Is Leqvio (Inclisiran) 284 mg subcutaneous every 12 weeks for 2 weeks then every 6 months medically necessary for the treatment of atherosclerosis of the native coronary artery without angina?

Medical Necessity Assessment for Leqvio (Inclisiran) in This Case

Based on the most recent documented LDL-C of 80 mg/dL from October 27,2025, this patient does NOT currently meet the Aetna coverage criteria for Leqvio, and the treatment is therefore not medically necessary at this time without additional documentation.

Critical Coverage Gap Analysis

Section A Criteria Assessment (ASCVD Pathway)

The patient partially meets Section A requirements but fails on a critical threshold 1:

• ✓ Criterion A1 (ASCVD History): Patient clearly meets this with documented MI in 2009, PCI with stents to LAD, 50-60% stenosis in left circumflex artery, and current diagnosis of atherosclerotic coronary artery disease 2

• ✗ Criterion A2 (LDL-C Threshold): The documented LDL-C of 80 mg/dL from 10/27/2025 exceeds the required threshold of ≥70 mg/dL for Section A2a, technically meeting this criterion 1, 3

• ✓ Criterion A3 (Statin Duration): Patient is on Atorvastatin 80 mg daily (high-intensity statin), though the duration of therapy is not documented 2

• ✓ Criterion A4 (Concomitant Statin): Patient will continue Atorvastatin 2

However, the physician's note states that labs from 11/4/2025 show increased LDL levels, which would potentially raise the LDL-C above 80 mg/dL and strengthen the case for approval. Without these documented lab values, the case cannot be definitively approved 1, 3.

Section B Criteria Assessment (Severe Hypercholesterolemia Pathway)

The patient fails Section B requirements 1:

• ✗ Criterion B1: Current LDL-C of 80 mg/dL is below the required ≥100 mg/dL threshold
• ? Criterion B2: No documentation of untreated baseline LDL-C ≥190 mg/dL before any lipid-lowering therapy was initiated

Clinical Guideline Context

Current Treatment Standards

The 2024 ESC Guidelines establish that patients with chronic coronary syndrome at very high cardiovascular risk should achieve LDL-C <55 mg/dL (1.4 mmol/L) with ≥50% reduction from baseline 2. This patient's LDL-C of 80 mg/dL is above this therapeutic target, supporting the clinical rationale for additional lipid-lowering therapy beyond statin monotherapy 2, 3.

The American College of Cardiology 2022 Expert Consensus supports inclisiran as an adjunct to maximally tolerated statin therapy for patients with clinical ASCVD requiring additional LDL-C lowering 1, 3. The patient's complex cardiac history (LVEF 31%, recurrent ischemia, ventricular tachycardia) places him at very high risk for recurrent cardiovascular events 2.

Evidence for Inclisiran Efficacy

• ORION-10 and ORION-11 trials demonstrated that inclisiran reduces LDL-C by approximately 50% (mean placebo-corrected reduction of 50.7% at day 510) when added to statin therapy 2, 1
• The VICTORION-INITIATE trial (2024) showed that an "inclisiran first" strategy achieved 60% LDL-C reduction vs 7% with usual care, with 81.8% of patients reaching LDL-C <70 mg/dL 4
• Inclisiran has demonstrated a favorable safety profile similar to placebo, with injection site reactions being the most common adverse event (5.0% vs 0.7%) 1, 5

Critical Documentation Deficiencies

Missing Information That Prevents Approval

1. November 4,2025 laboratory results: The physician states LDL and HDL increased on this date, but these values are not documented. If the LDL-C is ≥100 mg/dL on 11/4/2025, the patient would meet Section B1 criteria 1

2. Duration of Atorvastatin therapy: Coverage requires ≥3 months of high-intensity statin treatment. The start date is not documented 2, 1

3. Baseline untreated LDL-C: For Section B2, documentation of LDL-C ≥190 mg/dL before any lipid-lowering therapy would support approval 1

4. Reason for Repatha discontinuation: Understanding why the patient stopped PCSK9 monoclonal antibody therapy is relevant, as inclisiran is recommended as an alternative when PCSK9 antibodies cannot be used 2, 1

Recommendation for Case Resolution

To establish medical necessity, the following actions are required:

1. Obtain and document the November 4,2025 laboratory results showing the increased LDL-C level. If LDL-C ≥100 mg/dL, this would satisfy Section B1 1

2. Document the start date of Atorvastatin 80 mg to confirm ≥3 months of high-intensity statin therapy 2, 1

3. Obtain historical lipid panels to identify if the patient ever had untreated LDL-C ≥190 mg/dL, which would satisfy Section B2 1

4. Document the reason for Repatha discontinuation (intolerance, side effects, access issues) to support inclisiran as an alternative PCSK9 modulator 2, 1

Clinical Appropriateness Despite Coverage Gap

From a purely clinical standpoint, inclisiran therapy is appropriate and evidence-based for this patient 2, 4, 3:

• The patient has extensive ASCVD with severely reduced LVEF (31%), prior MI, coronary stenosis, and ventricular arrhythmias, placing him at extreme cardiovascular risk 2
• Current LDL-C of 80 mg/dL is significantly above the guideline-recommended target of <55 mg/dL for very high-risk patients 2
• The patient has demonstrated statin intolerance (rosuvastatin allergy) and discontinued prior PCSK9 inhibitor therapy, making inclisiran's twice-yearly dosing particularly advantageous for adherence 1, 5, 6
• The 2024 International Lipid Expert Panel recommends PCSK9 modulators (including inclisiran) when LDL-C targets are not achieved with statin plus ezetimibe 2

Standard of Care Assessment

Inclisiran is considered standard of care and is FDA-approved for adults with clinical ASCVD who require additional LDL-C lowering as an adjunct to diet and maximally tolerated statin therapy 1, 5, 6. The treatment is not experimental or investigational—it received FDA approval in 2021 and is included in major society guidelines including the American College of Cardiology Expert Consensus Decision Pathway and European Society of Cardiology Guidelines 2, 1.

The dosing regimen (284 mg subcutaneously at baseline, 3 months, then every 6 months) is the FDA-approved and guideline-recommended schedule 1, 6.

Common Pitfalls to Avoid

• Do not confuse the dosing schedule: The prescription states "every 12 weeks x 2" which should be clarified as "at baseline and 3 months (90 days)" followed by every 6 months 1, 6
• Do not overlook the distinction between clinical appropriateness and coverage criteria: This patient clinically warrants inclisiran based on cardiovascular risk and LDL-C above target, but insurance criteria require specific LDL-C thresholds with documentation 2, 1, 3
• Recognize that the October 27 LDL-C of 80 mg/dL may be outdated if the November 4 labs show increased levels, making timely documentation critical 4