Evidence map›Paper›PMID 25736441›Full record

Trial reportJournal of the American Heart Association2015

Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial.

Daniel E Singer, Anne S Hellkamp, Zhong Yuan, Yuliya Lokhnygina, Manesh R Patel, Jonathan P Piccini, Graeme J Hankey, Günter Breithardt, Jonathan L Halperin, Richard C Becker and 6 more

Registry-linked trialOpen access · goldAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00403767 (A Prospective, Randomized, Double-Blind, Parallel-Group, Multicenter, Non-inferiority Study Comparing the Efficacy and Safety of Rivaroxaban), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 15% 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.

NCT00403767 phase3completednot on this map

A Prospective, Randomized, Double-Blind, Parallel-Group, Multicenter, Non-inferiority Study Comparing the Efficacy and Safety of Rivaroxaban (BAY 59-7939) With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Subjects With Non-Valvular Atrial Fibrillation

TypeinterventionalSponsorJohnson & Johnson Pharmaceutical Research & Development, L.L.C.Ran2006 to 2010Enrolled14,269ConditionsAtrial Fibrillation, Stroke, EmbolismArmsRivaroxaban, Warfarin, Matching placebo for Rivaroxaban arm (Warfarin placebo), Matching placebo for Warfarin arm (Rivaroxaban placebo)
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 16 citations in OpenAlex.

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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

16 authors at 11 institutions in 4 countries.

Daniel E SingerDivision of General Internal Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA (D.E.S.).
Anne S HellkampDuke Clinical Research Institute, Duke University Medical Center, Durham, NC (A.S.H., Y.L., M.R.P., J.P.P.).
Zhong YuanJanssen Pharmaceuticals, Raritan, NJ (Z.Y., C.C.N.).
Yuliya LokhnyginaDuke Clinical Research Institute, Duke University Medical Center, Durham, NC (A.S.H., Y.L., M.R.P., J.P.P.).
Manesh R PatelDuke Clinical Research Institute, Duke University Medical Center, Durham, NC (A.S.H., Y.L., M.R.P., J.P.P.).
Jonathan P PicciniDuke Clinical Research Institute, Duke University Medical Center, Durham, NC (A.S.H., Y.L., M.R.P., J.P.P.).
Graeme J HankeySchool of Medicine and Pharmacology, University of Western Australia, Crawley, Australia (G.J.H.).
Günter BreithardtDivision of Electrophysiology, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (B.).
Jonathan L HalperinMount Sinai Medical Center, The Cardiovascular Institute, New York, NY (J.L.H.).
Richard C BeckerDepartment of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH (R.C.B.).
Werner HackeRuprecht-Karls-University, Heidelberg, Germany (W.H.).
Christopher C NesselJanssen Pharmaceuticals, Raritan, NJ (Z.Y., C.C.N.).
Kenneth W MahaffeyDepartment of Medicine, Stanford University, Stanford, CA (K.W.M.).
Keith A A FoxUniversity of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, UK (K.A.F.).
Robert M CaliffDuke Translational Medicine Institute, Duke University Medical Center, Durham, NC (R.M.C.).
ROCKET AF Investigators
Clinical Research Institute · USDuke Medical Center · USJanssen (United States) · USEdinburgh Royal Infirmary · GBHarvard University · USHeidelberg University · DEMount Sinai Medical Center · USStanford University · USUniversity Hospital Münster · DEUniversity of Cincinnati Medical Center · USUniversity of Western Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. METHODS AND

resultsWe used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted.

conclusionsTTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported. CLINICAL

trial registrationURL: ClinicalTrials.gov. Unique identifier: NCT00403767.

Indexed as

Drug Dosage CalculationsInternational Normalized RatioAgedAnticoagulantsAsiaAtrial FibrillationBlood CoagulationDrug MonitoringEmbolismEuropeFemaleHumansLatin AmericaMaleNorth AmericaPredictive Value of TestsAnticoagulantsWarfarinanticoagulantsarrhythmiaembolismpreventionrisk factors

Identifiers

PMID25736441
PMCPMC4392426
OpenAlexW2145972504

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.