Repatha (evolocumab) is an injectable PCSK9 inhibitor that lowers LDL cholesterol by 50–60% on top of statin therapy. It is given as a subcutaneous injection every 2 weeks or once monthly, and has been proven to reduce heart attacks and strokes in high-risk patients (FOURIER trial).
Repatha (evolocumab) is a human monoclonal antibody manufactured by Amgen, FDA-approved in 2015. It belongs to the class of PCSK9 inhibitors — drugs that dramatically lower LDL ("bad") cholesterol by blocking a protein that would otherwise destroy LDL receptors in the liver.
How Does Repatha Work?
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein produced by the liver that binds to LDL receptors and tags them for destruction. Fewer LDL receptors means less LDL is cleared from the blood, so LDL levels rise.
Evolocumab is a monoclonal antibody that binds and inactivates PCSK9. With PCSK9 blocked:
- LDL receptors are recycled back to the liver cell surface instead of being destroyed
- More LDL is cleared from the blood with each pass through the liver
- LDL falls by 50–60% on top of statin therapy
Who Is Repatha For?
Repatha is FDA-approved for three main groups:
- Primary prevention — very high risk: Adults with clinical atherosclerotic cardiovascular disease (ASCVD) — prior heart attack, stroke, or peripheral artery disease — who need additional LDL lowering beyond maximally tolerated statins
- Familial Hypercholesterolemia (FH): Heterozygous or homozygous FH where LDL is severely elevated despite maximum statin + ezetimibe therapy
- Statin-intolerant patients with established ASCVD or FH who cannot tolerate adequate statin doses
🎯 LDL targets: For patients with established ASCVD, current guidelines recommend LDL <70 mg/dL (many experts recommend <55 mg/dL). PCSK9 inhibitors like Repatha help reach these aggressive targets when statins alone are insufficient.
FOURIER Trial — The Evidence
The landmark FOURIER trial (2017) enrolled 27,564 patients with ASCVD already on statin therapy and randomized them to evolocumab vs. placebo. Key results over ~2.2 years:
| Outcome | Reduction with Evolocumab |
|---|---|
| LDL reduction | 59% (from median 92 → 30 mg/dL) |
| Composite CV events (MI, stroke, CV death, revascularization) | 15% relative risk reduction |
| Heart attack | 27% reduction |
| Stroke | 21% reduction |
Importantly, the longer patients were treated, the greater the benefit — suggesting cumulative LDL burden reduction matters.
Dosing and Administration
- Every 2 weeks: 140 mg subcutaneous injection (autoinjector or prefilled syringe)
- Once monthly: 420 mg subcutaneous injection (3 consecutive 140 mg injections within 30 minutes, or single-use prefilled cartridge device)
- Inject into the abdomen, thigh, or upper arm — rotate sites
- Store in refrigerator; can be left at room temperature for up to 30 days
- Begin to see LDL lowering within 1–2 weeks; full effect by 4 weeks
Side Effects and Safety
Repatha is generally very well tolerated. The most common side effects are:
- Injection site reactions (redness, pain, bruising) — usually mild and transient
- Nasopharyngitis (common cold symptoms)
- Back pain, upper respiratory tract infection
PCSK9 inhibitors do not cause myopathy (muscle problems) or liver damage — the side effects associated with statins. They are safe to use in patients who are statin-intolerant due to muscle side effects.
💰 Insurance and Cost: Repatha typically requires prior authorization. Your provider will need to document that you have ASCVD or FH and that LDL is not at goal on maximum tolerated statin ± ezetimibe. Amgen offers a copay card (Repatha360) that can reduce out-of-pocket cost significantly for eligible patients.
Repatha vs. Other PCSK9 Inhibitors
| Drug | Manufacturer | Dosing | LDL Reduction |
|---|---|---|---|
| Repatha (evolocumab) | Amgen | 140 mg Q2W or 420 mg monthly | ~59% |
| Praluent (alirocumab) | Sanofi/Regeneron | 75–150 mg Q2W | ~46–60% |
| Leqvio (inclisiran) | Novartis | 284 mg Q6 months (siRNA) | ~50% |
Key Takeaways
- Repatha blocks PCSK9, allowing more LDL receptors to clear LDL from the blood
- Reduces LDL by ~59% on top of statin therapy
- Proven to reduce heart attacks and strokes in the FOURIER trial
- Indicated for ASCVD, familial hypercholesterolemia, or statin intolerance with high CV risk
- Injected every 2 weeks (140 mg) or monthly (420 mg); well-tolerated
- Requires prior authorization — your provider submits documentation of ASCVD/FH and failure of statin + ezetimibe
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