Transitioning from Leqvio to Repatha
You can simply discontinue Leqvio (inclisiran) and immediately start Repatha (evolocumab) without any washout period, as both are PCSK9 inhibitors that work through different mechanisms and do not require dose tapering or overlap.
Practical Transition Protocol
Timing and Administration
- Stop inclisiran at any point in its dosing cycle (no need to wait for the next scheduled dose)
- Start evolocumab immediately using standard dosing:
- 140 mg subcutaneously every 2 weeks, OR
- 420 mg subcutaneously once monthly 1
- No washout period is required between agents
- No dose adjustment or titration needed
Why This Transition Works
Both medications target PCSK9 but through different mechanisms 1:
- Inclisiran is a small interfering RNA (siRNA) that suppresses hepatic PCSK9 synthesis
- Evolocumab is a monoclonal antibody that binds circulating PCSK9
Because they don't interact pharmacologically and inclisiran doesn't require tapering, the switch is straightforward. Real-world data confirms that patients transitioning between these agents maintain stable LDL-C control 2.
Clinical Considerations for the Switch
When to Consider This Transition
The 2022 ACC Expert Consensus specifically states that PCSK9 monoclonal antibodies (like Repatha) are preferred as the initial PCSK9 inhibitor of choice due to proven cardiovascular outcomes benefits in the FOURIER trial 1. Inclisiran may be considered primarily for:
- Patients with demonstrated poor adherence to PCSK9 mAbs
- Those unable to self-inject
- Patients experiencing adverse effects from both available PCSK9 mAbs
Expected LDL-C Response
- Evolocumab reduces LDL-C by approximately 58-64% when added to statin therapy 1
- Real-world data shows that switching from evolocumab to inclisiran generally maintains LDL-C levels, suggesting the reverse transition should be equally effective 2
- Recent meta-analysis found no significant differences in Lp(a) reduction between evolocumab, alirocumab, and inclisiran 3
Monitoring After Transition
- Check LDL-C at 4-8 weeks after starting evolocumab to confirm adequate response
- Monitor more closely in patients with heterozygous familial hypercholesterolemia (HeFH), as they may be more likely to exceed LDL-C targets during transitions 2
- Target: LDL-C <70 mg/dL for secondary prevention in ASCVD patients 1
Important Caveats
Patient-Specific Factors
Do not combine inclisiran with evolocumab - there is no evidence or mechanistic plausibility for additional efficacy, and if inclisiran is used, it should be in place of a PCSK9 mAb 1. This is a critical point: these agents replace each other, they don't augment each other.
Rare Non-Responders
While uncommon, some patients may not respond adequately to PCSK9 inhibitors due to:
- Elevated lipoprotein(a)
- Familial hypercholesterolemia variants
- Unknown biological factors 4
If inadequate response occurs after the transition, consider referral to a lipid specialist and evaluation for alternative therapies including bempedoic acid, ezetimibe optimization, or LDL apheresis in severe cases 1.
Dosing Flexibility
Evolocumab offers two dosing regimens with equivalent efficacy. The every-2-week regimen (140 mg) was used by 86% of patients in the FOURIER trial 5. Choose based on patient preference, though the biweekly option may improve adherence for some patients.
Storage Requirements
Unlike inclisiran's twice-yearly dosing advantage, evolocumab requires refrigeration at 2-8°C and more frequent administration 6. Ensure patients have appropriate storage and are comfortable with the increased injection frequency before transitioning.