Premera Bluecross high cholesterol Coverage Update | OpenPayer
ModifiedPremera BluecrossPolicy N/A
Pharmacologic Treatment of High Cholesterol — Coverage Criteria
Defines medical necessity criteria for several non-statin lipid-lowering therapies (PCSK9 inhibitors, inclisiran, icosapent ethyl/Vascepa and generics, Lovaza, bempedoic acid products, evinacumab, olezarsen) for adults and some pediatric indications; intended for providers prescribing these agents.
Policy Summary
PayerPremera Bluecross
PolicyPharmacologic Treatment of High Cholesterol — Coverage Criteria
Policy CodePolicy N/A
Change TypeMultiple material updates (added Tryngolzarevised Evkeeza ageremoved some re-auth requirements)
Effective DateApr 8, 2025
Next Review DateN/A
Key ActionObtain prior authorization with documentation of age, prescriber specialty, qualifying diagnosis, required prior high-intensity statin trial (or documented intolerance), and relevant lipid levels per agent-specific criteria.
Added coverage criteria for Tryngolza (olezarsen) for the treatment of familial chylomicronemia syndrome.
Updated Evkeeza (evinacumab-dgnb) coverage criteria age requirement from 12 years to 5 years of age and older.
Updated coverage criteria for Leqvio (inclisiran), Repatha (evolocumab), Praluent (alirocumab), Nexletol (bempedoic acid) and Nexlizet to include treatment of certain adults with primary hyperlipidemia.
Added coverage criteria for Tryngolza (olezarsen) for the treatment of familial chylomicronemia syndrome.
Removed re-authorization requirement to continue using a maximum tolerated statin from Evkeeza, Juxtapid, Leqvio, Nexletol, Nexlizet, Praluent, and Repatha.
Updated Evkeeza coverage age requirement from 12 years to 5 years and older and updated other age/step-therapy and diagnostic criteria across agents including Leqvio, Repatha, Praluent, Nexletol, and Nexlizet.
Added coverage criteria for Tryngolza (olezarsen) and added HCPCS code J3490 to policy to report Tryngolza.
Added coverage for Atorvaliq (atorvastatin oral suspension) for the treatment of hyperlipidemia.
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multipledrug classes covered
70–400+LDL-C thresholds referenced
59%max LDL-C reduction (evolocumab)
−52%inclisiran mean LDL change
pharmacy/medicalmanagement split
J3490Tryngolza coding update
Medical Necessity and Coverage Criteria
Repatha (evolocumab) — ASCVD
Repatha may be considered medically necessary when ALL of the following are met:
ALL of the following
Age: Individual is aged 18 years or olderage >=18
Prescriber: Prescribed by or in consultation with a cardiologist, endocrinologist, or a physician who focuses on cardiovascular risk management or lipid disorders
ASCVD history: Individual has prior myocardial infarction, acute coronary syndrome, angina (stable or unstable), prior stroke or transient ischemic attack, peripheral arterial disease of atherosclerotic origin, or prior coronary/arterial revascularization (e.g., CABG, PCI, angioplasty, stent)
examples listed
Statin trial or intolerance: Has tried one high-intensity statin (e.g., atorvastatin >=40 mg daily or rosuvastatin >=20 mg daily) for at least 8 continuous weeks AND LDL-C remains >=70 mg/dL OR is statin intolerant as demonstrated by rhabdomyolysis to one statin or muscle symptoms after trying both rosuvastatin and atorvastatin which resolved on discontinuationstatin trial >=8 weeks or documented intolerance
Dose limited to 140 mg every 2 weeks OR 420 mg (monthly dosing option) per product dosing guidance
Praluent may be considered medically necessary when ALL of the following are met (note: generally requires prior Repatha trial/intolerance):
ALL of the following
Age (ASCVD): Individual is aged 18 years or older for ASCVD and primary hyperlipidemia indicationsage >=18
Repatha prior: Has tried Repatha (evolocumab) first and had inadequate response or intolerance to Repatha (step therapy requirement)
Step therapy requirement
Prescriber: Prescribed by or in consultation with a cardiologist, endocrinologist, or a physician who focuses on cardiovascular risk management or lipid disorders
Leqvio (inclisiran) — PCSK9 siRNA
Leqvio may be considered medically necessary when ALL of the following are met (generally requires prior Repatha trial/intolerance):
ALL of the following
Age: Individual is aged 18 years or older for ASCVD and primary hyperlipidemia indicationsage >=18
Repatha prior: Has tried Repatha (evolocumab) first and had an inadequate response or intolerance to Repatha
Step therapy requirement
Prescriber: Prescribed by or in consultation with a cardiologist, endocrinologist, or physician focusing on cardiovascular risk/lipid disorders
Icosapent ethyl (Vascepa and generic) and Lovaza — ASCVD and severe hypertriglyceridemia
Icosapent ethyl (Vascepa/generic) may be considered medically necessary for ASCVD risk reduction and for severe hypertriglyceridemia when ALL listed criteria are met:
Nexletol and Nexlizet may be considered medically necessary for ASCVD, HeFH, and primary hyperlipidemia when ALL of the following are met:
ALL of the following
Age: Individual is aged 18 years or olderage >=18
ASCVD history: Meets ASCVD history criteria (prior MI, ACS, angina, prior stroke/TIA, PAD of atherosclerotic origin, or prior arterial revascularization)
examples listed
Statin trial or intolerance: Has tried one high-intensity statin (atorvastatin >=40 mg or rosuvastatin >=20 mg) for >=8 continuous weeks and LDL-C remains >=70 mg/dL OR is statin intolerant as demonstrated by rhabdomyolysis or muscle symptoms after trying both rosuvastatin and atorvastatin which resolved on discontinuation
Lovaza — severe hypertriglyceridemia
Covered when ALL of the following are met
Lovaza criteria: The individual is aged 18 years or older AND fasting TG >=500 mg/dL AND has tried and failed one fibrate (fenofibrate, fenofibric acid, gemfibrozil) OR has tried and failed prescription niacin ER OR has had trial/failure/intolerance to generic omega-3-acid ethyl esters when applicable AND the daily dose is 4 grams per day. Initial approval: 3 years; re-authorization: 3 years with chart notes documenting continued clinical benefit.TG >=500 mg/dL
Alternative pathway permits trial/failure or intolerance to generic omega-3-acid ethyl esters.
Nexletol / Nexlizet coverage sets
Covered when ALL of the following are met
ASCVD indication: Age >=18 AND history of ASCVD (prior MI/ACS, angina, prior stroke/TIA, PAD of atherosclerotic origin, prior arterial revascularization) AND tried one high-intensity statin (atorvastatin >=40 mg or rosuvastatin >=20 mg daily for >=8 weeks) and LDL-C remains >=70 mg/dL OR is statin intolerant as defined (rhabdomyolysis or muscle symptoms after trials of rosuvastatin and atorvastatin resolving on discontinuation).LDL-C >=70 mg/dL
Statin intolerance criteria explicit.
HeFH indication: Age >=18 AND meets genetic or diagnostic HeFH criteria (untreated LDL-C >=190 mg/dL or genetic confirmation or clinical diagnostic criteria) AND trial of one high-intensity statin >=8 weeks with LDL-C >=70 mg/dL OR statin intolerance as defined.LDL-C >=190 mg/dL or genetic confirmation
Dutch Lipid Network, Simon Broome criteria referenced.
Evkeeza (HoFH): Individual is aged 5 years or older AND prescribed by or in consultation with a cardiologist, endocrinologist, or physician focusing on lipid disorders AND has tried Repatha (evolocumab) first and had inadequate response or intolerance AND either untreated LDL-C >400 mg/dL OR treated LDL-C >=300 mg/dL AND genetic confirmation of two mutant alleles at LDLR/APOB/PCSK9/LDLRAP1 locus AND trial of a high-intensity statin >=8 continuous weeks with LDL-C >=70 mg/dL OR statin intolerance as defined.untreated LDL-C >400 mg/dL or treated LDL-C >=300 mg/dL
Specialist involvement and prior PCSK9 therapy required; dosing and efficacy supported by ELIPSE-HoFH trial.
Tryngolza — familial chylomicronemia syndrome
Covered when ALL of the following are met
Tryngolza (FCS): Individual is aged 18 years or older AND genetic confirmation of familial chylomicronemia syndrome (FCS) AND history of and current adherence to strict dietary management (<20 g fat/day; avoidance of sugar and alcohol) AND confirmed fasting triglyceride >=880 mg/dL while under strict dietary management AND dose limited to 80 mg once monthly AND prescribed by or in consultation with a cardiologist, endocrinologist, gastroenterologist, lipidologist, or pancreatologist.fasting TG >=880 mg/dL
Specialist prescriber and dietary management required; efficacy shown in BALANCE trial
Juxtapid (HoFH): Individual is aged 18 years or older AND has tried Repatha (evolocumab) first with inadequate response or intolerance AND either untreated LDL-C >=400 mg/dL OR treated LDL-C >=300 mg/dL AND genetic confirmation of two mutant alleles at LDLR/APOB/PCSK9/LDLRAP1 locus AND trial of a high-intensity statin >=8 continuous weeks with LDL-C >=70 mg/dL OR statin intolerance as defined AND dose limited to 60 mg daily.dose <=60 mg daily; LDL thresholds as specified
Specialist prescriber referenced for related agents.
Brand statins / fibrates — trial requirements
Covered when ALL of the following are met
Brand statin/fibrate criteria: Brand statins or brand formulations may be considered medically necessary when the individual has had a trial and treatment failure or intolerance to TWO generic statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin). Initial approval generally for 3 years; re-authorization based on documented continued clinical benefit (e.g., at-goal LDL-C).
Oral suspension formulations require documentation of clinical necessity or trial failure.
Statin intolerance — myalgias and transaminitis
Covered when ALL of the following are met
Myalgias-related statin intolerance: Individual has intolerable muscle symptoms (myalgias) and provider has ruled out other potential causes (e.g., interacting medications, hypothyroidism, renal or hepatic dysfunction, steroid myopathy, vitamin D deficiency, primary muscle disease).
Must be in addition to meeting other criteria for alternative therapies.
Transaminitis-related statin intolerance: Provider ruled out other causes for transaminitis; transaminitis persists beyond 12 weeks from statin initiation AND individual failed reduction of statin therapy.
Required for consideration of alternative therapy due to transaminitis.
Conceptual coverage criteria for PCSK9-targeted therapy
Covered when ALL of the following are met (conceptually):
Background therapy: Patient is on maximally tolerated statin therapy (with or without other lipid-modifying therapy)maximally tolerated statin
Persistent LDL-C elevation: Patient requires additional LDL-C lowering despite maximally tolerated statin therapye.g., LDL-C thresholds vary by indication (commonly >=70 mg/dL for ASCVD/HeFH; >=100 mg/dL for primary hyperlipidemia)
Specific numeric cutoffs are provided in individual product sections; document baseline LDL-C and need for further lowering.
Indication groups studied: Patient has clinical ASCVD OR heterozygous familial hypercholesterolemia (HeFH) OR homozygous familial hypercholesterolemia (HoFH) as appropriate per product-specific criteria
Evidence-based coverage populations
Evidence summaries that could form the basis for coverage criteria:
Inclisiran (Leqvio) efficacy: Trials (ORION-10, ORION-11, ORION-9) enrolled adults on maximally tolerated statin therapy requiring additional LDL-C lowering and demonstrated placebo-corrected LDL-C reductions of ~48%–52% at day 510 (18 months). Trials excluded individuals taking PCSK9 inhibitors.LDL-C reduction ~48–52% observed
Document statin use and absence of concurrent PCSK9 inhibitor therapy in authorization.
Icosapent ethyl (Vascepa) efficacy: REDUCE-IT showed 4 g/day icosapent ethyl reduced 5-point MACE by 25% and 3-point MACE by 26% in a high-risk population with baseline LDL-C and TG ranges, supporting use for ASCVD risk reduction when trial criteria are met.
Trials required background statin use and specific TG/LDL ranges.
Bempedoic acid (Nexletol) efficacy: CLEAR program showed placebo-corrected LDL reductions around ~17–21% at week 12 across populations including ASCVD/HeFH and statin-intolerant groups, supporting use as additional LDL-lowering therapy.
Evkeeza (evinacumab) — trial evidence
Coverage-supporting clinical findings for Evkeeza (evinacumab):
Evkeeza efficacy summary: ELIPSE-HoFH showed evinacumab 15 mg/kg IV every 4 weeks produced a 47.1% reduction from baseline in LDL-C at week 24 versus placebo, consistent across background therapies; 84% had >30% LDL reduction and 56% had >50% reduction, with an absolute mean LDL change of -134.7 mg/dL (±12.4).
Supports coverage for HoFH with updated age allowance to >=5 years.
Tryngolza (olezarsen) — trial evidence
Coverage-supporting clinical findings for Tryngolza (olezarsen) in familial chylomicronemia syndrome (FCS):
Tryngolza primary efficacy: The Phase III BALANCE trial in genetically confirmed FCS (fasting TG >=880 mg/dL) showed olezarsen 80 mg SC every 4 weeks produced a least-squares mean % reduction in fasting TG at 6 months vs placebo of -43.5% (P<0.001) and -59.4% vs placebo at 12 months, supporting the approved indication as adjunct to diet for adults with FCS.fasting TG >=880 mg/dL for enrollment
Tryngolza impact on pancreatitis: Pooled olezarsen groups had a much lower mean rate ratio for acute pancreatitis events vs placebo (mean rate ratio 0.12; 95% CI 0.02–0.66), although this was a secondary endpoint and hierarchical testing limits formal statistical claims.
Supports clinical benefit signal for pancreatitis reduction.
The Introduction provides clinical context only and is not itself a set of coverage rules. It explains that familial hypercholesterolemia (FH) is a genetic disorder leading to markedly elevated LDL-C and increased atherosclerotic cardiovascular risk and notes that lifestyle measures and statins are first-line therapy. The policy's Medical Necessity sections that follow contain the explicit coverage criteria for non‑statin lipid‑lowering agents; this Introduction should be used only for background understanding and not as authorization criteria.
Per the policy, all uses of the listed drugs for indications not specified in the Medical Necessity sections are considered not medically necessary. Requests for therapies or indications outside the explicit Medical Necessity criteria may be denied and should not be submitted as covered indications.
The pivotal inclisiran (LEQVIO) trials (ORION programs) enrolled patients who were taking maximally tolerated statin therapy and explicitly excluded individuals actively receiving PCSK9 monoclonal antibodies. Protocol language in ORION‑10, ORION‑11, and ORION‑9 describes this exclusion.
Because multiple inclisiran trials excluded concurrent PCSK9 inhibitor use, the absence of trial data in patients already receiving PCSK9 monoclonal antibodies represents an evidence gap. The policy notes that trial exclusions for PCSK9 inhibitor users may affect coverage decisions and requests involving these clinical scenarios should include rationale and supporting data.
Evkeeza (evinacumab) carries warnings for serious hypersensitivity reactions and for potential embryo‑fetal toxicity. The prescribing information recommends obtaining a pregnancy test prior to initiating therapy and counseling on contraception for individuals who may become pregnant; consider discontinuation and monitoring if a serious hypersensitivity reaction occurs.
This medical policy document does not apply to Medicare Advantage. Providers and members should consult the member benefit booklet or contact customer service for benefit‑specific coverage determinations under Medicare Advantage plans.
The coverage criteria sections specify the individual products addressed by this policy (for example, Repatha, Praluent, Leqvio, Evkeeza, Nexletol/Nexlizet, Vascepa/icosapent ethyl, Lovaza, Tryngolza, Juxtapid) and the HCPCS codes used for some injectable specialty agents (e.g., J1305 for evinacumab, J1306 for inclisiran, and J3490 for unclassified drugs such as Tryngolza where applicable).
The policy designates therapies as not medically necessary when used for indications lacking evidence of LDL‑C or triglyceride benefit or when no additional LDL‑C reduction beyond maximally tolerated statin therapy is required. In short, use in indications without demonstrated LDL‑C lowering benefit or without need for further LDL‑C reduction is not supported by the trial evidence summarized in the policy.
Because of animal and clinical safety findings, treatment with evinacumab during pregnancy is cautioned. The policy states that initiating Evkeeza in pregnancy is not supported by trial safety data; pregnancy testing prior to initiation and counseling on contraception during treatment (and for a recommended period after last dose) are advised.
For pitavastatin (Livalo), the policy notes that there is no evidence of clinical superiority for pitavastatin over other statins in most individuals and that its brand‑only availability may influence cost‑based coverage decisions; this supports the policy position to require trials of generic alternatives before covering brand formulations.
Billing and Coding
No CPT/HCPCS/ICD codes listed in this excerptmixed
No codes listed
HCPCS codesHCPCS
J1305
Injection, evinacumab-dgnb, (Evkeeza) 5 mg.
J1306
Injection, inclisiran; (Leqvio) mg.
J3490
Unclassified drugs (use to report: Tryngolza)
Covered CPT/HCPCS/NDC codes (not listed in this excerpt)mixed
No codes listed
HCPCS codes mentioned in history/coding updatesHCPCS
J3490
HCPCS code used to report Leqvio/Tryngolza (noted added/removed then re-added)
J1305
HCPCS code previously added (coding update noted in history)
Prior Authorization, Documentation, and Step Therapy
Prior Authorization
Prior Authorization Required for Listed Lipid Agents
Prior authorization is required for all listed lipid-modifying agents in this policy (PCSK9 inhibitors, inclisiran/Leqvio, evinacumab/Evkeeza, bempedoic acid/Nexletol, Nexlizet, lomitapide/Juxtapid, icosapent ethyl/Vascepa, omega-3 preparations, and other specialty lipid agents). Prescribers should submit a prior authorization request before initiating therapy to avoid delays or denials.
Applies to: Repatha (evolocumab), Praluent (alirocumab), Leqvio (inclisiran), Evkeeza (evinacumab-dgnb), Nexletol (bempedoic acid), Nexlizet (bempedoic acid + ezetimibe), Juxtapid (lomitapide), Vascepa (icosapent ethyl), Lovaza (omega-3-acid ethyl esters), and other agents specified in policy.
Non-formulary exception requests may be considered (see prescribing information and benefit plan limits).
Prior Authorization
Prior Authorization: Background Therapy and Exclusion
Prior authorization approvals are contingent on meeting background therapy and exclusion criteria documented in the coverage criteria. Many agents require prior trials of statins or other lipid-lowering therapies, and some require trials of specific biologic agents (e.g., PCSK9 inhibitors) before alternatives are authorized. Trials excluded from clinical studies (for example, participants using PCSK9 inhibitors in ORION/LEQVIO trials were excluded) may affect coverage expectations.
Key Definitions and Diagnostic Criteria
Familial hypercholesterolemia (FH)
DefinitionA genetic disorder causing inability to remove LDL cholesterol from blood resulting in very high LDL and increased risk of atherosclerotic cardiovascular disease (FH)
PathophysiologyCaused by defects in genes of the LDL receptor pathway leading to markedly elevated LDL-C and premature atherosclerosis
Initial managementLifestyle modification and statin therapy are first-line; non‑statin agents considered when LDL/TG thresholds persist or statin intolerance exists
Definite Familial Hypercholesterolemia
Numeric criteria (children/adults)Definite FH: child LDL‑C ≥155 mg/dL or total cholesterol >260 mg/dL; adult LDL‑C ≥190 mg/dL or total cholesterol ≥290 mg/dL
Clinical signs
Policy Revision History
08/05/2015policy_created
New policy created and added to Pharmacy subsection to cover adjunctive use with diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or clinical ASCVD when criteria are met.
12/01/2018annual_review
Annual review completed; literature search and summary of FOURIER and ODYSSEY outcomes trials added with no change to criteria.
04/01/2019interim_update
Policy Summary
PayerPremera Bluecross
PolicyPharmacologic Treatment of High Cholesterol — Coverage Criteria
Policy CodePolicy N/A
Change TypeMultiple material updates (added Tryngolzarevised Evkeeza ageremoved some re-auth requirements)
Effective DateApr 8, 2025
Next Review DateN/A
Key ActionObtain prior authorization with documentation of age, prescriber specialty, qualifying diagnosis, required prior high-intensity statin trial (or documented intolerance), and relevant lipid levels per agent-specific criteria.
ASCVD history: Individual has prior myocardial infarction, acute coronary syndrome, angina, prior stroke/TIA, PAD of atherosclerotic origin, or prior coronary/arterial revascularization
examples listed
Statin trial or intolerance: Has tried one high-intensity statin (e.g., atorvastatin >=40 mg daily or rosuvastatin >=20 mg daily) for at least 8 continuous weeks AND LDL-C remains >=70 mg/dL OR is statin intolerant as defined (rhabdomyolysis or muscle symptoms after trials of rosuvastatin and atorvastatin resolving on discontinuation)
Dose limited to 150 mg every 2 weeks OR 300 mg monthly per product dosing guidance
documented dosing limits in policy
ALL of the following
Age (HeFH): Individual is aged 8 years or older for heterozygous familial hypercholesterolemia (HeFH)age >=8
Repatha prior: Has tried Repatha first and had inadequate response or intolerance to Repatha
HeFH criteria: Untreated LDL-C >=190 mg/dL OR genetic confirmation of HeFH (LDLR, APOB, PCSK9, LDLRAP1) OR Dutch Lipid Network score >=5 OR Simon Broome criteria 'definite' or 'possible'LDL-C >=190 mg/dL or genetic/clinical criteria
Statin trial or intolerance: Tried one high-intensity statin >=8 weeks and LDL-C remains >=70 mg/dL OR statin intolerant as defined
Dose limited to 150 mg every 2 weeks OR 300 mg monthly
ALL of the following
HoFH age: Individual is aged 18 years or older for HoFH per excerptage >=18
Repatha prior: Has tried Repatha first and had inadequate response or intolerance to Repatha
HoFH criteria: Untreated LDL-C >=400 mg/dL OR treated LDL-C >=300 mg/dL OR genetic confirmation of two mutant alleles at LDLR/APOB/PCSK9/LDLRAP1 locusLDL-C >=400 untreated or >=300 treated or 2 mutant alleles
Statin trial or intolerance: Tried one high-intensity statin >=8 weeks and LDL-C remains >=70 mg/dL OR statin intolerant
Dose limited to 150 mg every 2 weeks
ASCVD history: Individual has prior MI, ACS, angina, prior stroke/TIA, PAD of atherosclerotic origin, or prior coronary/arterial revascularization
Document and confirm statin use and absence of concurrent PCSK9 inhibitor use
Dose schedule: 284 mg at initiation, at 3 months, then every 6 months thereafter284 mg loading then q6 months
ALL of the following
HeFH criteria (Leqvio): Untreated LDL-C >=190 mg/dL OR genetic confirmation OR Dutch Lipid Network score >=5 OR Simon Broome 'definite/possible'LDL-C >=190 or genetic/clinical criteria
Statin trial or intolerance: Tried high-intensity statin >=8 weeks and LDL-C remains >=70 mg/dL OR statin intolerant
Risk/ASCVD criteria: Has established cardiovascular disease OR diabetes mellitus plus two additional specified risk factors (family history of premature ASCVD, tobacco use, hypertension defined as BP >=130/80 on antihypertensive, renal dysfunction, age thresholds)
Risk factors detailed in policy
Prior generic trial: Has had a trial and treatment failure or intolerance to generic icosapent ethyl before Vascepa (where applicable)
Dose is 4 grams per day (four 0.5-g capsules twice daily or two 1-g capsules twice daily)4 g/day
ALL of the following
Severe TG age: Individual is aged 18 years or olderage >=18
Prior fibrate/niacin trial: Has tried and failed one fibrate (fenofibrate, fenofibric acid, gemfibrozil) OR prescription niacin ER
Prior generic icosapent ethyl: Has had trial and treatment failure or intolerance to generic icosapent ethyl (when Vascepa requested)
Dose is 4 grams per day4 g/day
ALL of the following
Lovaza severe TG: For Lovaza: age >=18 AND TG >=500 mg/dL AND trial/failure of a fibrate or niacin ER OR trial/failure/intolerance to generic omega-3-acid ethyl esters AND daily dose 4 g/day; initial approval 3 years with reauthorization based on documented continued clinical benefitTG >=500 mg/dL
Prescriber: Prescribed by or in consultation with a cardiologist, endocrinologist, or lipid-focused physician
ALL of the following
HeFH indication: For HeFH: individual aged >=18 AND meets HeFH criteria (untreated LDL-C >=190 mg/dL or genetic confirmation or diagnostic criteria) AND trial of one high-intensity statin >=8 weeks with LDL-C >=70 mg/dL OR statin intolerance as definedLDL-C >=190 mg/dL or genetic confirmation
Dutch Lipid Network and Simon Broome referenced
ALL of the following
Primary hyperlipidemia: Age >=18 AND CAC >=100 Agatston units or >=75th percentile for age/gender/ethnicity OR 10-year ASCVD risk >=7.5% OR diabetes AND tried one high-intensity statin >=8 weeks with LDL-C remains >=100 mg/dL OR statin intolerantLDL-C >=100 mg/dL or ASCVD risk >=7.5%
Documented thresholds provided in policy
Age >=18 AND elevated CAC or 10-year ASCVD risk >=7.5% or diabetes AND tried one high-intensity statin >=8 weeks with LDL-C remains >=100 mg/dL OR statin intolerance as defined.
10-year ASCVD risk >=7.5% or CAC >=100 Agatston units
Documented thresholds provided in policy.
diagnosis per clinical or genotyping criteria
Trials informing these criteria included ASCVD, HeFH, and HoFH populations for PCSK9-targeted therapies.
Evinacumab (Evkeeza) efficacy: ELIPSE-HoFH demonstrated ~47% mean LDL-C reduction at 24 weeks versus placebo when added to maximal tolerated therapy, with 84% achieving >30% LDL reduction and 56% >50% reduction, supporting coverage in HoFH per criteria.~47% LDL reduction at 24 weeks
Requires documentation of HoFH diagnosis and background therapy.
Initial and early dosingSingle 284 mg subcutaneous injection at initiation and again at 3 months
Maintenance dosingThen 284 mg every 6 months thereafter
MonitoringAssess LDL-C when clinically indicated; effect measurable as early as 30 days
Repatha dosing limits
Standard dosing (primary hyperlipidemia/ASCVD/HeFH)Evolocumab 140 mg subcutaneous every 2 weeks or 420 mg once monthly
HoFH dosingFor homozygous FH the recommended dose is 420 mg once monthly (administer as three REPATHA injections consecutively within 30 minutes)
Dose monitoringMeasure LDL-C to assess response after initiation or titration (per trials and prescribing information)
Praluent dosing limits
Typical dosingAlirocumab 75 mg SQ every 2 weeks is starting dose; increase if inadequate response
Documented dose limitsDose limited to 150 mg every 2 weeks (maximum) or 300 mg every month (per policy dosing statements)
Dose adjustment guidanceMeasure LDL-C within 4–8 weeks of initiation or titration and adjust dose if needed
Icosapent ethyl dosing
Daily total dose4 grams per day
Capsule regimensEither four 0.5‑g capsules twice daily with food or two 1‑g capsules twice daily with food
Indication contextsUsed for ASCVD risk reduction and for treatment of severe hypertriglyceridemia when criteria met
Add-on LDL-C threshold (general)LDL-C ≥70 mg/dL when additional LDL lowering is required despite high-intensity statin
HoFH thresholds referencedUntreated LDL-C >400 mg/dL or treated LDL-C ≥300 mg/dL for HoFH-related therapies
LDL-C thresholds for FH/classification
Child diagnostic thresholdChild: LDL‑C ≥155 mg/dL or total cholesterol >260 mg/dL (≤16 years)
Adult diagnostic thresholdAdult: LDL‑C ≥190 mg/dL (≥4.9 mmol/L) or total cholesterol ≥290 mg/dL
Use in clinical criteriaThese numeric thresholds are used within Simon Broome/Dutch Lipid Network definitions to classify FH
Dutch Lipid Network scoring thresholds
Definite FHDutch Lipid Network score >8
Probable FHScore 6–8
Possible FHScore 3–5
Unlikely FHScore <3
Fasting triglyceride entry threshold for BALANCE trial enrollment
BALANCE trial enrollmentFasting triglyceride ≥880 mg/dL for genetically confirmed FCS
Diagnosis requirementGenetic confirmation of familial chylomicronemia syndrome required for enrollment/indication
Dietary management contextEnrollment occurred while patients were under strict dietary management (<20 g fat/day)
re-authorization length
Typical initial approval length (historic)Initial approval for some oral formulations (e.g., Ezallor Sprinkle, Livalo, Zypitamag) was 3 years
Lovaza specific initial/re-authorizationLovaza initial approval 3 years; re-authorization approved for 3 years with chart documentation of continued clinical benefit
Recent changesPolicy history notes removal of some re-authorization requirements for multiple agents in later updates
Background therapy: maximally tolerated statin therapy is generally required where specified; some indications require concomitant ezetimibe or other agents per drug-specific criteria.
Exclusions: Individuals who meet trial exclusion criteria referenced in pivotal studies (e.g., active PCSK9 inhibitor use during inclisiran trials) should have documentation explaining applicability to the current request.
Step Therapy
Prior Authorization and Step Changes
Step therapy and prior-authorizations have been updated in recent policy revisions. Providers must follow the current step requirements (e.g., Repatha-first requirement changed for certain agents; Evkeeza and Juxtapid step requirements were changed to require Repatha prior trial only). Requests that do not document required step(s) risk denial.
2024–2025 updates: Evkeeza and Juxtapid step therapy requirement updated from Praluent + Repatha to Repatha only; Repatha age requirements changed; Praluent pediatric age updated.
Document prior biologic/generic trials per policy version in effect at time of request.
Prior Authorization
Prior Statin Therapy or Intolerance Required
Most PCSK9 and other specialty lipid therapies require prior statin therapy unless the member is statin-intolerant. Statin intolerance must be documented (see required medical record documentation).
Required evidence: trial of a high-intensity statin (e.g., atorvastatin ≥40 mg or rosuvastatin ≥20 mg) for at least 8 continuous weeks unless intolerant.
If statin-intolerant, document rhabdomyolysis to one statin or skeletal-muscle symptoms after trials of both rosuvastatin and atorvastatin that resolved on discontinuation.
Denial Risk
Not Medically Necessary Uses
Uses listed as Not Medically Necessary in the policy will not be approved. Confirm the requested drug and indication match the Medical Necessity sections; agents or indications listed under Not Medically Necessary are excluded from coverage.
Examples: products and indications listed in the Not Medically Necessary section (e.g., certain brands, formulations, or uses not in the Medical Necessity listings) will be denied.
If a non-covered indication is requested, consider non-formulary exception process with supporting clinical rationale.
Prior Authorization
Prerequisite Background Therapy
Prior authorization approvals commonly require documentation of prerequisite background therapy (statins, ezetimibe, fibrates, or other agents) and failure/intolerance to generics where specified. For some agents (e.g., statins, fibrates, omega‑3), trials of specified generics are required before brand products are approved.
HMG-CoA inhibitors: trial and failure or intolerance to TWO generic statins is required for brand statins.
Lovaza/Lovaza alternatives: trial and failure of generic omega‑3 acid ethyl esters or fibrates as specified in the criteria.
Prior Authorization
Maximally Tolerated Statin Required
Most authorizations require use of a maximally tolerated statin when indicated. If the member cannot tolerate a maximally tolerated statin, provide detailed documentation of intolerance and prior statin trials.
Maximally tolerated statin should be documented (dose, duration, adverse effects) when required by the drug-specific criteria.
Policy updates removed re-authorization requirement to continue using a maximum tolerated statin for several agents, but initial documentation of attempts is still required where specified.
Prior Authorization
Trial Exclusions May Affect Coverage
Clinical trial exclusion criteria and study populations may influence coverage expectations. Where pivotal trials excluded patients on specific background therapies (e.g., PCSK9 inhibitor use during inclisiran trials), document why the current patient differs or provide rationale for use despite exclusions.
If the patient was excluded from pivotal trial populations, include supportive rationale, alternative evidence, or specialty society guidance to justify therapy.
Examples: ORION trials excluded individuals taking PCSK9 inhibitors — explain current PCSK9 inhibitor status and LDL‑C goals.
Denial Risk
Denial Risk if Prior-Auth or Step-Therapy Not Met
Failure to meet prior authorization or step-therapy requirements is a frequent basis for denial. Providers should verify member benefit limits and submit complete documentation (see documentation callouts) to reduce denial risk.
Denials commonly occur when required prior trials, age criteria, or documentation (baseline LDL‑C, prior statin dosing/duration) are missing.
Before submission, confirm the member's benefit plan limits and any plan-specific exclusions.
Note
Benefit Plan Limits
Coverage is subject to member benefit plan limits. Providers and members should confirm plan-specific caps, age limits, and prior authorization durations; some non‑formulary exceptions may be approved up to 12 months per the policy updates.
Non-formulary exception review authorizations may be approved for up to 12 months.
Check benefit booklet or customer service for plan restrictions; this policy does not apply to Medicare Advantage.
Documentation Required
Required Medical Record Documentation
Medical records submitted for prior authorization must document that all medical necessity criteria are met. Include office visit notes with diagnosis, relevant history, physical exam, lipid panels (baseline and recent LDL‑C), and complete medication history including dates, doses, and responses.
Required: office visit notes, lipid panel results (baseline and most recent LDL‑C), prior medication trials with dates/doses, and documentation of statin intolerance if claimed.
For HeFH/HoFH, include diagnostic confirmation (genetic testing results or Simon Broome / Dutch Lipid Network score) when required.
Additional documentation commonly required with prior authorization requests includes baseline LDL‑C values, documentation of maximally tolerated statin use, trials of prior biologic or generic agents, and other drug-specific supporting records (e.g., pregnancy testing considerations for Evkeeza).
Baseline and recent LDL‑C values showing the need for intensification of therapy.
Document trials of prior biologic/generic agents (e.g., prior Repatha or Praluent trials where policy requires).
For Evkeeza, document age (policy updated to 5 years and older), HoFH diagnosis, prior LDL‑lowering therapies tried, and pregnancy testing/contraceptive counseling when applicable.
Evkeeza (evinacumab-dgnb) requests require documentation aligned with updated criteria: age (5 years and older for HoFH), diagnosis details, prior LDL‑lowering therapies tried, and background therapy. Include pregnancy testing/contraception counseling documentation for individuals who may become pregnant.
Evkeeza age requirement updated to 5 years and older (2024 update).
Document HoFH diagnosis and prior trials (Repatha prior trial required per updated step therapy).
Include pregnancy testing/contraception counseling due to embryo‑fetal toxicity warnings in the prescribing information.
Note
Prescribing Information and Non-Formulary Exception
Prescribers must follow the product's FDA dosing and administration prescribing information. For non-formulary requests, submit a non-formulary exception with supporting clinical rationale and documentation; exception approvals may be granted up to 12 months.
Medications are subject to FDA dosing/administration in the policy.
Non-formulary exception reviews may authorize coverage up to 12 months; include full clinical justification and required documentation.
Prior Authorization
Required Prior Biologic or Generic Trials
Prior biologic or specific generic trial evidence is required where noted in individual drug criteria. Document trials and outcomes of prior agents (e.g., prior Repatha or Praluent trials, trials of two generic statins for brand statin approval).
Examples: Repatha or Praluent trial required prior to Leqvio in certain indications; brand statins require failure/intolerance to two generics.
Include dates, doses, reason for discontinuation, and objective response (LDL‑C values) for each prior agent tried.
Prior Authorization
Background Therapy Requirement (Suggested)
Suggested background therapy expectations (where the policy references them) include continuation of guideline-directed medical therapy and maximally tolerated statin use, with additional agents (ezetimibe, fibrates, omega‑3s) as clinically indicated prior to or concurrent with specialty agents.
Where specified, document current guideline-directed medical therapy (GDMT) and the patient's response to that therapy.
Some agents allow approval without ongoing high‑intensity statin at re-authorization per 2024–2025 updates, but initial trials or intolerance must still be documented.
Step Therapy
Step Therapy Requirements Were Updated (Evkeeza and Juxtapid)
Step therapy requirements were updated in 2024–2025. Notably, Evkeeza and Juxtapid step requirements were revised to require prior trial of Repatha only (no longer require both Praluent and Repatha). Verify and document the specific prior agents tried per the current policy version.
Document trial of Repatha when seeking Evkeeza or Juxtapid per updated step therapy.
Confirm age and diagnostic criteria have been met for pediatric indications where applicable (Praluent and Repatha pediatric age updates).
Presence of tendon xanthomas in patient or first/second-degree relative supports definite FH
Genetic confirmationDNA-based evidence of LDLR, familial defective APOB, or PCSK9 mutation meets criteria
Possible (or Probable) Familial Hypercholesterolemia
Probable/Possible FH numeric thresholdsTotal cholesterol >260 mg/dL or LDL‑C >155 mg/dL in child; total cholesterol >290 mg/dL or LDL‑C ≥190 mg/dL in adult
Family history componentPlus family history of premature MI (relative age thresholds) or family history of raised cholesterol fulfills probable/possible FH
Use in diagnosisCombined numeric thresholds and family history classify as possible/probable FH per Simon Broome/Dutch criteria
Familial Hypercholesterolemia (FH) overview
OverviewFH is due to genetic defects causing severe LDL‑C elevation; diagnostic criteria include tendon xanthomas, family history, elevated LDL‑C thresholds, and scoring systems such as Dutch Lipid Network
Clinical consequenceLeads to premature atherosclerotic cardiovascular disease if untreated
Management implicationStatins are primary therapy; non‑statin LDL‑lowering agents considered when thresholds persist or intolerance exists
PCSK9 inhibitors
DefinitionMonoclonal antibodies (e.g., alirocumab, evolocumab) that inhibit PCSK9, increasing LDL receptor availability and lowering LDL‑C
ExamplesAlirocumab (Praluent) and evolocumab (Repatha)
Clinical roleUsed as add‑on to maximally tolerated statin therapy or when statin intolerance prevents adequate LDL‑C lowering
Inclisiran (Leqvio) definition
Agent class and mechanismInclisiran (Leqvio) is a small interfering RNA (siRNA) that inhibits PCSK9 mRNA, reducing PCSK9 protein and lowering LDL‑C
Dosing summaryAdminister 284 mg SC initially, at 3 months, then every 6 months thereafter
Trial contextStudied as add‑on to maximally tolerated statin therapy; trials excluded patients on PCSK9 inhibitors
HeFH definition
DefinitionHeterozygous familial hypercholesterolemia (HeFH): diagnosed by genotyping or clinical criteria (Simon Broome or WHO/Dutch Lipid Network) as used in trials
Numeric criterionOften defined with untreated LDL‑C ≥190 mg/dL or genetic confirmation
Clinical relevanceHeFH patients were included in trials evaluating PCSK9 inhibitors and inclisiran for additional LDL‑C reduction
HoFH definition
DefinitionHomozygous familial hypercholesterolemia (HoFH): two mutant alleles (LDLR/APOB/PCSK9/LDLRAP1) or very high LDL-C consistent with HoFH
LDL thresholdsUntreated LDL‑C >400 mg/dL or treated LDL‑C ≥300 mg/dL commonly used to define HoFH in policy criteria
Treatment contextHoFH patients were the population in ELIPSE‑HoFH trials evaluating evinacumab (Evkeeza)
Tryngolza (olezarsen) definition
Drug class and mechanismTryngolza (olezarsen) is an antisense oligonucleotide‑GalNAc3 conjugate that binds apoC‑III mRNA leading to reduced apoC‑III protein and lower serum triglycerides
IndicationFDA approved as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS)
Dosing (trialed)Evaluated at 80 mg SC every 4 weeks in BALANCE trial; policy limits dose to 80 mg once monthly
Evkeeza (evinacumab) definition
Drug and targetEvkeeza (evinacumab) is a monoclonal antibody targeting ANGPTL3 that reduces LDL‑C and other lipid parameters
Indication and evidenceShown to significantly reduce LDL‑C (~47% mean reduction at 24 weeks) in homozygous familial hypercholesterolemia (ELIPSE‑HoFH)
Safety considerationsWarnings include hypersensitivity reactions and potential embryo‑fetal toxicity; pregnancy testing and contraception advised
Diagnostic criteria for familial hypercholesterolemia simplified, LDL-C target changed from 100 mg/dL to 70 mg/dL, CK testing for myalgia removed, and specialty prescribing requirement eliminated.
04/01/2020interim_update
Policy renamed to 'Pharmacologic Treatment of High Cholesterol' and criteria added for Vascepa (icosapent ethyl), Nexletol (bempedoic acid), and Nexlizet; several formulations moved into the policy.
03/01/2022annual_review_coding
Added coverage criteria for Leqvio (inclisiran) and associated HCPCS code J3490 (later removed in 07/01/22 coding update); expanded primary hyperlipidemia indications.
07/01/2022coding_update
Added HCPCS code J1306 for inclisiran and removed HCPCS code J3490 from the policy coding list.
07/01/2024annual_review
Updated coverage criteria to include primary hyperlipidemia indications for Leqvio, Repatha, Praluent, Nexletol, and Nexlizet; Evkeeza age requirement lowered to 5 years and other age/step-therapy and diagnostic criteria updated.
03/01/2025annual_review_material_changeLatest
Removed re-authorization requirement to continue using a maximum tolerated statin across multiple agents; added coverage criteria for Tryngolza (olezarsen); HCPCS J3490 added back to report Tryngolza; clarified FDA dosing and non-formulary exception authorization up to 12 months.
05/01/2025interim_update
Interim review approved April 8, 2025: added coverage for Atorvaliq (atorvastatin oral suspension) for treatment of hyperlipidemia.