Notification



Notification Issue Date:



Policy Attachment

Attachment to Policy # MA06.008b


Attachment:F

Policy #:MA06.008b

Description:Pharmacogenetic Testing for Predicting Cardiovascular Risk and/or Effectiveness of Statin Therapy by KIF6 Genotyping

Title:Pharmacogenetic Testing to Determine Drug Sensitivity

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.


Title: Pharmacogenetic Testing for Predicting Cardiovascular Risk and/or Effectiveness of Statin Therapy by KIF6 Genotyping


POLICY

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

Pharmacogenetic testing for predicting cardiovascular risk and/or effectiveness of statin therapy by KIF6 genotyping is considered experimental/investigational and, therefore, not covered.

POLICY GUIDELINES

This policy is consistent with Medicare's coverage determination. The Company's payment methodology may differ from Medicare.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, pharmacogenetic testing for predicting cardiovascular risk and/or effectiveness of statin therapy by KIF6 genotyping is not eligible for payment under the medical benefits of the Company's Medicare Advantage products because the service is considered experimental/investigational.

Services that are experimental/investigational are excluded from the Company's Medicare Advantage products. Therefore, they are not eligible for reimbursement consideration.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Genetic testing is a laboratory procedure and is historically not regulated by the US Food and Drug Administration (FDA). Clinical Laboratory Improvement Amendments (CLIA) establishes quality standards for all laboratory testing. However, recently, the FDA is reported to be involved in the evaluation of the service of genetic testing.

DESCRIPTION

Genetic testing to determine the KIF6 Trp719 variant status of individuals is being investigated for use as a predictor for future cardiac events, as well as a predictor of response to statin therapy, particularly in those individuals considered high risk.

Coronary artery disease (CAD) is a leading cause of mortality worldwide, with estimates that CAD is responsible for more than 500,000 deaths annually. Risk factors for development of CAD include smoking, obesity, high low-density lipoprotein (LDL) cholesterol levels, low high-density lipoprotein (HDL) cholesterol levels, hypertension, lack of physical activity, and a family history of CAD.

Genome studies have revealed that there are connections between a number of common single nucleotide polymorphisms (SNPs) and CAD and other cardiovascular diseases. The KIF6 TrpArg test genotypes this SNP in the KIF6 gene via polymerase chain reaction (PCR) and allele-specific oligonucleotide ligation. Some published literature, including observational studies, as well as the placebo arms of randomized control trials (RCTs) of statin use in populations considered at risk, show an association between the Trp719Arg SNP in the KIF6 protein and the development of (CAD).

The potential biological role of the KIF6 protein in a number of CAD-related outcomes has not been established. Therefore, clinical validity of this variant needs further investigation due to the lack of strong evidence that verifies its role in, for example, lipid metabolism and myocardial infarction (MI). Furthermore, current data has not shown that KIF6 genotyping can directly improve patient management.

Celera Corporation (Berkeley, CA) holds the patent relating to determining heart attack risk by identifying the KIF6 variant gene, and its subsidiary, Berkeley HeartLab (Alameda, CA), has been offering KIF6 genotyping via the KIF6-StatinCheck Genotype Test.

The KIF6 test is not manufactured, and thus has not been reviewed by the FDA. It is a laboratory developed test, which is offered by clinical laboratories licensed under the Clinical Laboratory Improvement Amendments (CLIA). Celera Corporation holds a US patent for this test, the KIF6 Statin Check Genotype Test, and several subsidiary labs offer KIF6 genotyping through Berkeley HeartLab (CA).

No reference to KIF6 genotyping was found at the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) Practice Guidelines for Assessment of Cardiovascular Risk in Asymptomatic Adults.

REFERENCES

Allingham-Hawkins D, Lea A, Levine S. KIF6 p.Trp719Arg testing to assess risk of coronary artery disease and/or statin response. PLoS Curr. 2010;2:RRN1191.

Assimes TL, Holm H, Kathiresan S, et al. Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and coronary artery disease in 19 case-control studies. J Am Coll Cardiol. 2010;56(19):1552-63.

Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010;122(25):e584-636.

Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010;122(25):e584-636.

Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010;56(25):e50-103.

Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316(5830):1491-3.

Iakoubova OA, Robertson M, Tong CH, et al. KIF6 Trp719Arg polymorphism and the effect of statin therapy in elderly patients: results from the PROSPER study. Eur J Cardiovasc Prev Rehabil. 2010;17(4):455-61.

Iakoubova OA, Tong CH, Rowland CM, et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J Am Coll Cardiol. 2008;51(4):435-43.

Iakoubova OA, Sabatine MS, Rowland CM, et al. Polymorphism in KIF6 gene and benefit from statins after acute coronary syndromes: results from the PROVE IT-TIMI 22 study. J Am Coll Cardiol. 2008;51(4):449-55.

Kathiresan S, Voight BF, Purcell S, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41(3):334-41.

Li Y, Iakoubova OA, Shiffman D, et al. KIF6 polymorphism as a predictor of risk of coronary events and of clinical event reduction by statin therapy. Am J Cardiol. 2010;106(7):994-8.

Marian AJ. Surprises of the genome and "personalized" medicine. J Am Coll Cardiol. 2008;51(4):456-8.

Rosenfeld ME, Preusch M, Shiffman D, et al. KIF6, an Emerging Coronary Heart Disease Risk Marker Expressed by Macrophages in Atherosclerotic Lesions in Humans and Mice. American Heart Association Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions. 2010;P692.

McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316(5830):1488-91.

Morrison AC, Bare LA, Chambless LE, et al. Prediction of coronary heart disease risk using a genetic risk score: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 2007;166(1):28-35.

Samani NJ, Erdmann J, Hall AS, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443-53.

Shiffman D, Chasman DI, Zee RY, et al. A kinesin family member 6 variant is associated with coronary heart disease in the Women's Health Study. J Am Coll Cardiol. 2008;51(4):444-8.

Shiffman D, O'Meara ES, Bare LA, et al. Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol. 2008;28(1):173-9.

Shiffman D, Sabatine MS, Louie JZ, et al. Effect of pravastatin therapy on coronary events in carriers of the KIF6 719Arg allele from the cholesterol and recurrent events trial. Am J Cardiol. 2010;105(9):1300-5.

Stewart, AF, Dandona S. Chen L, et al. Kinesin family member 6 variant Trp719Arg does not associate with angiographically defined coronary diseae in the Ottawa Heart Genomics Study. J Am Coll Cardiol. 2009;53 (16):1471-1472.

Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661-78.


Coding Table

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.


Code System
Code Number and Narrative
CPT81479
ICD DiagnosisN/A
HCPCS Level IIN/A
ModifiersN/A
Revenue CodesN/A


Version Effective Date: 07/01/2016
Version Issued Date: 07/01/2016
Version Reissued Date: 10/10/2019

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