What is an alternative to Praluent (alirocumab) for a patient with high cholesterol who requires continued management due to significant cardiovascular risk?

Alternative to Praluent (Alirocumab) for High Cholesterol Management

Evolocumab (Repatha) is the preferred alternative to alirocumab, offering equivalent LDL-C reduction (58-64%) and proven cardiovascular outcomes benefits with similar safety profiles. 1, 2

Primary Alternative: Evolocumab (Repatha)

Evolocumab represents the most direct alternative as it is the other FDA-approved PCSK9 monoclonal antibody with demonstrated cardiovascular outcomes benefits comparable to alirocumab. 1, 2

Dosing and Administration

• Standard dosing: 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly 1, 2
• For homozygous familial hypercholesterolemia: 420 mg monthly, with option to increase to 420 mg every 2 weeks if additional LDL-C reduction needed after 12 weeks 1, 2
• Administration sites include thigh, abdomen, or upper arm 1

Efficacy Data

• LDL-C reduction: 58-64% when added to maximally tolerated statin therapy, achieving median LDL-C levels as low as 30 mg/dL 1, 2, 3
• FOURIER trial outcomes: 15% relative risk reduction in composite endpoint (CV death, MI, stroke, revascularization, or hospitalization for unstable angina) over 2.2 years 1, 2
• Major adverse cardiovascular events: 20% reduction in CV death, MI, or stroke (7.4% to 5.9%, P<0.001) 1, 3

Secondary Alternative: Inclisiran

Inclisiran offers the advantage of twice-yearly dosing (day 1, day 90, then every 6 months), making it particularly suitable for patients with poor adherence to biweekly or monthly injections. 1

Key Considerations for Inclisiran

• LDL-C reduction: 49.9-52.3% reduction at day 510 in ORION-10 and ORION-11 trials 1
• Cardiovascular outcomes: Exploratory analysis showed cardiovascular events in 7.4-7.8% of inclisiran group vs 10.2-10.3% of placebo group, though definitive outcomes trials (ORION-4, VICTORION-2P) are ongoing until 2026-2027 1
• Use in place of, not in addition to, PCSK9 monoclonal antibodies - no evidence supports combining inclisiran with alirocumab or evolocumab 1

Third-Line Alternative: Ezetimibe

For patients unable to use injectable therapies or requiring cost-effective options, ezetimibe provides oral administration with proven cardiovascular benefits, though with more modest LDL-C reduction. 1

Ezetimibe Characteristics

• LDL-C reduction: Approximately 20% when added to statin therapy 1
• IMPROVE-IT trial: 6.4% relative benefit and 2% absolute reduction in major adverse cardiovascular events over 6 years when added to simvastatin 1
• Advantages: Oral administration, generic availability, significantly lower cost than PCSK9 inhibitors 1

Fourth-Line Alternative: Bempedoic Acid

Bempedoic acid may be considered when evidence-based agents are contraindicated or not tolerated, particularly in patients with documented statin intolerance who prefer oral therapy. 1

Bempedoic Acid Profile

• LDL-C reduction: Approximately 17% mean reduction 1
• Advantages: Oral administration, no skeletal muscle symptoms, useful for statin-intolerant patients 4
• Cautions: Use with caution in patients with history of gout or tendon rupture; associated with small increase in plasma uric acid 1, 4
• Limitation: No cardiovascular outcomes data currently available 1

Clinical Decision Algorithm

Step 1: Assess Patient-Specific Factors

• Injection tolerance: If patient accepts injections and has good adherence → evolocumab 1, 2
• Poor adherence to frequent injections: Consider inclisiran (twice-yearly dosing) 1
• Injection aversion or cost constraints: Consider ezetimibe first, then bempedoic acid 1

Step 2: Evaluate Cardiovascular Risk Status

• Very high-risk ASCVD patients (recent ACS, multiple vascular beds involved): Prioritize evolocumab for proven outcomes benefits 1, 2
• Moderate-risk patients or primary prevention: Ezetimibe may be sufficient and cost-effective 1

Step 3: Consider Statin Intolerance

• Complete statin intolerance: PCSK9 inhibitor (evolocumab or inclisiran) strongly preferred over ezetimibe alone 1
• Partial statin intolerance: Ezetimibe plus low-dose statin, with PCSK9 inhibitor if targets not met 1

Important Caveats

Safety Profiles

• PCSK9 inhibitors (evolocumab, alirocumab): No increase in skeletal muscle symptoms, no increased diabetes risk, no major drug interactions 4
• Injection site reactions: Mild-to-moderate reactions occur with PCSK9 monoclonal antibodies but rarely lead to discontinuation 1, 4
• Hypersensitivity: Only contraindication to evolocumab is prior hypersensitivity reaction 1, 2

Prior Authorization Considerations

• Documentation requirements: Established ASCVD, maximally tolerated statin therapy, current LDL-C above target despite optimal therapy 5
• Renewal criteria: Demonstrate LDL-C reduction of at least 40-50% from baseline and continued clinical benefit 5

Combination Therapy Approach

If additional LDL-C lowering needed beyond maximally tolerated statin plus ezetimibe, add evolocumab rather than switching from ezetimibe. 1 If still inadequate, bempedoic acid may be added to the regimen (statin + ezetimibe + PCSK9 inhibitor + bempedoic acid). 1