Clinical Policy Title: Statin use in adults and children

Transcription

1 Clinical Policy Title: Statin use in adults and children Clinical Policy Number: Effective Date: May 1, 2016 Initial Review Date: February 17, 2016 Most Recent Review Date: September 21, 2017 Next Review Date: September 2018 Related policies: Policy contains: Cardiovascular disease (CVD) Hypercholesterolemia Statins cholesterol lowering drugs (e.g. simvastatin, pravastatin, atorvastatin) Familial hypercholesterolemia None. ABOUT THIS POLICY: Select Health of South Carolina has developed clinical policies to assist with making coverage determinations. Select Health of South Carolina s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peerreviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Select Health of South Carolina when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Select Health of South Carolina s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Select Health of South Carolina s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Select Health of South Carolina will update its clinical policies as necessary. Select Health of South Carolina s clinical policies are not guarantees of payment. Coverage policy Select Health of South Carolina considers the use of statins in adults and children to be clinically proven and, therefore, medically necessary when the following criteria are met (Vuorio 2017 & 2014, Pencina 2014, Huffman2013, Espinheira 2013, American College of Cardiology and the American Heart Association [ACC-AHA] 2013, Avis 2007): Presence of (as defined in the ACC-AHA guidelines): Hypercholesterolemia Familial hypercholesterolemia Cardiovascular disease Diabetes mellitus Limitations: All other uses of statins in adults and children are not medically necessary. Alternative covered services: 1

2 None. Background Cardiovascular disease (CVD), which comprises heart attacks (myocardial infarction), angina and strokes, is ranked as the number one cause of mortality and is a major cause of morbidity world wide. High blood cholesterol is linked to CVD events and is an important risk factor. Reducing high blood cholesterol, is thus an important way to reduce the chances of suffering a CVD event. Statins cholesterol lowering drugs (e.g. simvastatin, pravastatin, atorvastatin) are the first-line treatment for high cholesterol. Since the early statin randomized controlled trials were reported in the 1990s, several reviews of the effects of statins have been published highlighting their benefits particularly in people with a past history of CVD. Benefits include a reduction in CVD events. Statins have also been shown to reduce the risk of a first event in otherwise healthy individuals at high risk of CVD (primary prevention) but information on possible hazards has not been reported fully. Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on highly elevated low-density lipoprotein (LDL) cholesterol level or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong hypolipidemic measures, started in childhood, are recommended to reduce the risk of cardiovascular disease. In children, hypercholesterolemia results from an alteration, genetic or acquired, in lipoprotein metabolism. It is possible to maintain a normal lipid profile in most individuals with familial hypercholesterolemia in order to reduce the risk of early onset of atherosclerosis, which is associated with serious cardiovascular complications from childhood. In children with familial hypercholesterolemia, diet is the cornerstone of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective, but are poorly tolerated. Since the 1990s statin studies have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years). Statins greatly reduced their serum LDL cholesterol levels. Even though statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. Searches Select Health of South Carolina searched PubMed and the databases of: UK National Health Services Center for Reviews and Dissemination. 2

3 Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on September 6, Searched terms were: "familial hypercholesterolemia (MeSH)","pediatric hypercholesterolemia (MeSH)" and "statin use in adults and children." We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings A systematic review (Pencina 2014) to assess the effects, both in terms of benefits and harms of statins, for the primary prevention of CVD found 18 randomized controlled trials with 19 trial arms (56,934 patients) dating from 1994 to All were randomized control trials comparing statins with usual care or placebo. The mean age of the participants was 57 years (range years), 60.3% were men, and of the eight trials that reported on ethnicity, 85.9 % were Caucasian. Duration of treatment was a minimum one year and with follow-up of a minimum of six months. All-cause mortality and fatal and non-fatal CVD events were reduced with the use of statins as was the need for revascularization (the restoration of an adequate blood supply to the heart) by means of surgery (coronary artery bypass graft ) or by angioplasty (PTCA). Of 1000 people treated with a statin for five years, 18 would avoid a major CVD event which compares well with other treatments used for preventing cardiovascular disease. Taking statins did not increase the risk of serious adverse effects such as cancer. Statins are likely to be cost-effective in primary prevention. A systematic review (Huffman2013) examined eighteen randomized control trials (19 trial arms; 56,934 participants) that recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria) to study the effect of statins on primary prevention of CVD. All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularization rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. The evidence suggests that primary prevention with statins is likely to be cost- 3

4 effective and may improve patient quality of life. Reductions in all-cause mortality, major vascular events and revascularizations were found with no excess of adverse events among people without evidence of CVD treated with statins. The 2013 guidelines of the American College of Cardiology and the American Heart Association (ACC- AHA) for the treatment of cholesterol expand the indications for statin therapy for the prevention of cardiovascular disease. Using data from the National Health and Nutrition Examination Surveys of 2005 to 2010, ACC-AHA estimated the number, and summarized the risk-factor profile, of persons for whom statin therapy would be recommended. Under the new ACC-AHA guidelines there is an estimated population of million U.S. adults between the ages of 40 and 75 years who may benefit from this treatment. In many cases, indication would exist among adults without clinically overt cardiovascular disease. Among adults between the ages of 60 and 75 years without cardiovascular disease who are not receiving statin therapy, the percentage for whom such therapy would be indicated may increase from 30.4% to 87.4% among men and from 21.2% to 53.6% among women. This effect would be driven largely by an increased number of adults who would be classified solely on the basis of their 10-year risk of a cardiovascular event. Those who would be newly eligible for statin therapy include more men than women and persons with a higher blood pressure but a markedly lower level of low-density lipoprotein cholesterol. The new guidelines recommend statin therapy for more adults who would be expected to have future cardiovascular events (higher sensitivity) but would also include many adults who would not have future events (lower specificity). Only a few studies of statin use have included older individuals, particularly ages 80 years or older. A recent narrative review (Desai 2012) of statin in this population found the association of adverse effects with intensive doses of statin and their interactions with other drugs may be more problematic in older adults. Statin therapy appears cost-effective for individuals with higher CVD risk but this is dependent on the assumptions used. The authors concluded that evidence remains limited regarding the overall benefit of starting statin therapy in adults ages 80 years and older; thus, clinical judgment remains necessary in making this decision. A randomized controlled trial (Espinheira 2013) of a total of 168 children found that forty-six presented a familial hypercholesterolemia phenotype, and in 22 of these, a mutation in the low-density lipoprotein (LDL) receptor gene was identified. The lipid profile of the group with mutations showed significantly higher values of total and non-high-density lipoprotein (HDL) cholesterol compared to the group without mutations (total cholesterol 316.5±75.9 mg/dl vs ±42,0 mg/dl; non-hdl cholesterol 268.3±72.6 mg/dl vs ±43.9 mg/dl; p<0.05). Of the total, 55 were prescribed pharmacological therapy and the others underwent diet and exercise interventions only. A greater reduction in LDL cholesterol was observed in individuals under pharmacological therapy compared to those prescribed diet and exercise only (30.3% vs. 18.1%). The evidence suggests that hypercholesterolemia is associated with the atherosclerotic process from childhood, and that pediatric hypercholesterolemia justifies the screening of high-risk children and initiation of therapy at preschool ages. 4

5 A systematic review of 21 studies, of which eight were randomized placebo-controlled studies (1074 participants), Vuorio (2014) found that statins reduced the mean LDL cholesterol concentration at all time points from six weeks to two years. The risks of myopathy and clinical adverse events were very low in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery, and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness. The authors concluded that statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified; however, long-term safety is unknown. A systematic review and meta-analysis (Avis 2007) of statin therapy in children with familial hypercholesterolemia aged 8 to 18 years examined six pertinent studies (n=798 children) inclusive of 12 to 104 weeks of treatment. Total cholesterol, LDL cholesterol, and apolipoprotein B were significantly reduced, whereas HDL cholesterol and apolipoprotein A1 were significantly increased by statin therapy. No statistically significant differences were found between statin- and placebo-treated children with respect to the occurrence of adverse events (RR 0.99; 95% CI: 0.79 to 1.25), sexual development (RR of advancing > or = 1 stage in Tanner classification 0.96; 95% CI: 0.79 to 1.17), muscle toxicity (RR of CK > or = 10 times the upper limit of normal [ULN] 1.38; 95% CI: 0.18 to 10.82), or liver toxicity (RR of > or = 3 times the ULN for ASAT 0.98; 95% CI: 0.23 to 4.26 and for ALAT 2.03; 95% CI: 0.24 to 16.95). The authors found a minimal difference in growth in favor of the statin group (0.33 cm; 95% CI: 0.03 cm to 0.63 cm), and concluded that in addition to the fact that statin treatment is efficacious, the results support the notion that statin treatment in children is safe. A multicenter, randomized, double-blind, placebo-controlled study of 173 children (de Jongh 2002) was conducted to evaluate LDL cholesterol lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia. After a 4-week diet/placebo run-in period, subject were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. Simvastatin significantly reduced LDL cholesterol, total cholesterol, triglyceride, VLDL cholesterol, and apolipoprotein B levels at 48 weeks of study, and was well tolerated in children with hefh. There was no evidence of any adverse effect of simvastatin on growth and pubertal development. The authors concluded that simvastatin at doses up to 40 mg is a well-tolerated and effective therapy for hefh children. Policy updates: A Cochrane systematic review (Vuorio 2017) evaluated the long-term safety of statin use in the pediatric 5

6 age group of children with heterozygous familial hypercholesterolemia (n=1177). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence). The authors concluded that statin treatment is an effective and safe lipid-lowering therapy in children with familial hypercholesterolemia. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Summary of clinical evidence: Citation Vuorio (2017 Statins for children with familial hypercholesterolemia. Pencina (2014) Content, Methods, Recommendations A systematic review evaluated the long-term safety of statin use in the pediatric age group of children with heterozygous familial hypercholesterolemia (n=1177). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence). The authors concluded that statin treatment is an effective and safe lipid-lowering therapy in children with familial hypercholesterolemia. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Hypercholesterolemia- -a disease with expression from childhood A systematic review to assess the effects, both in terms of benefits and harms of statins, for the primary prevention of CVD found 18 randomized controlled trials with 19 trial arms (56,934 patients) dating from 1994 to All were randomized control trials comparing statins with usual care or placebo. The mean age of the participants was 57 years (range years), 60.3% were men, 6

7 Citation Content, Methods, Recommendations and of the eight trials that reported on ethnicity, 85.9 % were Caucasian. Duration of treatment was a minimum one year and with follow-up of a minimum of six months. All-cause mortality and fatal and non-fatal CVD events were reduced with the use of statins as was the need for revascularization (the restoration of an adequate blood supply to the heart) by means of surgery (coronary artery bypass graft ) or by angioplasty (PTCA). Of 1000 people treated with a statin for five years, 18 would avoid a major CVD event which compares well with other treatments used for preventing cardiovascular disease. Taking statins did not increase the risk of serious adverse effects such as cancer. Statins are likely to be cost-effective in primary prevention. Huffman (2013) Statins for the primary prevention of cardiovascular disease ACC-AHA (2013) ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults Eighteen randomised control trials (19 trial arms; 56,934 participants) were included. Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and nonfatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularization rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be costeffective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event. The 2013 guidelines of the American College of Cardiology and the American Heart Association (ACC-AHA) for the treatment of cholesterol expand the indications for statin therapy for the prevention of cardiovascular disease. Using data from the National Health and Nutrition Examination Surveys of 2005 to 2010, ACC-AHA estimated the number, and summarized the risk-factor profile, of persons for whom statin therapy would be recommended. Under the new ACC-AHA guidelines there is an estimated population of million U.S. adults between the ages of 40 and 75 years who may benefit from this treatment. In many cases, indication would exist among adults without clinically overt cardiovascular disease. Among adults between the ages of 60 and 75 years without cardiovascular disease who are not receiving statin therapy, the percentage for whom such therapy would be indicated may increase from 30.4% to 87.4% among men and from 21.2% to 53.6% among women. This effect would be driven largely by an increased number of adults who would be classified solely on the basis of their 10-year risk of a cardiovascular event. 7

8 Citation Desai (2012) A systematic review and meta-analysis of statin therapy in children with familial hypercholesterolemia Espinheira (2013) Initiation of statin therapy Vuorio (2014) Content, Methods, Recommendations Those who would be newly eligible for statin therapy include more men than women and persons with a higher blood pressure but a markedly lower level of low-density lipoprotein cholesterol. The new guidelines recommend statin therapy for more adults who would be expected to have future cardiovascular events (higher sensitivity) but would also include many adults who would not have future events (lower specificity). Only a few studies of statin use have included older individuals, particularly ages 80 years or older. A recent narrative review of statin in this population found the association of adverse effects with intensive doses of statin and their interactions with other drugs may be more problematic in older adults. Statin therapy appears cost-effective for individuals with higher CVD risk but this is dependent on the assumptions used. The authors concluded that evidence remains limited regarding the overall benefit of starting statin therapy in adults ages 80 years and older; thus, clinical judgment remains necessary in making this decision. A randomized controlled trial of a total of 168 children found that forty-six presented a familial hypercholesterolemia phenotype, and in 22 of these, a mutation in the low-density lipoprotein (LDL) receptor gene was identified. The lipid profile of the group with mutations showed significantly higher values of total and non-high-density lipoprotein (HDL) cholesterol compared to the group without mutations (total cholesterol 316.5±75.9 mg/dl vs ±42,0 mg/dl; non-hdl cholesterol 268.3±72.6 mg/dl vs ±43.9 mg/dl; p<0.05). Of the total, 55 were prescribed pharmacological therapy and the others underwent diet and exercise interventions only. A greater reduction in LDL cholesterol was observed in individuals under pharmacological therapy compared to those prescribed diet and exercise only (30.3% vs. 18.1%). The evidence suggests that hypercholesterolemia is associated with the atherosclerotic process from childhood, and that pediatric hypercholesterolemia justifies the screening of high-risk children and initiation of therapy at preschool ages. Statins for children A systematic review of 21 studies, of which eight were randomized placebo-controlled studies (1074 participants),) found that statins reduced the mean LDL cholesterol concentration at all time points from six weeks to two years. The risks of myopathy and clinical adverse events were very low in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery, and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness. The authors concluded that statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified; however, long-term safety is unknown. 8

9 Citation Avis (2007) Efficacy and Safety of Statin Therapy in Children de Jongh (2002) Content, Methods, Recommendations A systematic review and meta-analysis of statin therapy in children with familial hypercholesterolemia aged 8 to 18 years examined six pertinent studies (n=798 children) inclusive of 12 to 104 weeks of treatment. Total cholesterol, LDL cholesterol, and apolipoprotein B were significantly reduced, whereas HDL cholesterol and apolipoprotein A1 were significantly increased by statin therapy. No statistically significant differences were found between statin- and placebo-treated children with respect to the occurrence of adverse events (RR 0.99; 95% CI: 0.79 to 1.25), sexual development (RR of advancing > or = 1 stage in Tanner classification 0.96; 95% CI: 0.79 to 1.17), muscle toxicity (RR of CK > or = 10 times the upper limit of normal [ULN] 1.38; 95% CI: 0.18 to 10.82), or liver toxicity (RR of > or = 3 times the ULN for ASAT 0.98; 95% CI: 0.23 to 4.26 and for ALAT 2.03; 95% CI: 0.24 to 16.95). The authors found a minimal difference in growth in favor of the statin group (0.33 cm; 95% CI: 0.03 cm to 0.63 cm), and concluded that in addition to the fact that statin treatment is efficacious, the results support the notion that statin treatment in children is safe. Efficacy and Safety of Statin Therapy in Children A multicenter, randomized, double-blind, placebo-controlled study of 173 children was conducted to evaluate LDL cholesterol lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia. After a 4-week diet/placebo run-in period, subject were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. Simvastatin significantly reduced LDL cholesterol, total cholesterol, triglyceride, VLDL cholesterol, and apolipoprotein B levels at 48 weeks of study, and was well tolerated in children with hefh. There was no evidence of any adverse effect of simvastatin on growth and pubertal development. The authors concluded that simvastatin at doses up to 40 mg is a welltolerated and effective therapy for hefh children. References Professional society guidelines/other: Stone NJ, Robinson J, Lichtenstein AH, et al ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;11:1 84. Peer-reviewed references: 9

10 Avis H, Vissers MN, Stein EA, Wijburg FA, Trip MD, Kastelein JJ, Hutten BA. Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2007;27(8): de Jongh S, Ose L, Szamosi T, et al. Application of new cholesterol guidelines to a population-based sample: Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia Circulation. 2002;106: Desai DA, Zakaria S, Ouyang P. A systematic review and meta-analysis of statin therapy in children with familial hypercholesterolemia. Curr Atheroscler Rep. 2012;14(1): Espinheira M, Vasconcelos C, Medeiros AM, Alves AC, Bourbon M, Guerra A. Initiation of statin therapy: are there age limits? Rev Port Cardiol. 2013;32(5): Huffman T, Macedo AF, Moore T, et al. Randomized, Double-Blind, Placebo-Controlled Trial With Simvastatin: Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD Pencina MJ, Navar-Boggan AM, D'Agostino RB Sr, Williams K, Neely B, Sniderman AD, et al. Hypercholesterolemia--a disease with expression from childhood. N Engl J Med. 2014;370(15): Vuorio A, Kuoppala J, Kovanen PT, et al. Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev Jul 23;7:CD Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Tonstad S, Wiegman A, Drogari E, Ramaswami U. Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev Jul 7;7:CD CMS National Coverage Determination (NCDs): No NCDs identified as of the writing of this policy. Local Coverage Determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill in accordance with those manuals. 10

11 CPT Code Description Comment 4013F Statin therapy prescribed or currently being taken (CAD) ICD-10 Code Description Comment E78.01 Familial hypercholesterolemia E78.00 Pure hypercholesterolemia, unspecified HCPCS Level II Code G9664 G9963 G9966 Description Patients who are currently statin therapy users or received an order (prescription) for statin therapy Any fasting or direct LDL-C laboratory test result = 190 mg/dl The highest fasting or direct LDL-C laboratory test result of 70/189 mg/dl in the measurement period or two years prior to the beginning of the measurement period Comment 11