Cost and Safety of Novel, Nonstatin Therapies

Safety and Cost-Effectiveness of Nonstatin Lipid-Lowering Therapies in Patients With Post-Atherosclerotic Cardiovascular Disease (ASCVD)

Safety Profiles

• Nonstatin therapies in real-world settings have demonstrated generally favorable safety profiles:
  • Ezetimibe: Well-tolerated with minimal adverse effects
  • PCSK9 inhibitors: No major safety concerns in extended use, with injection site reactions being the most common adverse event
  • Bempedoic acid: Shows lower rates of muscle-related adverse events than statins
  • Inclisiran: Demonstrates good tolerability with primarily injection site reactions
  • Complex comorbidities: Patients with renal impairment, diabetes, or advanced age show comparable safety profiles with nonstatin therapies vs clinical trials, though they require more monitoring

LDL-C Target Levels and Clinical Practice

• Very high-risk post-ASCVD patients: Guidelines recommend LDL-C target levels of less than 55 mg/dL (1.4 mmol/L) with some suggesting less than 40 mg/dL for patients with recurrent events
• Real-world practice: Often diverges from guidelines due to:
  • Physician inertia regarding aggressive LDL-C level lowering
  • Concerns about polypharmacy in patients with complex cases
  • Limited access to newer therapies

Cost Considerations Affecting Adoption

• PCSK9 inhibitors: Despite proven efficacy, high costs limit their widespread use
  • Most cost-effective in very high-risk patients with LDL-C levels greater than 100 mg/dL despite maximally tolerated statins
  • Prior authorization requirements continue to create significant barriers
• Bempedoic acid and inclisiran: More recent market entries with:
  • Better cost-effectiveness ratios than early PCSK9 inhibitor pricing
  • Emerging data supporting use in statin-intolerant patients
  • Variable insurance coverage affecting patient access
• Specific settings: Academic medical centers show higher adoption rates of novel therapies compared with community practices
• Patient populations: Greatest cost-effectiveness demonstrated in post-myocardial infarction (MI) patients with LDL-C levels greater than 100 mg/dL despite maximally tolerated statins, patients with familial hypercholesterolemia, and those with documented statin intolerance