Odingo, Myron Oluoch ORCID: https://orcid.org/0000-0002-2641-2973 (2021) A multi-methods study of the factors influencing the adoption of proprotein convertase subtilisin/kexin-type 9 (PCSK9) inhibitors. Doctoral thesis, Keele University.

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Abstract

Introduction
A new class of lipid lowering agent Proprotein Convertase Subtilisin/Kexin Type 9 inhibitors (PCSK9) was launched in 2015 for the treatment of heterozygous familial hypercholesterolemia (HeFH) in combination with statin therapy. There appeared to be a relatively slow uptake of PCSK9 inhibitors. The first aim of the study was to examine clinical attributes associated with reduction in low-density lipoproteins cholesterol (LDLC) among HeFH patients, while the second aim was to explore the factors influencing the use of PCSK9 inhibitors in clinical practice.

Methods
The quantitative phase of the study used logistic regression to investigate HeFH clinical attributes from the Clinical Practice Research Datalink (CPRD) database (n=5134) in relation to a final LDLC level of 5 mmol/l; which is the threshold for PCSK9 inhibitor eligibility for HeFH. The qualitative phase of the project involved 17 in-depth semi structured interviews to explore stakeholder perceptions of the factors influencing the use of PCSK9 inhibitors.

Results
LDLC levels featured prominently in the results of both phases of the study. Quantitative analysis showed that 18% of HeFH patients did not meet the 5mmol/l threshold for PCSK9 inhibitor eligibility even though they did not achieve the guideline recommended treatment target of 50% LDLC reduction with statin therapy. Lipid consultants perceived the eligibility threshold as an inhibitor of prescription in these cases. There was also an issue with LDLC levels not being recorded; 48% of HeFH patients in the CPRD dataset did not have a record of LDLC. In the clinical setting, this had the effect of delaying PCSK9 inhibitor prescription when evidence of multiple LDLC readings meeting the prescription threshold was required. In primary care, GPs suggested that nurses could increase the recording of LDLC records because they had first contact with patients while performing health checks. Overall, low awareness of HeFH was associated with low rates of referral to secondary care for PCSK9 inhibitor consideration. Facilitators of PCSK9 inhibitor use included support from pharmaceutical companies who provided educational material for PCSK9 inhibitor use. Patients were also perceived to engage with treatment when they understood that HeFH could cause cardiac events.

Conclusions
This study found that LDLC records were critical to the prescription of PCSK9 inhibitors. In the quantitative analysis the clinical attributes of maximum LDLC on record, age and lipid medication use were statistically associated to LDLC achievement. It was however not possible to predict PCSK9 inhibitor eligibility; further work would involve the addition of clinical attributes such as lipoprotein (a) to the model analysis. PCSK9 inhibitor prescription was perceived to be hindered by inadequate recording of LDLC records. Consultants also reported that the LDLC thresholds for eligibility were restrictive in some cases. LDLC is an important determiner of PCSK9 inhibitor use; improved LDLC recording and evaluation of LDLC thresholds may be necessary in efforts to optimise PCSK9 inhibitor use.

Item Type: Thesis (Doctoral)
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Contributors: Chapman, SR (Thesis advisor)
Frisher, M (Thesis advisor)
Depositing User: Lisa Bailey
Date Deposited: 24 Mar 2021 09:32
Last Modified: 24 Mar 2021 09:32
URI: https://eprints.keele.ac.uk/id/eprint/9295

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