Medical Policy

Policy Num:       11.003.086
Policy Name:     KIF6 Genotyping for Predicting Cardiovascular Risk
Policy ID:          [11.003.086][Ar B M- P-][2.04.67]

Last Review:       August 20, 2021
Next Review:      Policy Archived
Issue:                   August, 2021

Archived

Related Policies: None

KIF6 Genotyping for Predicting Cardiovascular Risk

Summary

Genetic testing to determine kinesin-like protein 6 (KIF6) Trp719Arg variant status is being evaluated as a test to predict the risk of future cardiovascular events and as a test to predict response to statin therapy, particularly in high-risk patients.

For individuals who are asymptomatic with risk of cardiovascular disease and undergoing treatment with statin therapy who receive testing for KIF6 Trp719Arg variant status, the evidence includes secondary analyses of randomized controlled trials, case-control studies, and a quasi-experimental single-arm study. Relevant outcomes are overall survival, test accuracy and validity, change in disease status, morbid events, and medication use. Data supporting the association between KIF6 variant status and coronary artery disease outcomes are contradictory. The most recent evidence from large populations with different vascular disease risk levels has not supported a significant association between coronary artery disease risk and the presence of the variant. Further, studies of the association between response to statin therapy and KIF6 variant status are mixed. However, a large meta-analysis has shown that carriers of the KIF6 variant derive greater clinical benefit from low-density lipoprotein cholesterol reduction (a 13% reduction in the risk of coronary artery disease outcomes) compared with noncarriers. Currently, no prospective randomized controlled trials have evaluated the impact of testing for KIF6 variants on changes in clinical management (eg, intensifying the statin treatment in carriers, use of alternative approaches for lipid management in noncarriers) or outcomes. One nonrandomized study has suggested that subjects with KIF6 genotype results showed greater adherence to statin therapy, but, overall, it is uncertain whether testing for KIF 6 variants will alter the clinical management decisions. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Objective

The objective of this evidence review is to determine whether genetic testing for kinesin-like protein 6 (KIF6) Trp719Arg variant status predicts the response to statin therapy for patients at risk for cardiovascular disease and improves the net health outcome.

Policy Statements

KIF6 genotyping is considered investigational for predicting cardiovascular risk and/or the effectiveness of statin therapy.

Policy Guidelines

Coding

Please see the Codes table for details.

Benefit Application

BlueCard/National Account Issues

Some Plans may have contract or benefit exclusions for genetic testing.

Background

Kinesin-like protein 6 (KIF6) belongs to the kinesin superfamily of proteins involved in intracellular transport. The exact function of the KIF6 gene product is as yet undetermined. It has been reported that the gene is not expressed in the vasculature, the primary site of atherosclerosis, but is expressed in low levels in the brain, connective tissue, colon, eye, pharynx, skin, and testes.^1, In contrast, a study presented at a 2010 American Heart Association scientific session reported on data derived from tissue immunohistochemistry, locating KIF6 protein in macrophages surrounding neovessels and in foam cells in human atherosclerotic lesions.^2, Nevertheless, there is no strong evidence that KIF6 protein plays a direct biologic role in atherosclerosis, lipid metabolism, coronary artery disease (CAD), or myocardial infarction.

Analyses of prospective observational studies of cardiovascular health and the placebo arm of randomized controlled trials of statin interventions in at risk populations have suggested a significant association between the arginine-to-tryptophan substitution at position 719 (Trp719Arg) single nucleotide variant (rs20455) in KIF6 and the development of clinical CAD. Approximately 60% of the population carries the putative KIF6 high-risk 719Arg allele.^3, Moreover, carriers of the 719Arg allele in the treatment arms of the statin trials appeared to be at no increased or decreased risk of CAD or recurrent myocardial infarction, depending on the intensity of the statin therapy. These results have supported the development of a KIF6 Trp719Arg genotyping test for use as a predictor of CAD risk and the likely effectiveness of statin therapy.

Regulatory Status

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug Administration (FDA) has chosen not to require any regulatory review of this test.

In January 2011, Celera Corp. submitted a premarket approval application to FDA for its KIF6 Genotyping Assay performed using Abbott's m2000™ instrument system. In April, FDA informed Celera that its application was not approvable "without major amendment." The data and publications submitted were deemed "…insufficient to demonstrate the safety and effectiveness of the device for its proposed intended use." FDA indicated that additional data on clinical utility might be required, which could include conducting a randomized controlled trial.

Now a wholly owned subsidiary of Quest Diagnostics, Celera holds a U.S. patent on methods of determining coronary heart disease risk through detection of the KIF6 gene variant and reduction of such increased risk by atorvastatin and pravastatin therapy and offers the Cardio IQ™ KIF6 Genotype.

Rationale

This evidence review was created in January 2011 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through March 22, 2021.

Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.

Population Reference No. 1 Policy Statement

KIF6 Genotyping

Clinical Context and Test Purpose

The purpose of testing for kinesin-like protein 6 (KIF6) gene variants in patients receiving statin therapy for coronary artery disease (CAD) is to inform a decision about whether an individual who has a variant is at a higher risk of a future cardiovascular event, and therefore statin treatment should be initiated or the existing statin dose should be increased.

The questions addressed in this evidence review are: (1) Is there evidence that testing for variants in the KIF6 gene has clinical validity?; and (2) Does patient management change in a way that would improve outcomes as a result of testing?

The following PICO was used to select literature to inform this review.

Populations

The population of interest includes patients who are initiating or are being treated with statins for primary or secondary prevention of cardiovascular disease.

Interventions

The test being considered is genetic testing for variants in the KIF6 gene to guide initiation or intensification of statin therapy. The test detects a gene variant associated with increased coronary heart disease risk, and classifies patients as homozygous (normal risk) or heterozygous or homozygous carriers of Trp719Arg polymorphism for KIF6 (increased risk). Presence of a KIF6 variant is purported to predict response to statin therapy. The available version of the test is the Cardio IQ™ KIF6 Genotype.

Comparators

The following practice is currently being used: standard clinical care without genetic testing, in which decisions about medical therapy are based on standard lipid levels and risk factors for CAD (eg, smoking, weight, diet, diabetes, family history of CAD). The intensity of therapies is based on a continued monitoring of response to treatment (eg, achieving target low-density lipoprotein [LDL] reduction).

The intended use of the test to supplement versus replace standard clinical care without genetic testing is not fully delineated.

Outcomes

The primary outcomes of interest for this review are CAD events and mortality over a 10-year period. The maximum duration of follow-up for outcomes of interest in this review ranged from approximately 3 to 5 years in most studies. The potential beneficial outcomes from a true positive test result are potential reductions in CAD events and mortality following statin initiation or dose intensification. The potential beneficial outcomes from a true negative test result are avoidance of adverse drug events from statin initiation or dose intensification. The potential harmful outcomes are those resulting from a false test result. False-positive test results can lead to the initiation of unnecessary treatment and adverse events from that treatment. False-negative test results could also lead to undertreatment and CAD events that otherwise could have been avoided with appropriate treatment.

Technically Reliable

Assessment of technical reliability focuses on specific tests and operators and requires review of unpublished and often proprietary information. Review of specific tests, operators, and unpublished data are outside the scope of this evidence review and alternative sources exist. This evidence review focuses on the clinical validity and clinical utility.

Clinically Valid

A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence

Multiple studies have reported on the association between the KIF6 Trp719Arg single nucleotide variant (SNV) and the risks of CAD and response to statin therapy, with varying results about the strength and direction of the association. These studies include early retrospective evaluations of prospective, observational studies (see Table 1, part 1); retrospective evaluations of the placebo arms of randomized controlled trials (RCTs) of statin therapy (see Table 1, part 2); large meta-analysis of 19 case-control studies (see Table 1, part 3); and a retrospective evaluation of more recently conducted RCTs (see Table 1, part 4).

Patient populations in these studies included relatively unselected prevention cohorts and those with a higher risk of a CAD event. In prospective, observational studies and the placebo arms of RCTs, theTrp719Arg variant was positively associated with some CAD-related outcomes. In some RCTs, 719Arg variant carriers had larger decreases in coronary heart disease (CHD) risk in association with statin treatment than noncarriers.^3,4,5,6,

However, a large meta-analysis of 19 case-control studies found no association between the Trp719Arg SNV and nonfatal CAD.^7, A major limitation of this meta-analysis was the exclusion of fatal coronary disease events and inability to examine whether the effect on risk was modified by statin therapy. In addition to the findings of the meta-analysis, none of several, large genome-wide association studies evaluating CAD or myocardial infarction reported any SNVs at the KIF6 locus as significant.^{8,9,10,11,12,} Retrospective analyses of data from major RCTs published from 2011 to 2012 were consistent with the meta-analytic results, and statins were equally effective at reducing cardiovascular event rates among carriers and noncarriers of the KIF6 variant.^13,14,15,

In a retrospective analysis of 2 prospective trials, Arsenault et al (2012) investigated whether KIF6 variant carriers obtain more benefit from high-dose statin therapy.^16, The benefit was similar across all groups, except for those with homozygous variants, in whom there was a statistically significant benefit with a higher statin dose. However, the genotype by treatment interaction was not significant.

The conflicting results on the KIF6 variant, CHD, and treatment outcomes might have been explained in the meta-analysis by Ference et al (2011).^17, Reviewers selected 37 case-control studies, prospective cohort studies, or randomized trial treatment allocation arms (each considered as a separate cohort), which together enrolled 144,931 participants and reported 27,465 CHD events. The KIF6 genotype, particularly the Trp719Arg SNV carrier status, was not associated with increased risk of CHD event. However, for each millimole per liter increase in low-density lipoprotein cholesterol (LDL-C), KIF6 variant carriers experienced a 15% greater increase in the relative risk of CHD compared with noncarriers (ratio of relative risk, 1.15; 95% confidence interval [CI], 1.06 to 1.25, p=0.001). Similarly, the decrease in risk for each millimole per liter decrease in LDL was 13% higher for variant carriers. Also included in the meta-analysis were 8 randomized trials assessing statin therapy in 50,060 participants with 7307 CHD events. KIF6 variant carriers derived a greater clinical benefit for each millimole per liter reduction in LDL-C during treatment with a statin than did noncarriers (ratio of relative risk, 0.87; 95% CI, 0.77 to 0.99; p=0.038). Thus, the results suggested that the KIF6 Trp719Arg variant increases vulnerability to LDL-C. This result might explain why KIF6 variant carriers appear to derive greater clinical benefit from a statin even though the variant itself does not appear to affect the ability of the statin to lower LDL-C, nor does it appear to be independently associated with the risk of CHD on average. However, "the association between the KIF6 variant and the risk of CHD will vary according to the average LDL cholesterol level of the population(s) under study."^17,This association might also explain some of the conflicting reports of KIF6 genotype association with CHD.

Table 1. Results of Studies Investigating the Differential Effects of KIF6 Genotype on CV Outcomes and a Meta-Analysis of the Association Between KIF6 Genotype and CAD Outcomes

ARIC: Atherosclerosis Risk in Communities; CAD: coronary artery disease; CARE: Cholesterol and Recurrent Events trial; CHD: coronary heart disease; CHS: Cardiovascular Health Study; CI: confidence interval; CV: cardiovascular; CVD: cardiovascular disease; HPS: Heart Protection Study; HR: hazard ratio; IDEAL: Incremental Decrease in End Points Through Aggressive Lipid-Lowering; JUPITER: Justification for Use of Statins in Primary Prevention, An Intervention Trial Evaluating Rosuvastatin; LDL-C: low-density lipoprotein cholesterol; MI: myocardial infarction; NA: not applicable; OR: odds ratio; PROSPER: PROspective Study of Pravastatin in the Elderly at Risk; PROVE IT-TIMI 22: Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction 22 trial; RCT: randomized controlled trial; TNT: Treating to New Targets; T2D: type 2 diabetes; WHS: Women's Health Study; WOSCOPS: West of Scotland Coronary Prevention Study.
a Published.
b Calculated from published data.

Section Summary: Clinically Valid

There is uncertainty about the clinical validity of genetic testing for KIF6 Trp719Arg SNV due to conflicting results on the association between KIF6 variant carrier status and the risks of CAD and to conflicting results of the association between KIF6 variant carrier status and response to statin therapy.

Clinically Useful

A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

The potential clinical utility of genetic testing for KIF6 includes confirming a diagnosis and evaluating whether there is a modifiable treatment option that would lower the risk of CAD for that individual.

Review of Evidence

Direct Evidence

Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from randomized controlled trials.

Charland et al (2014) reported on the results of a prospective, nonrandomized, open-label, single-center trial designed to compare statin adherence at 6 months in those who learned about their KIF6 carrier status with those who did not.^22, Patients older than 18 years of age who were new to statin therapy (with no pharmacy electronic claims for statins in prior 6 months before the index date) were enrolled, and KIF6 genotyping was performed. KIF6 carrier status results were mailed to all individuals, including information on the association between KIF6 carriers and higher coronary heart disease risk reduction with statins. Patients not contacted for study participation were matched 1:1 with the final KIF6-tested group based on age, sex, index statin prescription fill channel (mail or retail pharmacy), and a number of unique chronic medications within 180 days of the statin index date to serve as controls. A secondary control cohort was created from patients who were contacted about the trial and made aware that their statin adherence might be routinely monitored but who declined study participation with KIF6 testing. The primary outcomes were statin prescription adherence and persistence, assessed using prescription claims records. Adherence was calculated as the proportion of days covered; subjects were adherent if they had 80% or more of the days covered. The proportion of patients categorized as adherent to statin therapy was 18.4% higher for the KIF6-tested group (63.4%; 95% CI, 59.6% to 67.1%) than for the matched controls (45.0%; 95% CI, 41.1% to 48.8%; p<0.001) and 12.7% higher than for the secondary control group (50.7%; 95% CI, 47.7% to 52.6%; p<0.001). While this trial reported an association between receipt of KIF6-genotype testing results and higher statin adherence, the nonrandomized trial design and the baseline differences between groups limit the validity of the results. The potential for bias in the self-selection of healthier patients for KIF6 genotyping and the inability to isolate the incremental effects of receiving the KIF6 genotype results over other aspects of study participation restrict the conclusions that can be drawn about the effect of KIF6 genotyping on adherence.

Chain of Evidence

Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility.

The conflicting evidence on clinical validity does not permit conclusions on clinical utility.

Section Summary: Clinically Useful

The clinical utility of genetic testing for the KIF6 variant has not been established. It is unclear whether genetic testing for the KIF 6 variant alters the clinical management decisions. One nonrandomized trial suggested that subjects who received KIF6 genotype results exhibited greater adherence to statin therapy, but the nonrandomized trial design and the baseline group differences limit the validity of the results. The potential for selection bias of healthier patients who volunteered for KIF6 genotyping and the inability to isolate the incremental effects of receiving the KIF6 genotype results over other aspects of trial participation restrict the conclusions that can be drawn about the effect of KIF6 genotyping on adherence. More importantly, no study has demonstrated whether KIF6 testing leads to changes in clinical management that reduce the risk of CAD

Summary of Evidence

For individuals who are asymptomatic with risk of cardiovascular disease and undergoing treatment with statin therapy who receive testing for KIF6 Trp719Arg variant status, the evidence includes secondary analyses of RCTs, case-control studies, and a quasi-experimental single-arm study. Relevant outcomes are overall survival, test accuracy and validity, change in disease status, morbid events, and medication use. Data supporting the association between KIF6 variant status and coronary artery disease outcomes are contradictory. The most recent evidence from large populations with different vascular disease risk levels has not supported a significant association between coronary artery disease risk and the presence of the variant. Further, studies of the association between response to statin therapy and KIF6 variant status are mixed. However, a large meta-analysis has shown that carriers of the KIF6 variant derive greater clinical benefit from low-density lipoprotein cholesterol reduction (a 13% reduction in the risk of coronary artery disease outcomes) compared with noncarriers. Currently, no prospective RCTs have evaluated the impact of testing for KIF6 variants on changes in clinical management (eg, intensifying the statin treatment in carriers, use of alternative approaches for lipid management in noncarriers) or outcomes. One nonrandomized study has suggested that subjects with KIF6 genotype results showed greater adherence to statin therapy, but, overall, it is uncertain whether testing for KIF 6 variants will alter the clinical management decisions. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Supplemental Information

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information’ if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

In 2019, the American College of Cardiology and American Heart Association issued a joint guideline on use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease, which made no reference to KIF6 genotyping.^23,

In 2013, the American College of Cardiology and the American Heart Association issued joint guidelines on the assessment of cardiovascular risk that did not address KIF6 genotyping.^24,

In 2010, the joint American College of Cardiology Foundation and American Heart Association practice guideline on the assessment of cardiovascular risk in asymptomatic adults made no reference to KIF6 genotyping.^25,26,

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force recommendations for KIF6 genotyping in coronary heart disease risk or use of KIF6 genotyping to guide the selection or use of statin therapy have been identified.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in May 2021 did not identify any ongoing or unpublished trials that would likely influence this review.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

References

1. Marian AJ. Surprises of the genome and "personalized" medicine. J Am Coll Cardiol. Jan 29 2008; 51(4): 456-8. PMID 18222356
2. 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 [Abstract P692]. Paper presented at: American Heart Association Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions; April 8-10, 2010; San Francisco, CA.
3. 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. Jan 29 2008; 51(4): 435-43. PMID 18222353
4. 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. Aug 2010; 17(4): 455-61. PMID 20215968
5. 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. May 01 2010; 105(9): 1300-5. PMID 20403483
6. 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. Jan 29 2008; 51(4): 449-55. PMID 18222355
7. 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. Nov 02 2010; 56(19): 1552-63. PMID 20933357
8. Samani NJ, Erdmann J, Hall AS, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. Aug 02 2007; 357(5): 443-53. PMID 17634449
9. 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. Mar 2009; 41(3): 334-41. PMID 19198609
10. McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. Jun 08 2007; 316(5830): 1488-91. PMID 17478681
11. Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. Jun 08 2007; 316(5830): 1491-3. PMID 17478679
12. Burton PR, Clayton DG, Cardon LR, et al. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. Jun 07 2007; 447(7145): 661-78. PMID 17554300
13. Ridker PM, MacFadyen JG, Glynn RJ, et al. Kinesin-like protein 6 (KIF6) polymorphism and the efficacy of rosuvastatin in primary prevention. Circ Cardiovasc Genet. Jun 2011; 4(3): 312-7. PMID 21493817
14. Hopewell JC, Parish S, Clarke R, et al. No impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study. J Am Coll Cardiol. May 17 2011; 57(20): 2000-7. PMID 21458191
15. Hoffmann MM, Marz W, Genser B, et al. Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and cardiovascular risk and efficacy of atorvastatin among subjects with diabetes on dialysis: the 4D study. Atherosclerosis. Dec 2011; 219(2): 659-62. PMID 21871624
16. Arsenault BJ, Boekholdt SM, Hovingh GK, et al. The 719Arg variant of KIF6 and cardiovascular outcomes in statin-treated, stable coronary patients of the treating to new targets and incremental decrease in end points through aggressive lipid-lowering prospective studies. Circ Cardiovasc Genet. Feb 01 2012; 5(1): 51-7. PMID 22135385
17. Ference BA, Yoo W, Flack JM, et al. A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis. PLoS One. 2011; 6(12): e28834. PMID 22216121
18. 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. Jul 01 2007; 166(1): 28-35. PMID 17443022
19. 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. Jan 2008; 28(1): 173-9. PMID 17975119
20. 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. Jan 29 2008; 51(4): 444-8. PMID 18222354
21. Akao H, Polisecki E, Kajinami K, et al. KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly. Atherosclerosis. Feb 2012; 220(2): 456-62. PMID 22192511
22. Charland SL, Agatep BC, Herrera V, et al. Providing patients with pharmacogenetic test results affects adherence to statin therapy: results of the Additional KIF6 Risk Offers Better Adherence to Statins (AKROBATS) trial. Pharmacogenomics J. Jun 2014; 14(3): 272-80. PMID 23979174
23. Lloyd-Jones DM, Braun LT, Ndumele CE, et al. Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology. J Am Coll Cardiol. Jun 25 2019; 73(24): 3153-3167. PMID 30423392
24. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. Jul 01 2014; 63(25 Pt B): 2935-2959. PMID 24239921
25. 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. Dec 21 2010; 122(25): e584-636. PMID 21098428
26. 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. Dec 14 2010; 56(25): e50-103. PMID 21144964

Codes

Appplicable Modifiers

N/A

Policy History

Payment Policy Guidelines

Administrative Evaluation

Investigational Policy. No pay.

Economic Impact

Interqual Criteria

Policy Categorization