Format

Send to

Choose Destination
JACC Cardiovasc Interv. 2018 Jan 22;11(2):181-191. doi: 10.1016/j.jcin.2017.07.022. Epub 2017 Nov 1.

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Author information

1
Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida. Electronic address: lcavallari@cop.ufl.edu.
2
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
3
Department of Medicine, University of Maryland, Baltimore, Maryland.
4
Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida; Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida.
5
Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, Illinois.
6
Department of Medicine, Center for Applied Genomics & Precision Medicine, Duke University, Durham, North Carolina.
7
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
8
Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida.
9
Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida.
10
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
11
Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida.
12
Division of Cardiovascular Sciences, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
13
Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, Illinois.
14
Veterans Administration Medical Center, Baltimore, Maryland.
15
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida.
16
Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania.
17
Departments of Biomedical Informatics and Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
18
Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
19
Department of Pathology and Hugh Kaul Personalized Medicine Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
20
Heart South Cardiovascular Group, Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.
21
Department of Neuropsychology, University of North Dakota, Fargo, North Dakota.
22
Division of Cardiology and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
23
College of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida.
24
Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, Illinois; Department of Pharmacy Systems, Outcomes and Policy and Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago College of Pharmacy, Chicago, Illinois.
25
Department of Medicine, University of Maryland, Baltimore, Maryland; Veterans Administration Medical Center, Baltimore, Maryland.
26
Department of Medicine, Krannert Institute of Cardiology & Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana.
27
Department of Medicine, University of South Dakota, Sanford School of Medicine, Sioux Falls, South Dakota.
28
Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
29
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
30
Department of Neurology and Hugh Kaul Personalized Medicine Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
31
Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida; Department of Epidemiology, Colleges of Medicine and Public Health and Health Professions, University of Florida, Gainesville, Florida.

Abstract

OBJECTIVES:

This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).

BACKGROUND:

CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.

METHODS:

After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.

RESULTS:

Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).

CONCLUSIONS:

These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

KEYWORDS:

CYP2C19; antiplatelet therapy; cardiovascular events; clopidogrel; percutaneous coronary intervention; pharmacogenomics

PMID:
29102571
PMCID:
PMC5775044
[Available on 2019-01-22]
DOI:
10.1016/j.jcin.2017.07.022

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center