用塔氟他胺治疗转甲状腺素淀粉样变心肌病患者的生存和心血管相关住院频率建模。
Modeling of Survival and Frequency of Cardiovascular-Related Hospitalization in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis.
机构信息
Clinical Pharmacology, Pharmacometrics, Pfizer Inc, Cambridge, MA, USA.
Clinical Pharmacology, Pharmacometrics, Pfizer Inc, Sandwich, UK.
出版信息
Am J Cardiovasc Drugs. 2021 Sep;21(5):535-543. doi: 10.1007/s40256-021-00464-y. Epub 2021 Mar 26.
INTRODUCTION
ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) demonstrated the efficacy and safety of tafamidis in transthyretin amyloid cardiomyopathy (ATTR-CM). Model-based analyses from ATTR-ACT can examine predictor effects on dose-response/exposure-response relationships.
METHODS
Parametric hazard distributions were developed for all-cause mortality and frequency of cardiovascular-related hospitalization. Time-to-event models were fitted to survival data, and repeated time-to-event models were fitted to hospitalization data. Disease-specific characteristics were assessed as baseline predictors of event hazards.
RESULTS
There were 441 patients in this analysis. At month 30, 70.5% (tafamidis) and 57.1% (placebo) of patients were alive, with 154/441 deaths reported; 495 cardiovascular-related hospitalizations occurred. The cumulative risk of death was 42.1% (95% confidence interval [CI] 24.2-58.0) lower with tafamidis than with placebo, regardless of New York Heart Association (NYHA) class; significant predictors of decreased risk were genotype (wild-type), greater 6-Minute Walk Test (6MWT) distance, higher left ventricular ejection fraction (LVEF), and lower blood urea nitrogen (BUN) and N-terminal pro-B-type natriuretic peptide concentrations. The average cumulative risk of cardiovascular-related hospitalization up to 30 months was 40.8% (95% CI 31.0-49.7) lower with tafamidis in NYHA class I/II patients. Significant predictors of reduced risk were greater 6MWT distance, higher LVEF, and lower BUN and troponin I concentrations.
CONCLUSIONS
Tafamidis reduced cumulative mortality and hospitalization risk versus placebo in patients with ATTR-CM. Baseline predictors of outcome were consistent with the cardiovascular nature of the disease and suggested that earlier treatment may improve outcomes. CLINICAL TRIALS.
GOV IDENTIFIER
NCT01994889 (date of registration: November 26, 2013).
简介
ATTR-ACT（转甲状腺素蛋白淀粉样变心肌病临床试验）证明了塔法米迪在转甲状腺素蛋白淀粉样变心肌病（ATTR-CM）中的疗效和安全性。来自ATTR-ACT 的基于模型的分析可以检查对剂量反应/暴露反应关系的预测因子影响。
方法
为全因死亡率和心血管相关住院频率开发了参数危险分布。对生存数据进行了时间事件模型拟合，对住院数据进行了重复时间事件模型拟合。疾病特异性特征被评估为事件危险的基线预测因子。
结果
本分析共纳入 441 例患者。在第 30 个月时，70.5%（塔法米迪）和 57.1%（安慰剂）的患者存活，报告了 154/441 例死亡；发生了 495 次心血管相关住院。无论纽约心脏协会（NYHA）分级如何，塔法米迪治疗的患者死亡累积风险均降低了 42.1%（95%置信区间[CI]24.2-58.0）；降低风险的显著预测因子包括基因型（野生型）、更大的 6 分钟步行测试（6MWT）距离、更高的左心室射血分数（LVEF）以及更低的血尿素氮（BUN）和 N 末端 pro-B 型利钠肽浓度。在 NYHA 分级 I/II 患者中，在 30 个月内，塔法米迪治疗的心血管相关住院的累积风险平均降低了 40.8%（95%CI31.0-49.7）。降低风险的显著预测因子包括更大的 6MWT 距离、更高的 LVEF 以及更低的 BUN 和肌钙蛋白 I 浓度。
结论
与安慰剂相比，塔法米迪降低了 ATTR-CM 患者的累积死亡率和住院风险。结局的基线预测因子与疾病的心血管性质一致，表明早期治疗可能改善结局。临床试验。
政府标识符
NCT01994889（注册日期：2013 年 11 月 26 日）。
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