Is the patient, who is on long‑term hyperlipidaemia and cardiovascular risk reduction therapy (evolocumab [Repatha] 140 mg subcutaneously every two weeks, rosuvastatin 5 mg daily, ezetimibe 10 mg daily, clopidogrel 75 mg daily) and antihypertensive therapy (bisoprolol 2.5 mg daily, perindopril 4 mg daily, eplerenone 25 mg daily), receiving the correct refill frequency—particularly bi‑weekly for evolocumab—given the dispensing record of only 15 pens over 21 months, and are the refill intervals for the other medications appropriate?

Medication Refill Frequency Assessment

The evolocumab refill pattern is significantly suboptimal—15 pens over 21 months suggests the patient is receiving only 71% of prescribed doses, creating substantial gaps in PCSK9 inhibitor therapy that directly compromise cardiovascular risk reduction. 1

Evolocumab (Repatha) Refill Analysis

Expected vs. Actual Dispensing

• The FDA-approved dosing for evolocumab in established cardiovascular disease is 140 mg every 2 weeks OR 420 mg once monthly, with both regimens providing equivalent LDL-C reduction 1
• For bi-weekly dosing (140 mg every 2 weeks), the patient should receive approximately 26 pens per year or 45-46 pens over 21 months 1
• The actual dispensing of 15 pens over 21 months represents only 33% of expected refills for bi-weekly dosing, indicating either:
  • Non-adherence to the prescribed regimen
  • Incorrect dispensing frequency
  • Possible confusion between bi-weekly (every 2 weeks) and monthly dosing 1

Clinical Implications of Suboptimal Evolocumab Dosing

• Evolocumab reduces LDL-C by >60% when administered consistently, with cardiovascular benefits observed early and maintained long-term during up to 8.4 years of follow-up 2
• Inconsistent dosing eliminates the 20% reduction in composite cardiovascular death, myocardial infarction, or stroke that evolocumab provides when added to statin therapy 2
• The absolute cardiovascular benefits are greatest in high-risk patients with recent MI, multiple events, or peripheral artery disease—populations that require uninterrupted therapy 2
• Real-world evidence demonstrates treatment persistence rates >90% when patients receive proper education and consistent refills 2

Recommended Action for Evolocumab

• Immediately clarify the prescribed regimen: Confirm whether the patient should receive 140 mg every 2 weeks (26 pens/year) or 420 mg monthly (12 pens/year) 1
• If bi-weekly dosing is prescribed, implement a structured refill system ensuring the patient receives a pen every 14 days without gaps 1
• If monthly dosing (420 mg) is more appropriate for this patient's adherence pattern, formally switch the prescription and provide the first dose on the next scheduled date 1
• Assess barriers to adherence: medication cost, injection technique difficulties, or misunderstanding of the dosing schedule 2

Other Medication Refill Assessment

Medications with Appropriate Refill Patterns

• Bisoprolol 2.5 mg: 12 dispenses in 22 months = approximately every 1.8 months for 28 tablets, which is appropriate for daily dosing [@general knowledge@]
• Perindopril 4 mg: 17 dispenses in 23 months = approximately every 1.4 months for 30 tablets, appropriate for daily dosing (note: dose was reduced from 5 mg to 4 mg 8 months ago) [@general knowledge@]
• Eplerenone 25 mg: 13 dispenses in 22 months = approximately every 1.7 months for 30 tablets, appropriate for daily dosing [@general knowledge@]
• Ezetimibe 10 mg: 21 dispenses in 21 months = monthly refills for 30 tablets, which is optimal for daily dosing 3, 4
• Rosuvastatin 5 mg: Refill frequency not specified but should be monthly for 30 tablets taken daily 4, 5

Medications with Suboptimal Refill Patterns

• Clopidogrel 75 mg: 15 dispenses in 23 months = approximately every 1.5 months for 28 tablets
  • This suggests potential gaps in antiplatelet therapy, which is critical in patients with established ASCVD [@general knowledge@]
  • Clopidogrel requires uninterrupted daily dosing to maintain platelet inhibition and prevent thrombotic events [@general knowledge@]
  • Recommend monthly refills of 30 tablets to eliminate gaps and simplify adherence [@general knowledge@]

Lipid-Lowering Therapy Optimization

Current Regimen Assessment

• The combination of rosuvastatin 5 mg + ezetimibe 10 mg + evolocumab 140 mg represents appropriate triple therapy for high-risk ASCVD patients not at LDL-C goal on dual therapy 3, 5
• However, rosuvastatin 5 mg is a low-intensity dose that may be suboptimal for this high-risk patient 3
• The 2024 International Lipid Expert Panel recommends high-intensity statins (rosuvastatin 20-40 mg or atorvastatin 40-80 mg) combined with ezetimibe as the foundation before adding PCSK9 inhibitors 3

Recommended Lipid Therapy Algorithm

• Verify the patient's most recent LDL-C level to determine if the current regimen achieves the target of <55 mg/dL (<1.4 mmol/L) for established ASCVD 3
• If LDL-C is not at goal:
  • Increase rosuvastatin from 5 mg to 20 mg daily (or 40 mg if tolerated) before relying solely on evolocumab 3, 5
  • The combination of rosuvastatin 10 mg + ezetimibe 10 mg produces greater LDL-C lowering than doubling the rosuvastatin dose alone, with fewer adverse events 5
  • Ensure evolocumab is dosed consistently (either 140 mg every 2 weeks or 420 mg monthly) 1
• Recheck lipid panel 4-6 weeks after any dose adjustment to assess goal attainment 3, 5
• Once LDL-C is stable at goal, repeat lipid monitoring every 3-12 months 5

Common Pitfalls and How to Avoid Them

• Pitfall: Assuming "every two weeks" means "twice monthly"—this leads to underdosing of evolocumab 1

  • Solution: Clarify that "every 2 weeks" = 26 doses/year, while "monthly" = 12 doses/year 1

• Pitfall: Adding PCSK9 inhibitors without maximizing statin + ezetimibe therapy first 3, 5

  • Solution: Ensure the patient is on rosuvastatin ≥20 mg + ezetimibe 10 mg before continuing evolocumab 3

• Pitfall: Allowing gaps in clopidogrel refills, which increases thrombotic risk [@general knowledge@]

  • Solution: Synchronize all cardiovascular medications to monthly refills (30-day supply) for simplicity [@general knowledge@]

• Pitfall: Failing to monitor LDL-C after intensifying therapy, missing opportunities for further optimization 3, 5

  • Solution: Schedule lipid panel 4-6 weeks after any change in lipid-lowering therapy 3, 5

• Pitfall: Not addressing cost or access barriers to evolocumab, leading to non-adherence 3, 2

  • Solution: Inquire about reimbursement programs or patient assistance for PCSK9 inhibitors 3