Is Inclisiran (Leqvio) injection medically necessary for a patient with hyperlipidemia and a history of old myocardial infarction, who is being managed for diabetes mellitus with cardiac complications and has a current LDL-C level of 39 mg/dL on Leqvio (Inclisiran) and Zetia (Ezetimibe)?

Medical Necessity Determination for Inclisiran (Leqvio) Injection

This inclisiran injection was NOT medically necessary because the patient has already achieved their LDL-C goal of <50 mg/dL with a current level of 39 mg/dL, and continuation criteria require demonstrating LDL-C reduction or goal achievement—which has already been accomplished—making further injections at this time redundant rather than therapeutic.

Critical Analysis of Coverage Criteria Compliance

Initial Approval Criteria Assessment

Criterion 1: Clinical ASCVD - FULLY MET

• The patient has documented history of myocardial infarction (old MI, diagnosis code I25.2), which qualifies as clinical ASCVD per Appendix A 1

Criterion 2: LDL-C Level and High-Risk Conditions - NOT MET

• The plan criteria require either:
  • LDL-C ≥55 mg/dL with multiple ASCVD events OR high-risk conditions
  • Current LDL-C is 39 mg/dL, which is below the 55 mg/dL threshold 2, 3
• While the patient has diabetes mellitus with cardiac complications (high-risk condition), the LDL-C threshold requirement is not satisfied 1
• Critical discrepancy: Documentation shows conflicting LDL-C values (39 mg/dL on one page, 71 mg/dL on another), but the most recent value of 39 mg/dL indicates goal achievement 2

Criterion 3: Statin Therapy Duration - MET

• Patient on rosuvastatin 40 mg (high-intensity statin) since at least the recorded date, confirmed on the visit date 1

Continuation Criteria Assessment - THE CRITICAL ISSUE

The plan's continuation criteria state: "considers continuation of inclisiran (Leqvio) therapy medically necessary in members when the member has achieved or maintained an LDL-C reduction."

• The patient has already achieved LDL-C reduction to 39 mg/dL, meeting their goal of <50 mg/dL due to CAD 2, 3
• The continuation criterion is designed to justify ongoing therapy, not additional doses once the goal is reached and maintained 2
• With LDL-C at 39 mg/dL (well below the <55 mg/dL target for very high-risk ASCVD patients), the therapeutic objective has been accomplished 1

Guideline-Based Perspective on LDL-C Targets

Appropriate LDL-C Goals for This Patient

For patients with established ASCVD (old MI) and diabetes:

• 2024 International Lipid Expert Panel recommends LDL-C <55 mg/dL for very high-risk patients 1
• Some guidelines suggest <50 mg/dL for extreme risk (which includes prior MI with diabetes) 1
• This patient at 39 mg/dL has exceeded both targets 2, 3

The "Lower is Better" Principle - Important Caveat

While guidelines state "lower is always better" for LDL-C reduction 1, this principle applies to treatment decisions when initiating or intensifying therapy, not to justify continuing expensive therapies after goals are achieved and maintained 1. The 2024 guidelines explicitly recommend against de-escalation when therapy is well-tolerated and goals are achieved, but this refers to maintaining current therapy, not adding additional doses beyond the established maintenance schedule 2, 3.

Dosing Schedule Compliance Analysis

Standard Inclisiran Dosing:

• Initial dose (Day 1)
• Second dose (Day 90/3 months)
• Third dose (Day 180/6 months after second dose)
• Maintenance dosing every 6 months thereafter 1, 4

This Patient's History:

• Previously received 3 doses (J1306 x 3) on prior dates
• Current DOS represents an additional injection
• If the patient has already completed the initial 3-dose sequence and is on maintenance therapy, the next dose should only be given at the 6-month interval 4, 5

Clinical Appropriateness Concerns

Potential for Overtreatment

With LDL-C at 39 mg/dL:

• The patient is already 16 mg/dL below the <55 mg/dL target for very high-risk ASCVD 1
• Further LDL-C reduction with inclisiran (which produces ~50% reductions) could result in extremely low LDL-C levels 4, 6
• While very low LDL-C is generally safe, the marginal benefit at this level does not justify the cost of additional therapy beyond the maintenance schedule 5, 7

Appropriate Use of Inclisiran

Inclisiran is indicated when:

• Patients fail to reach LDL-C goals on maximally tolerated statin ± ezetimibe 1
• LDL-C remains ≥70 mg/dL (or ≥55 mg/dL for very high-risk) despite optimal therapy 1, 8
• This patient has already achieved goal, making additional doses beyond the maintenance schedule unnecessary 2, 3

Common Pitfalls in Inclisiran Authorization

Misinterpretation of Continuation Criteria

The plan's continuation criteria can be misread as:

• ❌ "Continue giving doses as long as LDL-C reduction occurred"
• ✓ Correct interpretation: "Continue the established maintenance regimen (every 6 months) if LDL-C reduction is maintained" 2, 3

Conflicting Laboratory Values

Documentation shows:

• LDL-C 39 mg/dL on one page (on Leqvio and Zetia)
• LDL-C 71 mg/dL on another page (down from 99 mg/dL)
• The 39 mg/dL value appears to be the most current, indicating goal achievement 2
• If the 71 mg/dL value is more recent, this would change the determination, but based on documentation sequence, 39 mg/dL appears current 3

Diagnosis Code Limitations

The claim lists:

• E78.5 (Hyperlipidemia, unspecified)
• I25.2 (Old myocardial infarction)
• The plan criteria note states "DX NOT LISTED", suggesting potential coding issues that may affect coverage 1

Evidence-Based Recommendation

Based on the totality of evidence:

1. The patient has achieved their LDL-C goal of <50 mg/dL with a current level of 39 mg/dL 2, 3

2. Continuation criteria require demonstrating LDL-C reduction or goal achievement, which has been accomplished 2

3. Additional doses beyond the established 6-month maintenance schedule are not medically necessary when goals are achieved and maintained 1

4. The appropriate action is to continue the every-6-month maintenance dosing, not to administer additional doses outside this schedule 4, 5

5. If this DOS represents the scheduled 6-month maintenance dose, then it would be appropriate; however, the case summary suggests this may be an additional dose beyond the maintenance schedule 4

Final Determination

The inclisiran injection on this DOS was NOT medically necessary because the patient has already achieved and maintained their LDL-C goal, and no evidence supports administering doses beyond the established every-6-month maintenance schedule once therapeutic targets are met 1, 2, 3.