GP leaders warn over the rollout of cholesterol lowering inclisiran in primary care

The BMA and the Royal College of General Practitioners (RCGP) say they have “serious concerns” about the rollout of the new cholesterol lowering drug inclisiran in primary care in England.1

In September, the National Institute for Health and Care Excellence (NICE) recommended the treatment, calling it “a potential game changer in preventing thousands of people from dying prematurely from heart attacks and strokes.”23 The health and social care secretary Sajid Javid called it a “ground breaking” new drug. NHS England said that nurses will be able to administer inclisiran as an injection in GP surgeries across England.

Inclisiran is a novel treatment which uses RNA interference to boost the liver’s ability to remove low density lipoprotein (LDL) cholesterol from the blood. It is given by injection at zero, three, and six months and then twice a year for life.

In England it is recommended in patients who have a history of cardiovascular events and a persistent LDL level of 2.6 mmol/L or more despite maximum tolerated lipid lowering therapies. In Scotland the threshold for treatment is higher at 3.5 mmol/L and it is only approved for use in secondary care.

The Spirit research project is currently underway in Greater Manchester looking at the feasibility of delivering the drug within primary care but the results will not be available until next year.

In a joint statement the BMA and RCGP say they have discussed the proposed rollout of inclisiran in primary care with NHS England and NHS Improvement following concerns raised by their members and a BMJ editorial asking for approval to be reconsidered.4

The statement says the main concerns “centre on the fact that inclisiran is a black triangle drug being proactively rolled out directly to primary care.” In particular there is a lack of long term data on cardiovascular outcomes with relevant studies not available until 2026 and a lack of long term safety data and as yet potential unknown long term side effects and interactions of the drug.

It adds that there are also problems around capacity, the lack of clear resources to support the additional work required, and the impact that introducing new treatment plans will have on teams that are already stretched to the limits.

The Medicines and Healthcare Products Regulatory Agency assigns a black triangle symbol to any drug or vaccine that is a new active substance, has a new route of administration, or is used in a new patient population. The symbol appears next to the product in the British National Formulary, drug safety updates, and advertising material. While a drug has a black triangle status it is subject to additional monitoring with healthcare professionals asked to report all suspected adverse drug reactions through the Yellow Card scheme.

The BMA said that although they are supportive of new drug innovation they are concerned about where the long term responsibility lies when prescribing this drug and the lack of clarity about where doctors and patients can turn if there are concerns or problems. The joint statement says that while they wait for clarification on their concerns GP practices should continue to treat patients with high cholesterol following lipid guidelines. “If considering injectable therapies consider all options, being aware that if you initiate inclisiran in primary care, as the decision maker, you take full responsibility for the prescribing.”

The guidance says GPs should only prescribe the drug “if they feel comfortable.” If they do decide to prescribe inclisiran before the long term outcome and safety data are realised they should ensure the patient is involved in a shared decision with full and detailed informed consent including documenting the lack of long term evidence and unknown long term safety profile of the drug. They should also encourage patients to report all side effects to them, however minor, and ensure the GP fills in a MHRA Yellow Card.

In an editorial for The BMJ, Paula Byrne, a research fellow at RCSI University of Medical and Health Sciences in Ireland, and others questioned why NICE recommended inclisiran without any data on clinically meaningful cardiovascular outcomes when clinical outcomes and better safety data will be available within five years. “We do not know if inclisiran will improve cardiovascular outcomes for patients, we do not know how much it will cost, and we have insufficient data on safety given the relatively small number of patients in trials to date.”

The editorial concluded, “The drug may prove to be a ‘game changer,’ or it may not. Clinicians and their patients need to be aware of the limitations in the evidence. NICE should reconsider its decision until patient relevant outcomes are available, and these, and all cost data, should be released for independent analysis.”