Evidence map›Paper›PMID 40847484›Full record

SynthesisJournal of the American Heart Association2025

Ticagrelor Paradox: Systematic Review and Network Meta-Analysis.

Atsuyuki Watanabe, Tadao Aikawa, Yoshihisa Miyamoto, Hiroki A Ueyama, Tomohiro Fujisaki, Satoshi Shoji, Kaveh Hosseini, Leandro Slipczuk, Alexandros Briasoulis, Polydoros N Kampaktsis and 5 more

Abstract readSystematic ReviewNetwork Meta-Analysis
In one paragraph

Synthesis in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Atsuyuki WatanabeDepartment of Medicine, Mount Sinai Morningside and West Icahn School of Medicine at Mount Sinai New York NY USA.ORCID 0000-0001-8781-0329
Tadao AikawaDepartment of Cardiovascular Biology and Medicine Juntendo University Graduate School of Medicine Tokyo Japan.ORCID 0000-0002-1786-0176
Yoshihisa MiyamotoDepartment of Real-World Evidence, Graduate School of Medicine University of Tokyo Bunkyo City Japan.ORCID 0000-0003-2852-2946
Hiroki A UeyamaDivision of Cardiology Emory University School of Medicine Atlanta GA USA.
Tomohiro FujisakiDepartment of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka Japan.ORCID 0000-0001-9204-8551
Satoshi ShojiDuke Clinical Research Institute Durham NC USA.ORCID 0000-0002-2223-7215
Kaveh HosseiniTehran Heart Center, Cardiovascular Diseases Research Institute Tehran University of Medical Sciences Tehran Iran.ORCID 0000-0001-5676-3099
Leandro SlipczukCardiology Division Montefiore Medical Center/Albert Einstein College of Medicine Bronx NY USA.ORCID 0000-0003-3091-3735
Alexandros BriasoulisSection of Heart Failure University of Iowa Iowa City IA USA.ORCID 0000-0002-5740-9670
Polydoros N KampaktsisStructural and Congenital Center Hackensack University Medical Center Hackensack NJ USA.
Jose WileySection of Cardiology, Department of Medicine Tulane University School of Medicine New Orleans LA USA.ORCID 0000-0002-9940-0367
Eric A SecemskyDivision of Cardiology Beth Israel Deaconess Medical Center Boston MA USA.ORCID 0000-0003-3861-3163
Masao IwagamiDepartment of Digital Health, Institute of Medicine University of Tsukuba Tsukuba Japan.ORCID 0000-0001-7079-0640
Yusuke TsugawaDivision of General Internal Medicine and Health Services Research David Geffen School of Medicine at UCLA Los Angeles CA USA.ORCID 0000-0002-1937-4833
Toshiki KunoDivision of Cardiology Beth Israel Deaconess Medical Center Boston MA USA.ORCID 0000-0002-2487-8366

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBased on the landmark PLATO (Platelet Inhibition and Patient Outcomes) and TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction) trials, current guidelines recommend ticagrelor and prasugrel over clopidogrel for acute coronary syndrome. However, subsequent studies have failed to replicate the reported benefits of ticagrelor, raising concerns about the validity of the PLATO trial's findings.

methodsRandomized trials published until January 2025 were searched on PubMed and Embase and included if they compared 2 of the 3 standard dual antiplatelet therapies: 12 months aspirin plus clopidogrel, prasugrel, or ticagrelor. We constructed a network with and without PLATO to assess its impact on the synthesized risk estimates on major adverse cardiovascular events, patient mortality, myocardial infarction, and stent thrombosis, as well as major bleeding and major or minor bleeding.

resultsTwelve trials, enrolling 52 415 patients (clopidogrel: 23 557; ticagrelor: 13 344, prasugrel: 15 514) were included. The analysis with PLATO showed lower hazard ratios for ticagrelor versus clopidogrel than the analysis without PLATO in major adverse cardiovascular events, mortality, myocardial infarction, and bleeding outcomes (e.g., cardiovascular mortality; hazard ratio [HR], 0.83 [95% CI, 0.72-0.96] when PLATO was included; HR, 0.96 [95% CI, 0.73-1.25] when PLATO was excluded). Ticagrelor and prasugrel were associated with higher incidences of major bleeding and major or minor bleeding for analyses including and excluding PLATO, altohugh the point estimates for ticagrelor were lower when PLATO was included.

conclusionsThe pooled estimates with PLATO favored ticagrelor compared with estimates without PLATO in several studied outcomes, potentially suggesting the substantial impacts of PLATO's findings on the pooled risk estimates; therefore, additional evidence may be needed given the large number of patients worldwide treated with dual antiplatelet therapy.

Indexed as

Acute Coronary SyndromePlatelet Aggregation InhibitorsTicagrelorClopidogrelHemorrhageHumansPrasugrel HydrochlorideRandomized Controlled Trials as TopicTreatment OutcomeClopidogrelPlatelet Aggregation InhibitorsPrasugrel HydrochlorideTicagreloracute coronary syndromeclinical trialdual antiplatelet therapyguideline

Identifiers

PMID40847484
PMCPMC12553455

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.