Fair pricing, fair access; a systematic review of cost-effectiveness of new hyperlipidemia injectable medication in...

Lipid-lowering therapy is central to cardiovascular disease (CVD) management. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors (alirocumab, evolocumab) and inclisiran offer greater low-density lipoprotein cholesterol (LDL-C) reduction and improved outcomes beyond statins and ezetimibe, but high costs raise affordability concerns in low- and middle-income countries. This study reviews their cost-effectiveness in developing settings.

PubMed, Scopus, Web of Science, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to March 1, 2024. Studies were assessed for Quality-Adjusted Life Years (QALYs), Life Years Gained (LYGs), costs, and "Incremental Cost-Effectiveness Ratios" (ICERs). Quality and bias were evaluated using the "Integrated Health Economic Evaluation Reporting Standards" (CHEERS) and ECOBIAS checklists, following "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines.

Of 580 records, 13 studies (2019-2024) from China (n = 8), Thailand, Mexico, Taiwan, Qatar, and Saudi Arabia met inclusion criteria, mostly evaluating evolocumab for primary and secondary prevention using Markov models (Time horizon: 2 years -lifetime, Discount rates: 3-5%). Studies were generally from a healthcare perspective. Evolocumab was not cost-effective in Chinese post-myocardial infarction (MI) patients (ICERs up to $281,762/QALY) but favorable in familial hypercholesterolemia(FH) ($57,018/QALY), and when evolocumab added to statins was cost-effective in patients with acute MI ($7,819 to $61,242 per QALY) and acute coronary syndrome (ACS) (vs. ezetimibe + statins) ($26,110/QALY) and atherosclerotic cardiovascular disease (ASCVD) (vs. placebo + statins)($4,268/QALY). Alirocumab ($490,198/QALY) and inclisiran ($335,404.88/QALY) were not cost-effective, while ezetimibe was ($22,965/QALY). In Thailand, PCSK9 inhibitors ($1,496,139/QALY), and ezetimibe ($33,246/QALY) exceeded thresholds. Evolocumab was cost-effective in Mexico ($37,925/QALY-$44,346/QALY) and Saudi Arabia ($49,502/QALY-$71,968/QALY) but not in Qatar. Sensitivity analyses identified drug prices, event risks, and utilities as key ICER drivers, with probabilistic analyses showing low cost-effectiveness in China (~ 2%) but higher in high-risk groups or at elevated thresholds.

Cost-effectiveness of PCSK9 inhibitors and inclisiran varies across developing countries, driven by drug prices, WTP thresholds, and healthcare perspectives. Evolocumab may be cost-effective in high-risk subgroups or in Mexico and Saudi Arabia but remains largely unaffordable elsewhere. Ezetimibe was consistently more favorable. Price reductions, tiered pricing, pooled procurement, and context-specific thresholds are essential to improve access and equity.