Evidence map›Paper›PMID 29237680›Full record

ArticleCirculation. Cardiovascular genetics2017

Personalized Anticoagulation: Optimizing Warfarin Management Using Genetics and Simulated Clinical Trials.

Kourosh Ravvaz, John A Weissert, Christian T Ruff, Chih-Lin Chi, Peter J Tonellato

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Cardiovascular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Kourosh RavvazFrom the Aurora Research Institute, Aurora Health Care, Milwaukee, WI (K.R., J.A.W.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.T.R., P.J.T.); School of Nursing and Institute for Health Informatics, University of Minnesota, Minneapolis (C.-L.C.); and University of Wisconsin, Milwaukee (P.J.T.). kourosh.ravvaz@aurora.org.
John A WeissertFrom the Aurora Research Institute, Aurora Health Care, Milwaukee, WI (K.R., J.A.W.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.T.R., P.J.T.); School of Nursing and Institute for Health Informatics, University of Minnesota, Minneapolis (C.-L.C.); and University of Wisconsin, Milwaukee (P.J.T.).
Christian T RuffFrom the Aurora Research Institute, Aurora Health Care, Milwaukee, WI (K.R., J.A.W.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.T.R., P.J.T.); School of Nursing and Institute for Health Informatics, University of Minnesota, Minneapolis (C.-L.C.); and University of Wisconsin, Milwaukee (P.J.T.).
Chih-Lin ChiFrom the Aurora Research Institute, Aurora Health Care, Milwaukee, WI (K.R., J.A.W.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.T.R., P.J.T.); School of Nursing and Institute for Health Informatics, University of Minnesota, Minneapolis (C.-L.C.); and University of Wisconsin, Milwaukee (P.J.T.).
Peter J TonellatoFrom the Aurora Research Institute, Aurora Health Care, Milwaukee, WI (K.R., J.A.W.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.T.R., P.J.T.); School of Nursing and Institute for Health Informatics, University of Minnesota, Minneapolis (C.-L.C.); and University of Wisconsin, Milwaukee (P.J.T.).

Funding

PREDICTIVE OPTIMAL ANTICLOTTING TREATMENT FOR SEGMENTED PATIENT POPULATIONSR01LM011566 · NLM · UNIVERSITY OF MISSOURI-COLUMBIA · PI TONELLATO, PETER J. · 2013 to 2016
$1.0M
NLM NIH HHS R01 LM011566
6 · The paper itself

Abstract

backgroundClinical trials testing pharmacogenomic-guided warfarin dosing for patients with atrial fibrillation have demonstrated conflicting results. Non-vitamin K antagonist oral anticoagulants are expensive and contraindicated for several conditions. A strategy optimizing anticoagulant selection remains an unmet clinical need. METHODS AND

resultsCharacteristics from 14 206 patients with atrial fibrillation were integrated into a validated warfarin clinical trial simulation framework using iterative Bayesian network modeling and a pharmacokinetic-pharmacodynamic model. Individual dose-response for patients was simulated for 5 warfarin protocols-a fixed-dose protocol, a clinically guided protocol, and 3 increasingly complex pharmacogenomic-guided protocols. For each protocol, a complexity score was calculated using the variables predicting warfarin dose and the number of predefined international normalized ratio (INR) thresholds for each adjusted dose. Study outcomes included optimal time in therapeutic range ≥65% and clinical events. A combination of age and genotype identified different optimal protocols for various subpopulations. A fixed-dose protocol provided well-controlled INR only in normal responders ≥65, whereas for normal responders <65 years old, a clinically guided protocol was necessary to achieve well-controlled INR. Sensitive responders ≥65 and <65 and highly sensitive responders ≥65 years old required pharmacogenomic-guided protocols to achieve well-controlled INR. However, highly sensitive responders <65 years old did not achieve well-controlled INR and had higher associated clinical events rates than other subpopulations.

conclusionsUnder the assumptions of this simulation, patients with atrial fibrillation can be triaged to an optimal warfarin therapy protocol by age and genotype. Clinicians should consider alternative anticoagulation therapy for patients with suboptimal outcomes under any warfarin protocol.

Indexed as

AgedAged, 80 and overAnticoagulantsAtrial FibrillationBayes TheoremClinical Trials as TopicComputer SimulationFemaleGenotypeHumansInternational Normalized RatioMaleMiddle AgedOutcome Assessment, Health CarePharmacogeneticsPrecision MedicineAnticoagulantsWarfarinanticoagulantsatrial fibrillationcomputer simulationgenotypepharmacogeneticswarfarin

Identifiers

PMID29237680
PMCPMC5734112

What OpenQuestion holds

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Registered trials

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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.