Systematic review of pharmacoeconomic evaluation on PCSK9 inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia / 中国药房

OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia， and to provide a reference for clinical treatment， health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI， the pharmacoeconomic literature about PCSK9 inhibitors （evolocumab and alirocumab） for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8， 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） scale. The descriptive analysis was performed for basic information， model structure， related parameters， sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included， with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system， payer and societal perspective. The effectiveness and utility data mainly came from the previous studies； the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year， while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome， myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups， such as patients with triple vessel disease， patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design， and strive to select large-scale， high-quality data to enhance the quality of reports and the transparency of health decisions， so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.

Effectiveness，Safety and Economy of Evolocumab in the Treatment of Hypercholesterolemia ：A Rapid Health Technology Assessment / 中国药房

OBJECTIVE：To rapidly evaluate the effectiveness ，safety and economy of evolocumab in the treatment of hypercholesterolemia so as to provide evidence-based reference for clinical drug selection and decision. METHODS ：Retrieved from PubMed，Cochrane Library ，CNKI，Wanfang database and HTA relative official website ，HTA reports ，systematic evaluation/ Meta-analysis and pharmacoeconomic studies about evolocumab alone or combined with standard plan versus standard plan or placebo or ezetimibe in the treatment of hypercholesterolemia were collected during the inception to Jan. 2020. Based on literature screening and data extraction ，HTA checklist ，system evaluation measurement tool AMSTAR- 2 scale，comprehensive healthy economic evaluation report standard scale were used to evaluate the quality of included HTA reports ，systematic evaluation/ Meta-analysis and pharmacoeconomic literatures. Quantitative description was performed for effectiveness and safety results ，and qualitative description was performed for economic evaluation results. RESULTS ：A total of 13 literatures were included ，involving 6 Meta-analysis and 7 economic studies. The quality of Meta-analysis literatures was low ，and the quality of economic research was good. In terms of effectiveness ，compared with placebo or ezetimibe ，evolocumab significantly reduced the levels of LDL-C ，TC， TG and VLDL-C ，the incidence of cardiovascular events ，myocardial infarction ，coronary ischemia and stroke ，while increased the level of HDL-C （P＜0.05）. There was no statisti cal significance in the risk of hospitalizatio n，cardiac mortality or cardiovascular disease mortality in patients with unstable angina pectoris between placebo and evolocumab （P＞0.05）. In terms ofsafety，there was no significant difference in the incidence of 6237545。E-mail：zhangxu1130@163.com any adverse events ，any treatment emergency adverse events and back pain ，musculoskeletal and connective tissue diseases between evolocumab and placebo （P＞0.05）. In terms of economy，additional use of evolocumab ，based on standard plan ，had a cost-effectiveness advantage for patients with high-risk atherosclerotic cardiovascular disease （ASCVD）whose blood lipids were still not up to standard. CONCLUSIONS ：Evolocumab has good effectiveness and safety in the treatment of hypercholesterolemia. For high-risk patients with ASCVD whose blood lipids are still not up to standard after standard plan ，evolocumab has certain economy and can be used as an alternative.

Pharmacological Strategies beyond Statins: Ezetimibe and PCSK9 Inhibitors

Dyslipidemia, highly elevated, low-density lipoprotein (LDL) cholesterol, is a major cardiovascular risk factor. Statins have been proven to effectively reduce the risk of atherosclerotic cardiovascular disease (ASCVD) and are recommended as a first-line therapy for the primary and secondary prevention of ASCVD. However, statins may not be sufficient in decreasing LDL cholesterol levels and pose a significant on-treatment residual risk of major cardiovascular events (i.e., residual cholesterol risk) according to meta-analyses of statin trials. Current guidelines for cholesterol management to achieve additional LDL cholesterol reduction and reduce ASCVD risk recommend two hyperlipidemic agents besides statins. Use of ezetimibe, a cholesterol absorption inhibitor, leads to additional LCL cholesterol reduction and decreased ASCVD risk, when added to statin therapy, without raising significant safety concerns. Furthermore, in combination with a mild-to-moderate statin intensity, ezetimibe is used in situations of statin-associated adverse effects such as myalgia and the combination therapy is relatively safer. Monoclonal antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), alirocumab, and evolocumab, have been approved to lower LDL cholesterol level. While there are drawbacks to the use of PCSK9 inhibitors, including high cost and adverse events such as injection site reaction, they significantly decreased serum LDL cholesterol levels and thereby ASCVD risks when added to maximally tolerated statin therapy.

Inhibición de PCSK9: una nueva alternativa para reducir el colesterol y prevenir la enfermedad cardiovascular aterosclerosa / Inhibition of PCSK9: a new alternative for cholesterol reduction and prevention of atherosclerotic cardiovascular disease

Resumen La enfermedad cardiovascular aterosclerosa ocupa el primer lugar mundial en morbilidad y mortalidad. El principal factor de riesgo de enfermedad es el colesterol unido a lipoproteínas de baja densidad (C-LDL). El tratamiento farmacológico de elección para reducir el C-LDL son las estatinas; sin embargo, han sido insuficientes para eliminar el riesgo cardiovascular, especialmente en pacientes con formas primarias de hipercolesterolemia relacionadas con mutaciones genéticas, o intolerantes a estatinas. Es de gran importancia el desarrollo de nuevos fármacos para abatir el riesgo que persiste a pesar de la administración de estatinas. La proconvertasa subtilisina-kexina 9 (PCSK9) es un regulador primordial de la cantidad de receptores de LDL, ya que su función es dirigir dichos receptores a su destrucción lisosomal. El advenimiento de anticuerpos monoclonales para bloquear la PCSK9 ha permitido mejorar la cantidad y eficiencia de los receptores de LDL, de esto resulta la disminución notable del colesterol circulante. Hasta el momento, la eficacia e inocuidad de estos anticuerpos resultan aceptables, y los datos preliminares en cuanto a su efecto en la reducción de la morbilidad y mortalidad cardiovasculares son alentadores.

Abstract Atherosclerotic cardiovascular disease represents the leading cause of morbidity and mortality in most countries. The main risk factor for developing this disease is low density lipoprotein cholesterol (LDL-C). The pharmacological treatment of choice for reducing LDL-C is statins; however, in spite of the widespread use of statins, these drugs have been insufficient to eliminate cardiovascular risk. This residual risk is most relevant in patients with primary forms of hypercholes-terolemia associated with genetic mutations, or in those who are intolerant to statins. The development of new drugs to reduce residual cardiovascular risk is of vital importance. Proprotein convertase subtilisin-kexin 9 (PCSK9) is an important regulator of the amount of LDL receptors since its function is to direct these receptors to their lysosomal destruction. The development of monoclonal antibodies to block extracellular PCSK9 has allowed us to improve the quantity and efficiency of LDL receptors, resulting in a significant decrease in plasma cholesterol. Efficacy and safety of these antibodies is currently considered acceptable and preliminary data are encouraging but still insufficient to assess the favorable impact of these antibodies in reducing cardiovascular morbidity and mortality.

Research progress in proprotein convertase subtilisin/kexin type 9 monoclonal antibody / 中华临床营养杂志

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in lipid reg-ulation through interaction with low-density lipoprotein cholesterol receptors , and several types of PCSK 9 inhibi-tors are gradually becoming research hotspots due to their lipid lowering effect .Among them PCSK9 monoclonal antibodies are the closest to clinical application , and a number of phase Ⅲclinical trials in PCSK9 monoclonal antibodies have been completed in recent years .We systemically reviewed the current clinical research on PC-SK9 monoclonal antibodies in this paper , in order to understand their efficacy and long-term safety in reducing the risk of cardiovascular diseases .