Evidence map›Paper›PMID 28032893›Full record

ArticleClinical pharmacology and therapeutics2017

Anticoagulation endpoints with clinical implementation of warfarin pharmacogenetic dosing in a real-world setting: A proposal for a new pharmacogenetic dosing approach.

M J Arwood, J Deng, K Drozda, O Pugach, E A Nutescu, S Schmidt, J D Duarte, L H Cavallari

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 5% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Cardiovascular precision medicine - A pharmacogenomic perspective.Cambridge prisms. Precision medicine · 2023
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Polymorphisms ofThe application of clinical genetics · 2019
    Article
  14. Article
  15. Article
  16. Review
  17. Pharmacogenetic Implementation Lessons From the "Real World".Clinical pharmacology and therapeutics · 2017
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

M J ArwoodDepartment of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida, USA.
J DengCenter for Pharmacometrics and Systems Pharmacology, University of Florida at Lake Nona, Orlando, Florida, USA.
K DrozdaGenomics and Targeted Therapy, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland, USA.
O PugachInstitute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois, USA.
E A NutescuPersonalized Medicine Program, University of Illinois at Chicago, Chicago, Illinois, USA.
S SchmidtCenter for Pharmacometrics and Systems Pharmacology, University of Florida at Lake Nona, Orlando, Florida, USA.
J D DuarteDepartment of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida, USA.
L H CavallariDepartment of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida, USA.
University of Florida · USUniversity of Illinois Chicago · USTarget (United States) · US

Funding

Improving treatment personalization for pulmonary hypertension associated with diastolic heart failureK23GM112014 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DUARTE, JULIO DAVID · 2015 to 2018
$711k
Patient-Centered Anticoagulation Self-Monitoring in Minority Patients.K23HL112908 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI NUTESCU, EDITH · 2013 to 2016
$524k
NHLBI NIH HHS K23 HL112908NIGMS NIH HHS K23 GM112014
6 · The paper itself

Abstract

Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype-guided warfarin dosing, we aimed to examine genotype-associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced-function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7.8 ± 5.8, 7.2 ± 4.7, and 5.4 ± 4.6 days, P = 0.0004) and mean percentage of time in therapeutic range in the first 28 days (22.2, 27.8, and 32.2%, P = 0.0127) with use of existing pharmacogenetic algorithms. These data suggest that more aggressive dosing is necessary for patients with 0 to 1 VKORC1/CYP2C9 variants to more efficiently achieve therapeutic anticoagulation. Herein, we provide a novel kinetic/pharmacodynamic-derived dosing nomogram optimized for a heterogeneous patient population.

Indexed as

PharmacogeneticsAlgorithmsAllelesAnticoagulantsCytochrome P-450 CYP2C9Dose-Response Relationship, DrugEndpoint DeterminationFemaleGenotypeHumansMaleMiddle AgedVitamin K Epoxide ReductasesWarfarinAnticoagulantsCYP2C9 protein, humanCytochrome P-450 CYP2C9Vitamin K Epoxide ReductasesVKORC1 protein, humanWarfarin

Identifiers

PMID28032893
PMCPMC5395307
OpenAlexW2548537342

What OpenQuestion holds

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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.