❤️ Heart Health
PCSK9 Inhibitors — Evolocumab and Alirocumab Complete Guide (2026)
PCSK9 inhibitors reduce LDL by 50–60% on top of statins. Who needs them, how they work, NHS availability, and cost. Updated January 2026.
Key Takeaways
- PCSK9 inhibitors reduce LDL by an additional 50–60% on top of maximum statin therapy
- Now available as a twice-yearly injection (inclisiran) — vastly improved adherence
- NICE approved for familial hypercholesterolaemia and very high cardiovascular risk
- Cost was the major barrier — now available NHS in primary and secondary care
- In FOURIER trial: evolocumab reduced cardiovascular events by 15% on top of statins
What Are PCSK9 Inhibitors?
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that degrades LDL receptors on liver cells — reducing the liver's ability to clear LDL from the bloodstream. PCSK9 inhibitors block this protein, increasing LDL receptor expression and dramatically lowering LDL cholesterol.
50–60%
Additional LDL reduction on top of maximum statin
15%
Cardiovascular event reduction on top of statin (FOURIER)
2×/year
Inclisiran injection frequency — best adherence
Available PCSK9 Inhibitors
| Drug (Brand) | Type | Frequency | LDL Reduction | NHS Available |
|---|---|---|---|---|
| Evolocumab (Repatha) | Monoclonal antibody | Monthly or fortnightly | 50–60% | Yes — FH + ASCVD |
| Alirocumab (Praluent) | Monoclonal antibody | Fortnightly or monthly | 45–60% | Yes — FH + ASCVD |
| Inclisiran (Leqvio) | siRNA (gene silencing) | Twice yearly (after loading) | 50–55% | Yes — 2022 NHS |
Inclisiran — The Game Changer
Inclisiran is fundamentally different from evolocumab and alirocumab — it uses siRNA (small interfering RNA) technology to silence the PCSK9 gene in liver cells, reducing PCSK9 protein production rather than blocking the protein itself. Two initial injections (day 1 and day 90), then once every 6 months. This dramatically improves adherence compared to monthly injections and has transformed real-world outcomes.
Who Qualifies on the NHS?
- Heterozygous familial hypercholesterolaemia (HeFH) — LDL above target despite maximum tolerated statin + ezetimibe
- Established ASCVD (post-MI, stroke, PAD) with LDL above 1.8 mmol/L despite maximum statin + ezetimibe
- Statin intolerance — documented inability to tolerate statins with persistent high LDL
- NICE criteria apply — referral typically via cardiologist or lipid clinic
✅ Key Clinical Evidence
FOURIER trial (evolocumab, n=27,564): 15% reduction in cardiovascular events. ODYSSEY OUTCOMES (alirocumab, n=18,924): 15% CVD reduction, 15% all-cause mortality reduction. ORION-10 (inclisiran): equivalent LDL reduction to monthly antibodies with twice-yearly dosing. All three drugs are safe and well-tolerated with minimal side effects.🔢 Free Tool
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How do I get PCSK9 inhibitors on the NHS?▼
Referral to a specialist lipid clinic, cardiologist, or cardiology service is required. Your GP will refer you if you have FH or ASCVD with LDL persistently above target despite maximum statin + ezetimibe. NICE TA394 (evolocumab) and TA393 (alirocumab) provide the access criteria. Inclisiran is commissioned separately through NHS England primary care networks.
Are PCSK9 inhibitors safe long-term?▼
Yes — 7+ years of evolocumab safety data from FOURIER extension studies shows no new safety signals. Side effects are minimal: injection site reactions (rare), and slightly increased new-onset diabetes risk (smaller than statins). There are no drug interactions as they are biological agents. Muscle symptoms do not occur as they have no CYP450 metabolism.
Can I take PCSK9 inhibitors without statins?▼
Yes — in statin-intolerant patients, PCSK9 inhibitors alone are very effective. In GAUSS-3 trial, evolocumab reduced LDL by 53% in statin-intolerant patients. This is now an NHS indication for documented statin intolerance. The combination of ezetimibe + PCSK9 inhibitor (without statin) is a recommended alternative for intolerant patients.
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⚕️ Medical Disclaimer: For informational purposes only. Always consult a qualified healthcare professional before starting or changing any medication or treatment.
JO
Consultant Cardiologist
All articles reviewed by qualified healthcare professionals following NHS, AHA, and WHO guidelines.