Impact of national drug price negotiation policy on the accessibility and utilization of PCSK9 inhibitors in China: an interrupted time series analysis.

BACKGROUND: PCSK9 inhibitors are a novel class of lipid-lowering drugs that have demonstrated favorable efficacy and safety. Evolocumab and alirocumab have been added to China's National Reimbursement Drug List through the National Drug Price Negotiation (NDPN) policy. This study aims to evaluate the impact of the NDPN policy on the utilization and accessibility of these two PCSK9 inhibitors. METHODS: The procurement data of evolocumab and alirocumab were collected from 1,519 hospitals between January 2021 and December 2022. We determined the monthly availability, utilization, cost per daily defined dose (DDDc), and affordability of the two medicines. Single-group interrupted time series (ITS) analysis was performed to assess the impact of the NDPN policy on each drug, and multiple-group ITS analysis was performed to compare the differences between them. RESULTS: The NDPN policy led to a significant and sudden increase in the availability and utilization of PCSK9 inhibitors, along with a decrease in their DDDc. In the year following the policy implementation, there was an increase in the availability, utilization, and spending, and the DDDc remained stable. The affordability of PCSK9 inhibitors in China have been significantly improved, with a 92.97% reduction in out-of-pocket costs. The availability of both PCSK9 inhibitors was similar, and the DDDc of alirocumab was only $0.23 higher after the intervention. The market share of evolocumab consistently exceeded that of alirocumab. Regional disparities in utilization were observed, with higher utilization in the eastern region and a correlation with per capita disposable income. CONCLUSIONS: The NDPN policy has successfully improved the accessibility and utilization of PCSK9 inhibitors in China. However, regional disparities in utilization indicate the need for further interventions to ensure equitable medicine access.

Measuring Costs of Cardiovascular Disease Prevention for Patients with Familial Hypercholesterolemia in Administrative Claims Data.

INTRODUCTION: Familial hypercholesterolemia is a common genetic condition that significantly increases an individual's risk of cardiovascular events such as heart attack, stroke, and cardiac death and is a candidate for population-wide screening programs. Economic analyses of strategies to identify and treat familial hypercholesterolemia are limited by a lack of real-world cost estimates for screening services and medications for reducing cardiovascular risk in this population. METHODS: We estimated the cost of lipid panel testing in patients with hyperlipidemia and the cost of statins, ezetimibe, and PCKS9 inhibitors in patients with familial hypercholesterolemia from a commercial claims database and report costs and charges per panel and prescription by days' supply. RESULTS: The mean cost for a 90-day supply for statins was $183.33, 2.3 times the mean cost for a 30-day supply at $79.35. PCSK9 inhibitors generated the highest mean costs among medications used by patients with familial hypercholesterolemia. CONCLUSIONS: Lipid testing and lipid-lowering medications for cardiovascular disease prevention generate substantial real-world costs which can be used to improve cost-effectiveness models of familial hypercholesterolemia screening and care management.

Análise de Custo-Efetividade da Terapia com Evolocumabe em Pacientes com Alto Risco de Eventos Cardiovasculares no Contexto do SUS - Brasil / Cost-Effectiveness Analysis of Evolocumab Therapy in Patients at High Risk of Cardiovascular Events in the Context of the Brazilian Unified Health System

Resumo Fundamento: Em associação às estatinas, os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) demonstraram ser eficazes na redução de eventos cardiovasculares em pacientes de alto risco. Objetivo: Analisar a custo-efetividade da implementação de evolocumabe para pacientes com alto risco de eventos cardiovasculares no contexto do Sistema Único de Saúde (SUS) no Brasil. Métodos: Um modelo de Markov foi utilizado, baseando-se em uma amostra ambulatorial de pacientes com doença arterial coronariana. Os desfechos primários analisados foram infarto agudo do miocárdio, acidente vascular cerebral isquêmico (AVCi), revascularização do miocárdio e morte cardiovascular. O resultado foi expresso por meio da razão de custo-efetividade incremental (RCEI), considerando-se uma taxa de desconto de 5% ao ano, e uma análise de sensibilidade foi realizada, tendo em vista a imprecisão de valores. Resultados: Selecionaram-se 61 pacientes com risco cardiovascular estimado em 35% em 10 anos, se em uso de atorvastatina 80mg/dia, e em 22,75%, se adicionado o evolocumabe. O custo global por paciente no período de 10 anos foi de R$ 46.522,44 no grupo em monoterapia com atorvastatina versus R$ 236.141,85 na terapia combinada, com uma efetividade global de 0,54 e 0,73, respectivamente. Isso resultou em uma RCEI R$ 1.011.188,07 (R$ 864.498,95 a R$ 1.296.748,43) por desfecho cardiovascular evitado. Conclusões: Apesar de não existirem padrões nacionais para custo-efetividade, os dados encontrados sugerem que a estratégia de associação do evolocumabe à terapia com estatina não é, no momento, custo-efetiva.

Abstract Background: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

Análise dos custos de medicamentos no tratamento das dislipidemias em Ribeirão Preto, SP, Brasil / Analysis of dyslipidemia treatment drug costs in Ribeirão Preto, São Paulo State, Brasil

Fundamentos: As dislipidemias representam importante fator de risco para o desenvolvimento de doençascardiovasculares, comprovado por meio de grandes estudos observacionais.Objetivo: Analisar os custos de utilização de atorvastatina, sinvastatina, bezafibrato e ciprofibrato por indivíduospertencentes ao Programa de Medicamentos Excepcionais do Ministério da Saúde, distribuídos pelo Hospital das Clínicas de Ribeirão Preto, SP, Brasil, em 2007. Métodos: Estudo observacional, descritivo e de carátertransversal. Casuística composta por 332 (31,11%) indivíduos sorteados aleatoriamente dentre 1067 pacientes, de ambos os sexos, encaminhados pelo Sistema Único de Saúde (SUS) e consultórios particulares. Os indivíduos foram entrevistados e seus prontuáriosmédicos analisados. Resultados: Dos 312 pacientes entrevistados, 157 (51%) eram do sexo masculino. A faixa etária variou de 15-63 anos (62,0±12,23 anos). Fizeram uso de estatinas 227 (73,22%) pacientes; 54 (17,42%) de fibratos e 31 (10%)pacientes formavam o grupo-controle. O tratamento do grupo atorvastatina apresentou o maior custo (R$994,69paciente/ano), já no grupo da sinvastatina (R$337,61 paciente/ano) houve maiores gastos com exameslaboratoriais e complementares. No grupo dos fibratos, a categoria de medicamentos foi a que gerou maiorgasto em ambos os grupos. Os pacientes do grupo ciprofibrato apresentaram mais necessidade de exameslaboratoriais e complementares em relação ao grupo bezafibrato.Conclusões: O tratamento com atorvastatina foi o mais oneroso, entretanto, os pacientes apresentaram menor ocorrência de eventos e procedimentos cardiovasculares, além do menor custo com exames laboratoriais.

Eficácia da atorvastatina sem administração diária / Efficacy of atorvastatin when not administered daily

FUNDAMENTO: As estatinas têm larga utilização por reduzirem eventos cardíacos. Indicadas para uso diário, no entanto alguns a utilizam em dias alternados, principalmente visando diminuição de custos. OBJETIVO: Avaliar a eficácia da atorvastatina sem administração diária sobre os níveis de LDL-colesterol (LDL-C) e a redução dos custos. MÉTODOS: Foram avaliados 100 pacientes (P) hipercolesterolêmicos em prevenção primária (PP) e secundária (PS). Após período de dieta de 12 semanas iniciou-se atorvastatina 10 mg por dia. Após seis semanas foi dosado o LDL-C, e se níveis <80 ou <104 mg/dl conforme PS e PP, respectivamente, foi feita subtração de duas tomadas de atorvastatina da semana. Caso LDL-C continuasse <80 ou <104 mg/dl permitiria novo ajuste para três vezes na semana, sendo feita última dosagem após seis semanas. A variação porcentual de custos foi a forma de apreciar a economia. RESULTADOS: Em 47 P, dos 52 desse grupo, observou-se redução de LDL-C de 32 por cento, permanecendo com atorvastatina diária. Quarenta e um ficaram até o final do estudo e tiveram redução da posologia semanal. Em 25 P, a medicação foi administrada três vezes por semana e, em 16, cinco vezes por semana, exibindo redução de LDL-C de 42,4 por cento e 46,1 por cento, respectivamente. Sobre custos, um dos grupos teve despesa mensal de R$ 106,65 reduzido para R$ 74,65, e outro grupo, o gasto de R$ 106,65 foi reduzido a R$ 53,33. CONCLUSÃO: Os resultados sugerem que é possível administrar a atorvastatina de forma não-diária e observou-se redução dos custos entre 30 por cento e 50 por cento.

BACKGROUND: Statins are widely used because they reduce cardiac events. Although they are indicated for daily use, some doctorsgive prescriptions for every other day, mainly with the purpose of reducing costs. OBJECTIVE: To evaluate the efficacy of atorvastatin, when not administered everyday, on LDL-cholesterol (LDL-C) levels, and also to evaluate cost reduction. METHODS: A total of 100 patients with hypercholesterolemia in primary (PP) and secondary prevention (SP) were assessed. After a 12-week diet period, atorvastatin was initiated at a dose of 10 mg per day. After six weeks, LDL-C was determined, and if the levels were <80 or <104 mg/dL for SP and PP, respectively, two atorvastatin doses were subtracted per week. If LDL-C remained <80 or <104 mg/dL, a further reduction to three times a week was allowed, and the last determination was performed after six more weeks. The percentage variation in costs was the parameter to evaluate the saving. RESULTS: In 47 out of the 52 patients of this group, a reduction by 32 percent in LDL-C was observed, and daily atorvastatin was maintained. Forty one patients remained throughout the study and had their weekly dosage reduced. In 25 patients the medication was administered three times a week, and in 16, five times a week, with reductions of 42.4 percent and 46.1 percent in LDL-C, respectively. As regards costs, one of the groups had their monthly expense reduced from R$ 106.65 to R$ 74.65, and the other group from R$ 106.65 to R$ 53.33. CONCLUSION: The results suggest that atorvastatin may be administered on a non-daily basis. A cost reduction between 30 percent and 50 percent was also observed.