Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a challenge for clinical implementation.

@article{Ong2012ClinicalUO,
  title={Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a challenge for clinical implementation.},
  author={Frank Shih-Chang Ong and Joshua L. Deignan and Jane Zea-Chin Kuo and Kenneth E. Bernstein and Jerome I. Rotter and Wayne W. Grody and Kingshuk Das},
  journal={Pharmacogenomics},
  year={2012},
  volume={13 4},
  pages={
          465-75
        }
}
In the past decade, significant strides have been made in the area of cardiovascular pharmacogenomic research, with the discovery of associations between certain genotypes and drug-response phenotypes. While the motivations for personalized and predictive medicine are promising for patient care and support a model of health system efficiency, the implementation of pharmacogenomics for cardiovascular therapeutics on a population scale faces substantial challenges. The greatest obstacle to… 

Tables from this paper

Benefits of Pharmacogenetics in the Management of Hypertension
TLDR
The introduction of changes in the management of hypertension in the Spanish population could be useful to promote the prevention and treatment of high blood pressure in a more efficient way and the integration of pharmacogenetic testing into routine clinical procedures could optimize the therapeutic response.
Pharmacogenomics of adverse drug reactions: implementing personalized medicine.
TLDR
This review focuses on the pharmacogenomics of ADRs, the underlying mechanisms and the potential use of genomic biomarkers in clinical practice for dose adjustment and the avoidance of drug toxicity.
The emerging era of pharmacogenomics: current successes, future potential, and challenges
TLDR
Some of the challenges, and potential solutions, that remain for the implementation of pharmacogenomic testing into clinical practice for the significant improvement of drug safety are discussed.
Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels.
TLDR
It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist, and how frequently testing is recommended should be reviewed.
Review of the Reported Measures of Clinical Validity and Clinical Utility as Arguments for the Implementation of Pharmacogenetic Testing: A Case Study of Statin-Induced Muscle Toxicity
TLDR
A systematic review of current reporting in scientific literature was conducted on publications addressing PGx in the context of statins and muscle toxicity to address a lack of reporting on clinical validity and clinical utility of PGx-tests.
Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing
TLDR
The current commonly used predictive pharmacogenetic biomarkers in clinical oncology molecular testing are discussed, including BRAF V600E for vemurafenib in melanoma and ERBB2 (HER2/neu) for trastuzumab in breast cancer.
Personalized Medicine in Ophthalmology: From Pharmacogenetic Biomarkers to Therapeutic and Dosage Optimization
TLDR
Application of recent developments in nanoemulsion and polymeric micelle for targeted delivery and drug release are models of dosage optimization, increasing efficacy and improving outcomes in these major eye diseases.
Variable Drug Response: Genetic Evaluation
TLDR
The field of pharmacogenomics attempts to evaluate the contribution of genetic variants to drug sensitivity and adverse effects by using candidate gene approaches to application of genome-wide approaches for the identification of genetic variant associated with drug responses.
Whole-genome sequencing in pharmacogenetics.
  • T. Urban
  • Medicine, Biology
    Pharmacogenomics
  • 2013
TLDR
GWAS of drug response traits are quite exceptional in having provided a number of clinically significant genetic predictors of drug outcomes, with estimated effect sizes sometimes orders of magnitude greater than those seen for any human disease.
Evidence to Support Inclusion of Pharmacogenetic Biomarkers in Randomised Controlled Trials
TLDR
A review of five pharmacogenetic biomarker-guided randomised controlled trials and evaluated the evidence used by these trials to justify biomarker inclusion to write recommendations for future justifications of biomarker use in RCTs and encourage regulatory authorities to write clear guidelines.
...
...

References

SHOWING 1-10 OF 100 REFERENCES
Cardiovascular Pharmacogenomics of Adrenergic Receptor Signaling: Clinical Implications and Future Directions
TLDR
Results for selected ARs and associated regulatory kinases relative to the pharmacogenomics of β‐blocker treatment for hypertension and heart failure are reviewed, highlighting the linking of clinical results to molecular mechanisms, and discussing study design limitations are discussed.
Genetic determinants of response to clopidogrel and cardiovascular events.
TLDR
Among patients with an acute myocardial infarction who were receiving clopidogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than those who were not, particularly marked among the patients undergoing percutaneous coronary intervention.
Pharmacogenomics of antihypertensive drugs: past, present and future.
TLDR
It seems clear that collaboration among researchers to allow replication or joint analyses will be essential in advancing the field, as will the use of genome-wide association approaches.
Effects of CYP2C19 genotype on outcomes of clopidogrel treatment.
TLDR
Among patients with acute coronary syndromes or atrial fibrillation, the effect of clopidogrel as compared with placebo is consistent, irrespective of CYP2C19 loss-of-function carrier status.
Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy.
TLDR
CYP2C19*2 genotype was associated with diminished platelet response to clopidogrel treatment and poorer cardiovascular outcomes, and patients with the CYP2C 19*2 variant were more likely to have a cardiovascular ischemic event or death during 1 year of follow-up.
Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin
TLDR
The goal was to develop and validate a pharmacogenetic algorithm that explained 53–54% of the variability in the warfarin dose in the derivation and validation cohorts.
Pharmacogenetic Study of Statin Therapy and Cholesterol Reduction
TLDR
Individuals heterozygous for a genetic variant in the HMG-CoA reductase gene may experience significantly smaller reductions in cholesterol when treated with pravastatin.
Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing
TLDR
The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 genotype data for estimating therapeutic warfarin dose to achieve an INR of 2–3, should genotype results be available to the clinician.
SLCO1B1 variants and statin-induced myopathy--a genomewide study.
TLDR
Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively and identify common variants in SLCO1B1 that are strongly associated with an increased risk ofstatin-induced myopathy.
...
...