Projected Prevalence of Actionable Pharmacogenetic Variants and Level A Drugs Prescribed Among US Veterans Health Administration Pharmacy Users.


Journal

JAMA network open
ISSN: 2574-3805
Titre abrégé: JAMA Netw Open
Pays: United States
ID NLM: 101729235

Informations de publication

Date de publication:
05 06 2019
Historique:
entrez: 8 6 2019
pubmed: 8 6 2019
medline: 19 2 2020
Statut: epublish

Résumé

Implementation of pharmacogenetic testing to guide drug prescribing has potential to improve drug response and prevent adverse events. Robust data exist for more than 30 gene-drug pairs linking genotype to drug response phenotypes; however, it is unclear which pharmacogenetic tests, if implemented, would provide the greatest utility for a given patient population. To project the proportion of veterans in the US Veterans Health Administration (VHA) with actionable pharmacogenetic variants and evaluate how testing might be associated with prescribing decisions. This cross-sectional study included veterans who used national VHA pharmacy services from October 1, 2011, to September 30, 2017. Data analyses began April 26, 2018, and were completed February 6, 2019. Receipt of level A drugs based on VHA pharmacy dispensing records. Projected prevalence of actionable pharmacogenetic variants among VHA pharmacy users based on variant frequencies from the 1000 Genomes Project and veteran demographic characteristics; incident number of level A prescriptions, and proportion of new level A drug recipients projected to carry an actionable pharmacogenetic variant. During the study, 7 769 359 veterans (mean [SD] age, 58.1 [17.8] years; 7 021 504 [90.4%] men) used VHA pharmacy services. It was projected that 99% of VHA pharmacy users would carry at least 1 actionable pharmacogenetic variant. Among VHA pharmacy users, 4 259 153 (54.8%) received at least 1 level A drug with 1 188 124 (15.3%) receiving 2 drugs, and 912 189 (11.7%) receiving 3 or more drugs. The most common incident prescriptions during the study were tramadol (923 671 new recipients), simvastatin (533 928 new recipients), citalopram (266 952 new recipients), and warfarin (205 177 new recipients). Gene-drug interactions projected to have substantial clinical impacts in the VHA population include the interaction of SLCO1B1 with simvastatin (1 988 956 veterans [25.6%]), CYP2D6 with tramadol (318 544 veterans [4.1%]), and CYP2C9 or VKORC1 with warfarin (7 163 349 veterans [92.2%]). Clinically important pharmacogenetic variants are highly prevalent in the VHA population. Almost all veterans would carry an actionable variant, and more than half of the population had been exposed to a drug affected by these variants. These results suggest that pharmacogenetic testing has the potential to affect pharmacotherapy decisions for commonly prescribed outpatient medications for many veterans.

Identifiants

pubmed: 31173123
pii: 2735464
doi: 10.1001/jamanetworkopen.2019.5345
pmc: PMC6563578
doi:

Substances chimiques

Liver-Specific Organic Anion Transporter 1 0
Prescription Drugs 0
SLCO1B1 protein, human 0
Tramadol 39J1LGJ30J
Warfarin 5Q7ZVV76EI
Simvastatin AGG2FN16EV
CYP2C9 protein, human EC 1.14.13.-
Cytochrome P-450 CYP2C9 EC 1.14.13.-
Cytochrome P-450 CYP2D6 EC 1.14.14.1
VKORC1 protein, human EC 1.17.4.4
Vitamin K Epoxide Reductases EC 1.17.4.4

Types de publication

Journal Article Multicenter Study Observational Study Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e195345

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK101478
Pays : United States

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Auteurs

Catherine Chanfreau-Coffinier (C)

US Department of Veterans Affairs, VA Informatics and Computing Infrastructure, Salt Lake City Health Care System, Salt Lake City, Utah.

Leland E Hull (LE)

Center for Healthcare Organization and Implementation Research, US Department of Veterans Affairs, Boston Healthcare System, Boston, Massachusetts.
US Department of Veterans Affairs, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts.

Julie A Lynch (JA)

US Department of Veterans Affairs, VA Informatics and Computing Infrastructure, Salt Lake City Health Care System, Salt Lake City, Utah.
US Department of Veterans Affairs, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts.
College of Nursing and Health Sciences, University of Massachusetts, Boston.

Scott L DuVall (SL)

US Department of Veterans Affairs, VA Informatics and Computing Infrastructure, Salt Lake City Health Care System, Salt Lake City, Utah.
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City.

Scott M Damrauer (SM)

Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Corporal Michael Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania.

Francesca E Cunningham (FE)

US Department of Veterans Affairs Center for Medication Safety, Pharmacy Benefits Management Services, Hines, Illinois.

Benjamin F Voight (BF)

Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Michael E Matheny (ME)

Geriatrics Research Education and Clinical Care Center, US Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville.
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee.

David W Oslin (DW)

Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Corporal Michael Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania.

Michael S Icardi (MS)

US Department of Veterans Affairs Iowa City Healthcare System, Iowa City, Iowa.
US Department of Veterans Affairs National Office of Pathology and Laboratory Medicine, Iowa City, Iowa.
Carver College of Medicine, University of Iowa, Iowa City.

Sony Tuteja (S)

Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Corporal Michael Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania.

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Classifications MeSH