PCSK9 inhibitors for lipid-lowering treatment in patients with atherosclerotic cardiovascular disease: a health technology assessment

Abstract

Background In multiple countries, clinical guidelines recommend proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for lowering low-density lipoprotein cholesterol (LDL-C) in individuals with atherosclerotic cardiovascular disease (ASCVD). Comprehensive comparisons of the efficacy, safety, and cost-effectiveness across different PCSK9 inhibitors remain limited, and current evidence requires updating. To address this gap, this study applies a health technology assessment framework to systematically evaluate the use of PCSK9 inhibitors in patients with ASCVD. Methods A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted from database inception to February 28, 2026 to identify randomized controlled trials (RCTs) comparing PCSK9 inhibitors with standard care (statins with or without ezetimibe) in patients with ASCVD. Both pairwise and network meta-analyses were applied to synthesize direct and indirect evidence. Trial sequential analysis (TSA) was performed to evaluate the sufficiency of the accumulated data. In addition, a Markov model was developed from the perspective of the Chinese healthcare system to assess the cost-effectiveness of PCSK9 inhibitors in ASCVD patients. Results In total, 24 RCTs comprising 63,328 participants were included. The results of TSA and network meta-analysis showed that, compared with SOC, all three PCSK9 inhibitors significantly reduced LDL-C levels. No statistically significant differences were found for stroke outcomes. However, both alirocumab and evolocumab significantly reduced the risk of non-fatal myocardial infarction. None of the three PCSK9 inhibitors was associated with an increased risk of serious adverse events. Using the meta-analysis findings and data from the Chinese healthcare system, the incremental cost-effectiveness ratios (ICERs) for alirocumab, evolocumab, and inclisiran versus standard care were estimated at USD 12,791.07/QALY, USD 11,646.38/QALY, and USD 31,730.14/QALY, respectively. In a scenario analysis incorporating a 72.1% reduction in the price of inclisiran, its ICER decreased to USD 9,686.31/QALY. The one-way sensitivity analysis showed that the discount rate exerted the greatest influence on model outcomes. In the price-reduction scenario, probabilistic sensitivity analysis indicated that inclisiran had a 96.6% probability of being cost-effective at a willingness-to-pay threshold of USD 13,410/QALY. Conclusion Currently, evolocumab demonstrates relative advantages in lipid-lowering efficacy, cardiovascular outcomes, and economic value for patients with ASCVD. Alirocumab represented a cost-effective alternative. In the scenario analysis incorporating a 72.1% reduction in the price of inclisiran, inclisiran became a potentially highly cost-effective option in the Chinese healthcare setting.