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ArticleOpen heart

Time-based measures of treatment effect: reassessment of ticagrelor and clopidogrel from the PLATO trial.

Andrea Bellavia, Lars Wallentin, Nicola Orsini, Stefan K James, Christopher P Cannon, Anders Himmelmann, Johan Sundström, Henrik Renlund, Per Lytsy

Registry-linked trialAbstract read
In one paragraph

Article in Open heart. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00391872 (A Randomised, Double-blind, Parallel Group, Phase 3, Efficacy and Safety Study of Ticagrelor Compared With Clopidogrel for Prevention of Vascular Events in Patients With Non-ST or ST Elevation Acute Coronary Syndromes), which is not on this map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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.

NCT00391872 phase3completednot on this map

A Randomised, Double-blind, Parallel Group, Phase 3, Efficacy and Safety Study of Ticagrelor Compared With Clopidogrel for Prevention of Vascular Events in Patients With Non-ST or ST Elevation Acute Coronary Syndromes (ACS) [PLATO- a Study of PLATelet Inhibition and Patient Outcomes]

TypeinterventionalSponsorAstraZenecaRan2006 to 2009Enrolled18,624ConditionsAcute Coronary SyndromeArmsTicagrelor, Clopidogrel
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Antiplatelet agents for chronic kidney disease.The Cochrane database of systematic reviews · 2022
    Pooled it
  2. Trial
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.

Andrea BellaviaInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Lars WallentinDepartment of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
Nicola OrsiniDepartment of Public Health Science, Karolinska Institutet, Stockholm, Sweden.
Stefan K JamesDepartment of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
Christopher P CannonDivision of Cardiovascular, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Anders HimmelmannAstraZeneca Research and Development, Gothenburg, Sweden.
Johan SundströmDepartment of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
Henrik RenlundUppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Per LytsyDepartment of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTreatment effects to binary endpoints using time-to-event data in randomised controlled trials are typically summarised by reporting HRs derived with Cox proportional hazard models. Alternative and complementary methods include summarising the between-treatment differences on the metric time scale, quantifying the effect as delay of the event (DoE). The aim of this study was to reassess data from the PLATO study expressing the effects as the time by which the main outcomes are delayed or hastened due to treatment.

methodsPLATO was a randomised controlled double-blind multicentre study (n=18,624), conducted between 2006 and 2008, which demonstrated superiority of the antiplatelet treatment ticagrelor over clopidogrel in reducing risk of several cardiovascular events. In the present study, four of the main PLATO outcomes were reassessed by calculating the time by which an event may be delayed due to the treatment.

resultsThe effects of ticagrelor, as compared with clopidogrel, consisted of a substantial delay of the evaluated outcomes, ranging from 83 to 98 days over 400-day follow-up. The Delay of Events Curves showed that the effects progressively increased over time, and the significant findings were concordant with those presented in the original PLATO study.

conclusionsThis study confirmed evidence of a beneficial effect of ticagrelor over clopidogrel, and provided the magnitude of such effects in terms of delayed event time. Investigating time-to-event data with a percentile approach allows presenting treatment effects from randomised controlled studies as absolute measures of the time by which an event may be delayed due to the treatment. TRIAL REGISTRATION NUMBER: PLATO (www.clinicaltrials.gov; NCT00391872); Results.

Indexed as

acute coronary syndromeanticoagulationclinical trials

Identifiers

PMID28761675
PMCPMC5515127

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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.