Bhavani Shankara Bagepally1, Akhil Sasidharan2. 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. bagepally.bs@gov.in. 2. Health Technology Assessment Resource Centre, ICMR-National Institute of Epidemiology, R-127, Tamil Nadu Housing Board, Phase I and II, Ayapakkam, Chennai, 600077, India.
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. PROSPERO REGISTRATION: ID CRD42020206043.
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.
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