Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies.

INTRODUCTION: Proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) are monoclonal antibodies that lower lipid levels. Although several cardiovascular outcome trials reported the effectiveness of PCSK9i, the evidence on cost-effectiveness is mixed. We systematically reviewed the evidence and synthesized incremental net benefit (INB) to quantify pooled cost-effectiveness. METHODS: We systematically searched for full economic evaluation studies reporting outcomes of PCSK9i compared with other lipid-lowering pharmacotherapies. We searched PubMed, Embase, Scopus, and Tufts Registry for eligible studies up to August 2021, adhering to preferred reporting items for systematic reviews and meta-analyses guidelines. We pooled INB in US$ with a 95% confidence interval using a random-effects model. We assessed heterogeneity using the Cochran Q test and I2 statistics. We used the modified economic evaluations bias (ECOBIAS) checklist to evaluate the quality of selected studies. RESULTS: Twenty-three studies were eligible, mainly from high-income countries (HIC). The pooled INB (INBp) of PCSK9i versus other lipid-lowering pharmacotherapies were estimated from n = 24 comparisons, with high heterogeneity (I2 = 99.99). The INBp (95% CI) was $ - 78,207 (- 120,422; - 35,993) or € - 52,526 (- 80,879; - 24,174) (conversion factor 1 US$ = 0.67€) which shows that PCSK9i was not significantly cost-effective when compared to other standard therapies. On subgroup analysis PCSK9i was significantly not cost-effective [$ - 23,672 (- 24,061; - 23,282)] compared to other lipid-lowering pharmacotherapies in HICs, upper-middle-income countries [$ - 158,412 (- 241,738; - 75,086)] or when the target population was CVD [$ - 109,343 (- 158,968; - 59,717)]; and for treatment subgroup: against placebo or no treatment [$ - 79,018 (- 79,649; - 78,388 PCSK9)] and standard statin therapies [$ - 131,833 (- 173,449; - 90,216)]. The sensitivity analysis revealed that the findings are not robust for HICs and the treatment subgroups. CONCLUSION: PCSK9 inhibitors are not cost-effective compared to other lipid-lowering pharmacotherapies in HICs. Further, current pieces of evidence are predominantly from HICs with largely lacking evidence from other economies. PROSPERO REGISTRATION: ID CRD42020206043.

Patient Characteristics and Treatment Patterns among Medicare Beneficiaries Initiating PCSK9 Inhibitor Therapy.

PURPOSE: There is limited real-world evidence around use of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) among US older adults. This study examined baseline characteristics of fee-for-service (FFS) Medicare beneficiaries newly initiating PCSK9i therapy during the period immediately following market availability. METHODS: This cross-sectional study used Medicare claims (2013-2016) to identify 5051 FFS Medicare beneficiaries who filled ≥ 1 PCSK9i prescription between August 2015 and December 2016. We analyzed patient demographics, clinical characteristics, and baseline healthcare expenditures in the 12-month period prior to PCSK9i initiation, for these beneficiaries. RESULTS: Most beneficiaries initiating PCSK9i were female (57%), < 75 years of age (61%), white (89%), and lived in metropolitan areas (83%). At baseline, these PCSK9i initiators had 6 chronic conditions on average, with conditions such as hyperlipidemia, hypertension, and ischemic heart disease being most prevalent. Approximately 88% had a diagnosis of atherosclerotic cardiovascular disease (ASCVD), and 14% experienced acute cardiovascular events during the 12-month baseline period. Use of any statin and/or ezetimibe ranged from 54 to 76% in the 6-month and 24-month baseline period. Their total annual Medicare expenditures averaged US$17,552, of which most were attributable to ambulatory care and prescription use, in the 12-month baseline period. CONCLUSION: High burden of cardiovascular conditions and prescription expenditures at baseline were common among FFS beneficiaries initiating PCSK9i therapy. These findings suggest that physicians prescribe PCSK9i to elderly patients at high risk for adverse cardiovascular events. Considering the evolving treatment landscape, PCSK9i utilization might increase in Medicare.

Cost-Effectiveness of Evolocumab Therapy for Myocardial Infarction: The Chinese Healthcare Perspective.

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an indispensable lipid-lowering treatment option, but their cost-effectiveness has been questioned. This study aimed to perform a health economic evaluation of evolocumab versus placebo in patients with myocardial infarction (MI) in China. METHODS: A Markov cohort state-transition model was developed in decision analysis software to estimate the incremental cost-effectiveness ratio (ICER), defined as cost per quality-adjusted life-year (QALY) saved. The simulation subjects could undergo non-fatal MI and/or stroke, or vascular or non-vascular death event. We integrated the Chinese population-specific demographics and event rates with the risk reduction of evolocumab based on the FOURIER trial and/or lowering of low-density lipoprotein cholesterol (LDL-C). Age-related change, event costs and utilities were included from published sources. RESULTS: At its current list price [33,748 Chinese yuan (CNY) annually per person], the ICER for evolocumab therapy was 927,713 CNY per QALY gained when integrating the FOURIER trial with absolute reduction of LDL-C. The probability of cost-effectiveness of evolocumab versus placebo was 1.96%, with a generally accepted threshold of 212,676 CNY per QALY gained. A reduction in acquisition price by approximately 70% (to less than 10,255 CNY annually) was needed to be cost-effective. Alternative scenario analyses of therapeutic benefit showed that the ICER for evolocumab in MI patients with uncontrolled familial hypercholesterolemia (FH) was 187,736 CNY per QALY gained. CONCLUSION: Evolocumab in patients with MI was not cost-effective based on the price in 2019 in China; however, treatment with evolocumab was more favorable in MI patients with FH.

Trends in Utilization and Cost of Low-Density Lipoprotein Cholesterol-Lowering Therapies Among Medicare Beneficiaries: An Analysis From the Medicare Part D Database.

Importance: Low-density lipoprotein cholesterol (LDL-C)-lowering therapies are a cornerstone of prevention in atherosclerotic cardiovascular disease. With the introduction of generic formulations and the release of new therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, contemporary Medicare utilization of these therapies remains unknown. Objective: To determine trends in utilization and spending on brand-name and generic LDL-C-lowering therapies and to estimate potential savings if all Medicare beneficiaries were switched to available therapeutically equivalent generic formulations. Design, Setting, and Participants: This cross-sectional study analyzed prescription drug utilization and cost trend data from the Medicare Part D Prescription Drug Event data set from 2014 to 2018 for LDL-C-lowering therapies. A total of 11 LDL-C-lowering drugs with 25 formulations, including 16 brand-name and 9 generic formulations, were included. Data were collected and analyzed from October 2019 to June 2020. Main Outcomes and Measures: Number of Medicare Part D beneficiaries, annual spending, and spending per beneficiary for all formulations. Results: The total number of Medicare Part D beneficiaries ranged from 37 720 840 in 2014 to 44 249 461 in 2018. The number of Medicare beneficiaries taking LDL-C-lowering therapies increased by 23% (from 20.5 million in 2014 to 25.2 million in 2018), while the associated Medicare expenditure decreased by 46% (from $6.3 billion in 2014 to $3.3 billion in 2018). Lower expenditure was driven by greater uptake of generic statin and ezetimibe and a concurrent rapid decline in the use of their brand-name formulations. Medicare spent $9.6 billion on brand-name statins and ezetimibe and could have saved $2.1 billion and $0.4 billion, respectively, if brand-name formulations were switched to equivalent generic versions when available. The number of beneficiaries using PCSK9 inhibitors since their introduction in 2015 has been modest, although use has increased by 144% (from 25 569 in 2016 to 62 476 in 2018) and total spending has increased by 199% (from $164 million in 2016 to $491 million in 2018). Conclusions and Relevance: Between 2014 and 2018, LDL-C-lowering therapies were used by 4.8 million more Medicare beneficiaries annually, with an associated $3.0 billion decline in Medicare spending. This cost reduction was driven by the rapid transition from brand-name formulations to lower-cost generic formulations of statins and ezetimibe. Use of PCSK9 inhibitions, although low, increased over time and could have broad implications on future Medicare spending.