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

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Abstract

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.

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We received no specific funding for this work. However, the Dept. of Health Research Govt. of India funds the Health Technology Assessment resource center ICMR-NIE. Funders had no role in the conceptualization, conduction, and manuscript preparation.

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  1. Health Technology Assessment Resource Centre, ICMR-National Institute of Epidemiology, R-127, Tamil Nadu Housing Board, Phase I and II, Ayapakkam, Chennai, 600077, India

    Bhavani Shankara Bagepally & Akhil Sasidharan

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  1. Bhavani Shankara Bagepally
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Bagepally BS: conceptualization, data curation, formal analysis, investigation, methodology, software, original draft, review and editing. Akhil Sasidharan: data curation, formal analysis, original draft.

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Bagepally, B.S., Sasidharan, A. Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies. Eur J Clin Pharmacol 78, 351–363 (2022). https://doi.org/10.1007/s00228-021-03242-6

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