State-of-the-Art Paper
Clinical Application of Cardiovascular Pharmacogenetics

https://doi.org/10.1016/j.jacc.2012.01.067Get rights and content
Under an Elsevier user license
open archive

Pharmacogenetics primarily uses genetic variation to identify subgroups of patients who may respond differently to a certain medication. Since its first description, the field of pharmacogenetics has expanded to study a broad range of cardiovascular drugs and has become a mainstream research discipline. Three principle classes of pharmacogenetic markers have emerged: 1) pharmacokinetic; 2) pharmacodynamic; and 3) underlying disease mechanism. In the realm of cardiovascular pharmacogenetics, significant advances have identified markers in each class for a variety of therapeutics, some with a potential for improving patient outcomes. While ongoing clinical trials will determine if routine use of pharmacogenetic testing may be beneficial, the data today support pharmacogenetic testing for certain variants on an individualized, case-by-case basis. Our primary goal is to review the association data for the major pharmacogenetic variants associated with commonly used cardiovascular medications: antiplatelet agents, warfarin, statins, beta-blockers, diuretics, and antiarrhythmic drugs. In addition, we highlight which variants and in which contexts pharmacogenetic testing can be implemented by practicing clinicians. The pace of genetic discovery has outstripped the generation of the evidence justifying its clinical adoption. Until the evidentiary gaps are filled, however, clinicians may choose to target therapeutics to individual patients whose genetic background indicates that they stand to benefit the most from pharmacogenetic testing.

Key Words

clopidogrel
pharmacogenetics
polymorphism
statins
warfarin

Abbreviations and Acronyms

ACS
acute coronary syndrome(s)
BP
blood pressure
CYP
cytochrome P450
GWAS
genome-wide association study
HR
heart rate
INR
international normalized ratio
LDLc
low-density lipoprotein cholesterol
LVEF
left ventricular ejection fraction
MI
myocardial infarction
PCI
percutaneous coronary intervention
RF
reduced function
SNP
single nucleotide polymorphism

Cited by (0)

Dr. Voora has reported he has no relationships relevant to the contents of this paper to disclose. Dr. Ginsburg is a scientific advisor to CardioDx.