The incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: A Systematic Review and Meta-analysis of cost-utility studies

Abstract

Introduction: Proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) are monoclonal antibodies that lower lipid levels by inhibiting PCSK9. Although several cardiovascular outcome trials reported beneficial clinical effectiveness of PCSK9i, the evidence on cost-effectiveness is mixed. We systematically reviewed the evidence on cost-effectiveness and synthesized incremental net benefit (INB) to quantify the pooled cost-effectiveness of PCSK9i lipid-lowering therapy. Methods: We systematically searched for full economic evaluation studies reporting outcomes of PCSK9 inhibitors compared with any other lipid-lowering pharmacotherapies. We searched PubMed, Embase, Scopus, and Tufts Registry for eligible studies up-to September 2020, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We pooled the INB with a 95% confidence interval using a random-effects model. We assessed the Heterogeneity using the Cochrane-Q test and I2 statistic. We used the modified economic evaluations bias (ECOBIAS) checklist to evaluate the quality of the selected studies.Results: A total of 20 studies were eligible, mainly from high-income countries (HIC). The pooled INB of PCSK9i versus other lipid-lowering pharmacotherapies were estimated from n=21 comparisons; with high heterogeneity (I2=98.04). The INBp (95% CI) was US$ -46,665 (-196,203; 102,874), PCSK9i was found to be not cost-effective when compared with other standard therapies; however, this finding was not statistically significant. On subgroup analysis PCSK9i was significantly not cost-effective [US$ -25,686 (-26,085;-25,287), I2=0] compared to other lipid-lowering pharmacotherapies among HICs, with payers perspective [US$ -25,686 (-26,086;-25,287), I2=0] and with higher discount rates of 5% for cost [US$ -25,686 (-26,086;-25,287), I2=0]. The sensitivity analysis revealed the subgroup findings are not robust.Conclusion: PCSK9is’ 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

Cost-effectiveness of Ezetimibe plus statin lipid-lowering therapy: A systematic review and meta-analysis of cost-utility studies

“…We followed the data preparation method and analysis described and used elsewhere 23, 33, 36, 37 . To calculate the INB and its variance, mean values along with dispersions (SD, SE, and 95% CI) of ΔC and ΔE are required.…”

“…A favourable tolerability profile, ease of use, and affordability make Ezetimibe a better option than PCSK9i 22 . Furthermore, a recent meta-analysis of cost-utility studies (CUA) showed PCSK9i to be not cost-effective compared to other lipid-lowering therapeutic agents in high-income countries (HICs) 23, 24 . As a result, Ezetimibe can be used as a next-cholesterol medication.…”

Advancements In Pharmacotherapy for Hyperlipidemia: A Comprehensive Review of Recent Drug Innovations and Clinical Outcomes

“…68 Health economic analyses are essential for evaluating the value of PCSK9 inhibitors to their clinical benefits. 69 The mechanism of action of PCSK9 inhibitors is shown in Figure 5.…”