Evidence map›Paper›PMID 35997941›Full record

SynthesisDrugs2022

Antithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis.

Loes H Willems, Dominique P M S M Maas, Kees Kramers, Michel M P J Reijnen, Niels P Riksen, Hugo Ten Cate, Rozemarijn J van der Vijver-Coppen, Gert J de Borst, Barend M E Mees, Clark J Zeebregts and 2 more

Erratum issuedOpen access · hybridAbstract readSystematic ReviewNetwork Meta-Analysis
In one paragraph

Synthesis in Drugs, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 3 pooled it
6.5field-weighted citation impact, top 2% 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

10 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Risk of bleeding with concomitant use of oral anticoagulants and aspirin: A systematic review and meta-analysis.American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists · 2024
    Pooled it
  4. Article
  5. Article
  6. Review
  7. The Impact of Single Nucleotide Polymorphisms and Other Mechanisms on Aspirin Resistance.Cardiovascular & hematological disorders drug targets · 2025
    Review
  8. Article
  9. Review
  10. Integrating Mechanisms in Thrombotic Peripheral Arterial Disease.Pharmaceuticals (Basel, Switzerland) · 2022
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Loes H WillemsDepartment of Surgery, Radboud University Medical Center, Postbus 9101 (Intern 618), 6500 HB, Nijmegen, The Netherlands. Loes.h.willems@radboudumc.nl.ORCID http://orcid.org/0000-0002-2728-9663
Dominique P M S M MaasDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Kees KramersDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Michel M P J ReijnenDepartment of Surgery, Rijnstate Hospital, Arnhem, and Multi-Modality Medical Imaging Group, University of Twente, Enschede, The Netherlands.
Niels P RiksenDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Hugo Ten CateDepartments of Internal Medicine and Biochemistry, Maastricht University Medical Center and CARIM School for Cardiovascular diseases, Maastricht, The Netherlands.
Rozemarijn J van der Vijver-CoppenDepartment of Surgery, Radboud University Medical Center, Postbus 9101 (Intern 618), 6500 HB, Nijmegen, The Netherlands.
Gert J de BorstDepartment of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Barend M E MeesDepartment of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.
Clark J ZeebregtsDepartment of Surgery (Division of Vascular Surgery), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gerjon HanninkDepartment of Operating Rooms, Radboud University Medical Center, Nijmegen, The Netherlands.
Michiel C WarléDepartment of Surgery, Radboud University Medical Center, Postbus 9101 (Intern 618), 6500 HB, Nijmegen, The Netherlands.
Radboud University Nijmegen · NLJohannes Gutenberg University Mainz · DEMaastricht University · NLRijnstate Hospital · NLUniversity Medical Center Groningen · NLUniversity Medical Center Utrecht · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.

methodsA systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.

resultsTwenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.

conclusionClopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.

Indexed as

Fibrinolytic AgentsPeripheral Arterial DiseaseAspirinClopidogrelHemorrhageHumansPlatelet Aggregation InhibitorsRivaroxabanTicagrelorVitamin KAspirinClopidogrelFibrinolytic AgentsPlatelet Aggregation InhibitorsRivaroxabanTicagrelorVitamin K

Identifiers

PMID35997941
PMCPMC9499921
OpenAlexW4292702794

What OpenQuestion holds

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LicenceCC BY-NC
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.