Department, Nepean Hospital, Nepean, Sydney, New South Wales, Australia.
Peter SummersellOrthopaedic Department, Coffs Harbour Base Hospital, Coffs Harbour, New South Wales, Australia.
Phong TranOrthopaedic Department, Western Health, Melbourne, Victoria, Australia.
William L WalterOrthopaedic Department, Royal North Shore Hospital, St Leonard's, Sydney, New South Wales, Australia.
Steve WebbDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Chris WilsonOrthopaedic Department, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, Australia.
David WysockiOrthopaedic Department, Sir Charles Gardiner Hospital, Perth, Western Australia, Australia.
Ian A HarrisSchool of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
UNSW Sydney · AUThe University of Sydney · AUThe University of Melbourne · AUUniversity of South Australia · AUAustralian Orthopaedic Association · AUCanterbury Hospital · AUFairfield Hospital · AUFlinders University · AUFrankston Hospital · AUHornsby Ku-ring-gai Hospital · AULaunceston General Hospital · AUMater Health Services · AUNepean Hospital · AUWestmead Hospital · AUBarwon Health · AUCabrini Hospital · AUCoffs Harbour City Council · AUFremantle Hospital · AUGreenslopes Private Hospital · AURoyal Prince Alfred Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Objective: To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA. Design, Setting, and Participants: Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021. Interventions: Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation. Main Outcomes and Measures: The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group. Results: Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group. Conclusions and Relevance: Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis. Trial Registration: ANZCTR Identifier: ACTRN12618001879257.

Indexed as

AnticoagulantsArthroplasty, Replacement, HipArthroplasty, Replacement, KneeAspirinEnoxaparinVenous ThromboembolismAgedAustraliaChemopreventionFemaleHumansMaleOsteoarthritisPostoperative ComplicationsPulmonary EmbolismAnticoagulantsAspirinEnoxaparin

Identifiers

PMID35997730
PMCPMC9399863
OpenAlexW4292840770

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.