Inclisiran (Leqvio®) position statement

This webpage was originally published on 2 December 2021. It was previously updated in August 2022 and most recently in March 2026. 

For any feedback, please contact policy@rcgp.org.uk

Background

Inclisiran (Leqvio®) is a novel medication designed to reduce the level of LDL-cholesterol in the blood and works by inhibiting the production of PCSK9 in the liver. It differs from other PCSK9 inhibitors in that it has an intracellular method of action preventing the translation of the PCSK9 protein, whereas others (e.g. alirocumab and evolocumab) bind to and inhibit the protein directly. In England, NICE has determined it is cost effective for secondary prevention) in certain patients. 

These are patients who have a history of cardiovascular events and a persistent LDL-C level of 2.6mmol/l or more, despite maximum tolerated lipid lowering therapies.1 In Scotland, the threshold is higher, requiring an LDL-C of 3.5mmol/l before prescribing in this group and is only approved for use in secondary care. In England, NICE suggests the drug may be administered in a primary care setting,1 subject to local commissioning and implementation arrangements. The SPIRIT implementation research project, sponsored by Novartis, was conducted in Greater Manchester. 

This assessed the feasibility of delivering inclisiran within a primary care setting, aiming to recruit 900 patients across approximately 20 practices. Interim and process-evaluation results of this trial have now been published, 2 however, definitive clinical outcome data has not been reported.

RCGP position

Cardiovascular disease prevention is a high priority for GPs, and integral to the College’s Clinical Policy priority – Preventive Medicine. Whilst the RCGP fully support innovation and promoting population health approaches to care, we have ongoing questions regarding this novel medication. Our priority is to ensure the best possible care for patients.

The following are some of our concerns:

  • The lack of long-term data on cardiovascular outcomes – findings from dedicated cardiovascular studies are still awaited 
  • The lack of long-term safety data and as yet potential unknown long term side effects and interactions of the medication, noting that longer-term extension studies have not identified new safety signals, but real-world and outcomes-based safety data are still emerging 
  • The additional capacity and resources which are required in primary care to deliver this drug at a time of unprecedented demand and shortages in workforce

RCGP encourages practices to continue to treat patients with high cholesterol, following lipid guidelines focussing on all available options starting with lifestyle changes and statins. We encourage escalating patients to high intensity statins and ezetimibe where appropriate. If considering injectable therapies, consider all options. Be aware that if you initiate inclisiran in primary care or continue to prescribe the medication following initiation elsewhere as the decision maker, you take full responsibility for the prescribing.

If you do decide to prescribe it before the long-term outcome and safety data is realised, please ensure you:

  • Undertake shared decision-making with your patients, ensuring a full and detailed informed consent is taken, documenting the lack of long-term evidence and unknown long term safety profile of this new and novel medication
  • Encourage your patients to report all side effects to you, however minor, ensuring you fill in a MHRA “yellow card” when they are reported to you and 
  • Report any potential drug interactions or concerns of your own at the earliest opportunity

This approach will enable any as yet unknown issues to be identified early and help inform how the medication can be used in the future, alongside the trial data that are awaited.

Additional resources

The BMA has provided updated advice on prescribing inclisiran (Leqvio®) in general practice

Next steps

The RCGP and BMA will continue to monitor the situation and communicate an update to our members once we have further details of the long-term trial data.

References

  1. NICE (2021) Technology appraisal guidance - Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia
  2. Wilson, P., Elvey, R., Mathieson, A., Bower, P., Gibson, M., Vell, T. and Dixon, S. (2025). Evaluating the implementation of inclisiran in primary care: process evaluation interim findings from interviews with key stakeholders. BMJ Open,15(2), pp.e083441–e083441.