Potential barriers in lipid-lowering treatment with PCSK9 inhibitors from a healthsystem perspective. Comparative evidence from ten countries

Abstract

Background: Gaps between clinical guidelines and attainment of LDL-C goals are evident across jurisdictions. Despite strong evidence of benefit from PCSK9-inhibitors (PCSK9i) treatment in eligible patients, significant underuse remains, suggesting considerable unmet need in clinical outcomes optimization. Purpose: We investigated key performance endpoints across 10 countries to provide a comparative assessment of potential barriers in PCSK9i therapeutic integration from a healthcare system perspective. Methods: We performed secondary analysis of peer-reviewed literature, health technology assessment reports, guidelines, clinical pathways since 2015 and constructed a comparative framework of pre-defined endpoints for 10 study countries (Japan, Italy, Spain, Australia, Canada, United Kingdom, Germany, France, Netherlands, USA). We identified 8 endpoints, which were clustered in 3 domains: (a) healthcare system characteristics, (b) demand-side policies, (c) medicine reimbursement policies, pertaining to cost-sharing. Approved PCSK9i indications were in scope. Results: PCSK9i are reimbursed in all countries. Prescribing restrictions have been applied in all countries (Table 1). PCSK9i for primary prevention are reimbursed mainly in familial hypercholesterolemia, while additional criteria may apply depending on country and condition. PCSK9i are: (a) reserved mainly for very high- or high-risk cohorts (Japan, UK, Netherlands); (b) reimbursed for secondary prevention when additional risk factors/comorbidities exist (Australia, Germany, Netherlands); (c) recommended as 3rd line in 6 countries, as 2nd line in 3 and alone or in combination with other therapies in the USA; and (d) restricted to specialist prescribing while general practitioners cannot initiate treatment in 6 countries, potentially increasing waiting times and underuse rates. Follow-up periods may apply prior to establishing eligibility and vary from 3-12 months, while prior authorization/eligibility documentation may be necessary adding to administrative burden. Age criteria may apply in determining or continuing reimbursement (e.g. max 80 years in Italy). Regional and insurance plan variations apply in Canada and USA, respectively. LDL-C reimbursement thresholds are applied in 7 countries. Their relevance to guidelinerecommended goals suggests potential underuse gaps (Fig. 1). While no threshold applies in Germany, an additional criterion of indication for LDLapheresis determines eligibility. Cost-sharing ranges between 0-30% in co-insurance models, may include a flat fee, a deductible or combination of these. Conclusion: Restrictions in the use of PCSK9i from marketing authorization labels are implemented in all 10 countries and differ across key endpoints. Significant differences exist between guideline-recommended LDLC goals and reimbursement thresholds, while additional prescribing and documentation restrictions apply over reimbursed indications, contributing to potential underuse.