What are the implications of the BMJ publication on prescribing Repatha (evolocumab)?

Implications of the BMJ Publication on Prescribing Repatha (Evolocumab)

The BMJ publication on Repatha (evolocumab) suggests a more selective approach to prescribing this medication, recommending it primarily for patients with very high cardiovascular risk who have not achieved target LDL-C levels despite maximally tolerated statin therapy and ezetimibe.

Key Findings from the BMJ Publication

The BMJ publication provides risk-stratified recommendations for PCSK9 inhibitors like Repatha, emphasizing:

• A focus on absolute cardiovascular risk reduction rather than simply achieving LDL-C targets
• More selective use of PCSK9 inhibitors compared to some other guidelines
• Consideration of patient burden (including injection requirements and cost)
• Prioritization of adding ezetimibe before considering PCSK9 inhibitors 1

Clinical Efficacy and Safety

Evolocumab has demonstrated significant efficacy in reducing cardiovascular events:

• The FOURIER trial showed evolocumab reduced the primary endpoint (CV death, MI, stroke, revascularization, or hospitalization for unstable angina) with a hazard ratio of 0.85 (95% CI: 0.79-0.92) 1
• Evolocumab reduces LDL-C by 50-65% when added to statins 2
• The medication is generally well-tolerated with no significant differences in serious adverse events compared to placebo 2
• No evidence of increase in cognitive adverse effects was observed in the EBBINGHAUS study 1

Current Guideline Recommendations

The American College of Cardiology (ACC) recommends Repatha for:

• Adults with established cardiovascular disease to reduce major adverse cardiovascular events
• Patients with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)
• Adults and pediatric patients with homozygous familial hypercholesterolemia (HoFH) 1, 2

The European Society of Cardiology (ESC) considers Repatha in:

• Very high-risk patients not achieving LDL-C goals despite maximally tolerated statin therapy and ezetimibe 1, 2

Risk-Stratified Approach to Prescribing

Based on the BMJ publication and other guidelines, a risk-stratified approach to prescribing Repatha is recommended:

Highest Priority Patients (Strongest Recommendation)

• Patients with established ASCVD and LDL-C ≥70 mg/dL despite maximally tolerated statin plus ezetimibe
• Patients with familial hypercholesterolemia (particularly homozygous FH) not at goal with statins and ezetimibe
• Patients with multiple high-risk features (recent ACS, multiple prior MIs or strokes, polyvascular disease)

Secondary Priority Patients

• Statin-intolerant patients with high cardiovascular risk who cannot achieve adequate LDL-C reduction with other therapies
• Patients with diabetes and established ASCVD not at goal with statins and ezetimibe

Practical Prescribing Considerations

When prescribing Repatha:

• Dosage: 140 mg subcutaneously every 2 weeks or 420 mg once monthly 2
• For HoFH patients on apheresis: 420 mg every 2 weeks to coincide with apheresis schedule 2
• Administration: Subcutaneously in the abdomen, thigh, or upper arm 2
• Monitoring: LDL-C can be measured as early as 4 weeks after initiation 2

Barriers and Challenges

Important considerations when prescribing Repatha include:

• Prior authorization processes may be burdensome 1, 2
• High cost may restrict use despite excellent efficacy 2
• Patient acceptance of injectable therapy
• Need for long-term adherence

Conclusion

The BMJ publication reinforces a more selective approach to prescribing Repatha, focusing on patients with the highest cardiovascular risk and those who have not achieved target LDL-C levels despite maximally tolerated statin therapy and ezetimibe. This approach balances the significant clinical benefits of Repatha with considerations of cost, patient burden, and healthcare resource allocation.