This is general health information only and is not a substitute for advice from your GP or healthcare professional.
1. What are evolocumab and inclisiran?
Evolocumab and inclisiran are medicines that target PCSK9, a protein involved in regulating LDL cholesterol. Both can substantially reduce LDL-C, but they work in different ways. Evolocumab is a monoclonal antibody that directly blocks circulating PCSK9, while inclisiran is a small interfering RNA (siRNA) medicine that reduces the liver’s production of PCSK9.
2. How does evolocumab work?
Evolocumab binds to and inhibits PCSK9 in the bloodstream. This prevents PCSK9 from causing LDL receptors on liver cells to be broken down. More LDL receptors remain available to remove LDL cholesterol from the blood, resulting in a substantial reduction in LDL-C.
3. How does inclisiran work?
Inclisiran enters liver cells and uses RNA interference to reduce the production of PCSK9. With less PCSK9 being produced, more LDL receptors remain available on liver cells to remove LDL cholesterol from the bloodstream. Its long duration of action allows it to be administered infrequently.
4. How are evolocumab and inclisiran administered?
Evolocumab is usually given as a subcutaneous injection every two weeks or, depending on the regimen, once monthly. Inclisiran is administered as a subcutaneous injection initially, again at three months, and then every six months. The infrequent dosing of inclisiran may be convenient for people who have difficulty remembering regular medication.
5. Which reduces LDL cholesterol more effectively?
Both medicines can produce substantial LDL-C reductions, generally around 50% or more when appropriately used. Evolocumab has extensive randomised clinical trial evidence demonstrating both LDL-C reduction and cardiovascular event reduction. Inclisiran also produces sustained LDL-C lowering, but direct head-to-head evidence comparing the two medicines is limited.
6. Do both medicines reduce heart attacks and strokes?
Evolocumab has strong clinical outcome evidence demonstrating a reduction in major cardiovascular events, including myocardial infarction and stroke, particularly in people with established atherosclerotic cardiovascular disease. Inclisiran has demonstrated substantial and sustained LDL-C reduction, but definitive evidence that it reduces cardiovascular events is still being established in dedicated outcome trials.
7. Which one is better for someone who has difficulty with medication adherence?
Inclisiran may be particularly attractive when adherence to frequent medication is a concern because, after the initial and three-month doses, it is administered only twice a year. Evolocumab requires more frequent injections but has the advantage of extensive cardiovascular outcome evidence.
8. Can evolocumab or inclisiran be used with statins?
Yes. Both can be used alongside statins and other lipid-lowering medicines such as ezetimibe. They are generally considered when LDL-C remains above the recommended target despite maximally tolerated standard therapy, or when standard treatment cannot be tolerated.
9. What are the side effects of evolocumab and inclisiran?
Both medicines are generally well tolerated. Evolocumab can cause injection-site reactions, muscle aches, headache, and flu-like symptoms. Inclisiran most commonly causes injection-site reactions, which are usually mild and temporary. Serious allergic reactions are uncommon with both treatments.
10. Which is better: evolocumab or inclisiran?
There is no single best choice for everyone. Evolocumab currently has the stronger established evidence for reducing cardiovascular events, while inclisiran offers the convenience of twice-yearly maintenance dosing and sustained LDL-C reduction. The choice should consider the patient’s cardiovascular risk, LDL-C target, adherence, access, cost, injection preferences, and the strength of clinical outcome evidence required.