The National Institute for Health & Care Excellence (NICE) approved the use of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) Evolocumab & Alirocumab in primary hypercholesterolaemia and mixed dyslipidaemia against a clear set of criteria. Up until the licensing of PCSK9i, we had very limited options for managing LDL-C among high risk patients who were either intolerant to statins or despite statin (and Ezetimibe) therapy, fail to meet target LDL-C levels.
The NICE published technology appraisal guidance TA393 and 394 provided a new opportunity and hope for those patients. Our large teaching hospitals set up an Innovative Medicines Optimisation Clinic to assess, initiate and monitor patients suitable for PCSK9i and optimise their lipid therapy to enable achieving optimal cholesterol targets.
- Alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia (TA393)
- Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia (TA394)
- Familial hypercholesterolaemia: identification and management (CG71)
- Cardiovascular disease: risk assessment and reduction, including lipid modification (CG181)
Aims and objectives
The aim of this project was to deliver a centralised PCSK9i service to improve access to these innovative therapies and ensure that they are offered to the right candidates who would be supported to gain maximum benefit. The clinic adopted a person-centred approach to enable optimising lipid therapy and support medicines adherence to meet LDL-C targets.
- Optimise lipid management among patients with hypercholesterolaemia who are statin intolerant or despite statin therapy are not meeting NICE defined low LDL-C targets.
- Examine statin intolerance and work in a person-centred fashion to identify a statin based regimen which meets patient needs, where applicable.
- Assess and where suitable offer PCSK9i to people across Leeds who may be eligible in line with NICE guidance.
- For those unsuitable, provide specialist patient-centred input to optimise lipid lowering treatment and ensure onward referral to the most suitable service.
- For those suitable provide a high level of patient tailored support and education to promote adherence with treatment and optimisation of LDL-C levels.
- Tailor monitoring of treatment for people using PSCK9 inhibitors to ensure the medicine is still appropriate for the patient and resources are being used effectively.
- As part of the planning process produce the following:
- A service guideline and clinic pathway to enable the screening of all referred patients against the NICE technology appraisals (TA394 and TA393) criteria for initiating these expensive medicines (see attachment).
- Full guidance on statin intolerance and how to manage, to ensure that PCSK9i are started in appropriate patients.
- A full registry was put in place to collect data about all patients seen in clinic, their response to therapy and experience with PCSK9i
Reasons for implementing your project
Current audits show that many patients are not meeting lipid targets due to many reasons. A large proportion of those are labelled as “Statin Intolerant”, some continue to have high LDL-C despite statin and Ezetimibe therapy, and others are non-adherent. The guidance recommending Evolocumab & Alirocumab for specified high risk patients offers a good opportunity to better control LDL-C for many of those patients. The recommendations made in the NICE FH guideline (CG71) about identifying and managing patients with FH alongside the genetic testing and cascade family screening for FH starting across Yorkshire made it more important to establish a service which meets the needs of patient with hypercholesterolaemia (± FH).
Furthermore, the NHS is obliged to make NICE’s recommendations available and funded within 3 months (unless otherwise specified) of the guidance publication date.
The NICE TA published in summer 2016 estimated that in Leeds (CCGs) around 200 patients would qualify for these medicines. However, in light of the recommendations made by NICE in the familial hypercholesterolaemia: identification and management clinical guideline (CG71) in Nov 2017 the estimates became higher.
We chose a specialist multidisciplinary model to deliver the PCSK9i clinic because the nature of the condition requires cross-specialty input and these medicines should be started by specialists. The model ensures that patients are assessed by specialists in cardiology or lipidology and those initiated on PCSK9i meet NICE criteria. Those who do not meet criteria are supported by experts in medicines optimisation to achieve better lipid management with minimum negative impact on their quality of life. This approach maximises patient benefits and reduces medicines wastage. The support provided to patients and follow up calls are more likely to increase adherence and ensure that patients are fully optimised and monitored. The team ruled out the option of community care prescribing the medications because the cost of PCSK9i is reduced for secondary care and this saving is passed on to commissioners. It was agreed that Leeds Teaching Hospital Trust would supply these medicines long term.
How did you implement the project
A steering committee was established and included representation from cardiology, pharmacy, and lipidology. The two main settings for identifying patients who needed PCSK9i was the lipid clinic and cardiology, however, the lipid clinic did not have capacity to host this new service. Cardiology already had some experience with Evolocumab as part of a research study. This offered an experienced cardiology research nurse to support the service. The already established pharmacy-led multidisciplinary cardiology outpatient innovative medicines optimisation services were ideal to host this new service. Pharmacy offered a consultant pharmacist to lead the establishment of the service.
A joint clinical working agreement was seen to be the way forward and our team took swift action to secure access to PCSK9i through the establishment of the Pharmacy-Led Multidisciplinary Innovative Medicines Clinic. Commissioners were engaged early in the planning process. The plan was for the clinic to be led by a consultant pharmacist and supported by a cardiology nurse. Cardiology and the lipid clinic will also support the service. After the service was established an advanced pharmacist was recruited to support the bulk of the service.
The service runs two clinics per week and includes additional time for follow ups with phone calls, supply and monitoring.
All patients are referred to the centralised service (see attachment for details) . Referrals are discussed by the team running the clinic, and where needed the steering committee are contacted for further advice. Suitable patients are invited to attend the clinic, and offered the medicines as per guidelines. Appropriate blood tests are carried out at baseline. Patients who agree to try the medicine are provided with full education about the medicines and how to administer the injectable drug, how to dispose of it, and how to store it safely.
One dose is administered in clinic and a second is given to the patient to administer two weeks after. Patients are followed up by 2 phone calls to discuss experience and decide if they want to continue. Only then additional injections are supplied. At 3 months response to PCSK9i is evaluated. Therapy is continued in patients with good response and adherence.
This approach is more likely to improve adherence to therapy and reduced wastage. All necessary monitoring of blood tests would be done before, during and after initiating therapy as agreed by the drafted pathway (see enclosed).
Outcomes for the first 50 patients referred to clinic
- 80% of patients were referred by cardiologists, 18% by lipidologists and 2% by primary care. Mean age was 61yrs (range 38-79), and 61% were men.
- Using NICE criteria, 50% of patients with established cardiovascular (CV) disease were classed as very high risk, and 30% were high risk. Of the 20% without established CV disease, most had familial hypercholesterolaemia (FH) or suspected FH.
- Initiating PCSK9i
- 25 (50%) of all referred patients fulfilled NICE’s PCSK9i initiation criteria; 23 (46%) patients consented.
- Mean baseline total cholesterol (TC) for patients started on PCSK9i was 7.8mmol/L and LDL-C was 5.4mmol/L.
- Only 30% of those initiated were taking statins; the rest were labelled as statin intolerant.
- Response to PCSK9i
- At 3 months mean TC was 4.7 (39% reduction), and LDL-C was 2.4 (-54%).
- Those on PCSK9i + statin had greater reduction in LDL-C vs. those on PCSK9i monotherapy (69% vs. 51% reduction, respectively).
- Two patients on PCSK9i monotherapy (9%) had <35% reduction in LDL-C and the addition of Ezetimibe provided a further 15% reduction in LDL-C.
- Due to possible adverse drug reactions (ADR), two patients were switched from Evolocumab to Alirocumab 75mg (with good outcome). Four (17%) stopped treatment altogether due to assumed ADR & non-adherence.
- At 12 months mean TC was 4.2 (46% reduction) and LDL-C was 1.9 (64% reduction).
- Tolerability & Side Effects
- Most commonly reported Adverse Drug Reactions (ADRs) with PCSK9i were: injection site reactions, rhinitis, fatigue & lethargy which were transient and occurred within the first month of treatment.
- Outcome for patients not suitable for PCSK9i
- The rest of the 27 patients were not suitable or declined PCSK9i.
- 13 of those were tolerant to a statin and their therapy was optimised by adding ezetimibe ± switching to high intensity statin, or no change (LDL-C was acceptable).
- Out of the 14 who were intolerant to statins 8 (57%) were started on a tolerable regimen of statins.
Key learning points
- This service provides state of the art patient-centred care and enables us to meet the individual needs of patients with cardiovascular disease or those at high risk of developing CVD.
- Collaboration was key in developing this service. The clinic is an excellent example of collaborative working between different specialities (cardiology, endocrinology and pharmacy) within the Trust and various healthcare professionals as well as primary care. This service is expected to reduce CV death, non-fatal MI, stroke and all-cause death in the population treated.
- Excellent use of skills and the independent pharmacist prescribing to improve access to PCSK9i and optimisation of lipid lowering therapies.
- A specialist centralised service supported by a multidisciplinary team. It constitutes a hub for all patients in Leeds who might be potential candidates for PCSK9i therapy.
- Agreed guidelines and pathways were important for the development of the service.
- The structure and robustness of the service gave commissioners confidence that PCSK9i will be prescribed appropriately and monitored efficiently. This made the approval process smoother.
- High level of education and ongoing support for people prescribed the PCSK9 inhibitors to maintain adherence and effective use.
- Keeping a registry of patients to support monitoring of patients outcomes and the service.
- Regularly seek patient experience feedback to ensure the service is meeting the needs of patients.
- Prescribing from secondary care is cheaper than prescribing it in primary care. Plan for long term prescribing from secondary care.