Discussion
We have developed a novel, person-centred, centralised, multidisciplinary clinic for the assessment and follow-up of patients potentially eligible for PCSK9i therapy. The model ensures that individuals are assessed by relevant specialists in secondary care, and only those meeting NICE criteria13 14 are initiated on a PCSK9i. Data from the first 100 patients suggest that the model is suitably discerning—only around half of those referred were ultimately offered a PCSK9i.
Appropriate patient selection for PCSK9i treatment is particularly important given their high cost and the overall burden of education and monitoring. This aligns with current international guidelines from Europe2 and the USA,20 which advise restricting their use to appropriately selected patients at high risk in order to optimise economic value. Once a PCSK9i is initiated at our centre, patient follow-up, monitoring and support are actively undertaken within the clinic framework. This may help to maximise benefit, bolster adherence and reduce medicines wastage.
Access to PCSK9is has become a key priority in the UK after figures showed that initial uptake was disappointing: around 70% lower than expected over the first 2 years.21 Recent Europe-wide data from the DA VINCI observational study also showed low use of PCSK9is, even though it was associated with increased achievement of LDL-C goals.22 This suggests that many patients are missing out on effective treatment. The UK AAC—which brings together the NHS, government and industry to remove barriers to the uptake of novel medicines—has selected PCSK9i treatment as a focus area.23 The role of the AAC is to facilitate increased adoption, optimised process development, and the generation of real-world data. The LTHT model supports these goals.
Specific barriers to PCSK9i use highlighted by the AAC include21 23: limited and inconsistent access pathways; lack of incentives and initiatives driving cholesterol management; lack of routine recording of LDL-C levels required to initiate a PCSK9i; restricted prescribing, leading to long waiting times; and limited awareness among healthcare professionals of the unmet need that can be addressed with PCSK9is. Our model has the potential to address all of these barriers, and indeed has already successfully eradicated some within our centre.
The multidisciplinary nature of the service is valuable in allowing all relevant healthcare professionals to contribute to lipid management. Nonetheless, on a day-to-day basis, it is led by pharmacist prescribers (consultant and advanced), with consultant cardiologists and lipidologists available when needed. Respondents to the patient feedback questionnaire expressed no dissatisfaction with this arrangement. Importantly, the pharmacist-led model frees up time in cardiology and lipidology clinics, creating greater outpatient capacity. Pharmacist-led PCSK9i provision has previously been successfully implemented at centres in the USA.24 25 The focus of these US pharmacy models was on screening for eligibility, recommending alternative lipid-lowering therapies for ineligible patients, facilitating insurance claims and delivery of PCSK9i supply. In our model, pharmacists reviewed patients in clinic, prescribed PCSK9i and other lipid-lowering therapies, monitored for safety and efficacy, and closely followed up patients to address concerns, support adherence and further optimise lipid-lowering therapy where needed; treatment response and patient satisfaction with the service were formally evaluated. We have also successfully deployed a similar pharmacist-led model of medicines optimisation in patients with post-myocardial infarction.26
Our real-world data suggest that PCSK9i therapy was effective, leading to large and sustained reductions in total and LDL-C. In patients treated for 12 months, mean LDL-C levels fell from 5.0 mmol/L to 2.1 mmol/L, substantially closer to the target levels proposed in international guidelines.2 Furthermore, with regard to NICE targets, 79% of patients with FH (both primary and secondary prevention) achieved a ≥50% reduction in LDL-C, and 91% of patients with non-FH (secondary prevention) attained a >40% reduction in non-HDL-C. Achievement of ESC targets was somewhat lower (37% in patients at high risk and 40% in patients at very high risk) demonstrating that these are more challenging to achieve. Patients who could not meet either NICE or ESC targets were mainly on PCSK9i monotherapy. These findings show that meeting NICE and ESC targets requires the use of multiple lipid lowering therapies concomitantly.
There were no major safety concerns with PCSK9i therapy, and <10% of patients experienced (transient) musculoskeletal pain even though some had experienced such symptoms with prior statin therapy. This aligns with data from the GAUSS-3 trial, which showed modest rates of musculoskeletal AEs—and very few resulting discontinuations (<1%)—in patients with muscle-related statin intolerance who were then initiated on evolocumab.27
Our clinic also offers medicines optimisation and adherence support in PCSK9i-ineligible patients. This includes issues around statin intolerance, and many individuals were able to restart statin therapy having previously been considered intolerant. There are data to suggest that stopping and then re-initiating statins can result in improved tolerance. For example, in a study of 11 124 patients in whom statins were discontinued at least temporarily because of clinical events or symptoms believed to have been caused by statin use, 92% of those who were rechallenged were still taking a statin 12 months after the initial event.8
Overall patient satisfaction with the clinic model and PCSK9i therapy was high. Questionnaire respondents who initiated a PCSK9i were almost all happy with the drug and felt that it fulfilled its purpose. Furthermore, irrespective of PCSK9i prescribing, clinic attendees agreed that they felt listened to, were provided with clear lipid-lowering plans, and would recommend the service to others. The clinic model aligns with local and international guidance on person-centred care and shared decision-making.28 29
Our model was considered to be cost effective by the commissioners for multiple reasons:
The prescribing of PCSK9i in secondary care under the patient access scheme (as per NICE13 14) provided a discount on the cost of PCSK9i injections.
It reduced wastage of PCSK9i by providing limited supply and following patients regularly.
The service supported improved adherence to PCSK9i (although there is potential for adherence to decrease in the long term).
It improved the lipid management of patients who were not eligible for PCSK9i, thus providing additional lipid-lowering benefit.
Overall, the service succeeded in lowering LDL-C among PCSK9i-treated patients by an average of around 3 mmol/L. If these reductions are maintained, they would be expected to bring important clinical benefits, with a stepwise decrease in atherosclerotic CVD risk as LDL-C is reduced. Indeed, it has been estimated that each 1 mmol/L reduction in LDL-C is associated with a 22% relative risk reduction for major vascular events.30
Because the NICE threshold for initiating PCSK9i is higher (our patients had a mean baseline LDL-C of 5.0±1.6 mmol/L), we would expect favourable cost effectiveness based on the findings of the ODYSSEY OUTCOMES cost-effectiveness analysis for PCSK9i, which found it to be cost effective in patients with an LDL-C ≥2.6 mmol/L.31
We should acknowledge the limitations of this study. The sample size was small and only around half were offered PCSK9i, so care should be taken in extrapolating to larger populations. Furthermore, the study design was retrospective and had no comparator arm. A prospective, randomised controlled trial would be valuable. In addition, not all patients completed the feedback questionnaire and those that did so may have been somewhat self-selecting for greater satisfaction with the service. Nonetheless, the response rate was acceptable and the questionnaire results align with wider anecdotal opinions.
Overall, the data suggest that our innovative, centralised, pharmacist-led, multidisciplinary clinic can be successfully employed to select patients for PCSK9i therapy—and drive long-term monitoring, adherence and ultimately LDL-C lowering. Importantly, the service also addresses statin intolerance and provides appropriate medicines optimisation and adherence assistance even in PCSK9i-ineligible patients. The model is flexible enough to allow the introduction of other novel medications for cholesterol lowering, and this is now happening following the recent incorporation of bempedoic acid and inclisiran into the clinical pathway. These new agents have been shown to significantly reduce LDL-C,32 but outcomes data have not yet been reported.
In line with the goals of the AAC, our model could be duplicated elsewhere in the country to support better uptake and optimisation of PCSK9is and other novel treatments.