Hinda and Arthur Marcus Institute for Aging Research, , Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA.
Harvard Medical School, Boston, MA, USA.
Drugs Aging. 2024 Sep;41(9):763-773. doi: 10.1007/s40266-024-01142-9. Epub 2024 Sep 11.
Prospective sequential analyses after a new drug approval allow proactive surveillance of new drugs. In the current study, we demonstrate feasibility of frailty-specific sequential analyses for dabigatran, rivaroxaban, and apixaban versus warfarin.
We partitioned Medicare data from 2011 to 2020 into datasets based on calendar year following the date of drug approval. Each calendar year of data was added sequentially for analysis. We used a new-user, active comparative design by comparing the initiators of dabigatran versus warfarin, rivaroxaban versus warfarin, and apixaban versus warfarin. Patients aged ≥ 65 years with atrial fibrillation without contraindication to the anticoagulants were included. Claims-based frailty index ≥ 0.25 was used to define frailty. The initiators of each direct oral anticoagulant were propensity-score matched to the initiators of warfarin within each frailty status. The effectiveness outcome was ischemic stroke or systemic thromboembolism, and the safety outcome was major bleeding. For each calendar year, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards models using all data available up to that year.
As an example of the results, in the 2020 dataset, compared with warfarin, apixaban was associated with a reduced risk of ischemic stroke or systemic thromboembolism (frail: HR 0.73, 95% CI 0.63-0.85; non-frail: HR 0.65, 95% CI 0.59-0.72) and major bleeding (frail: HR 0.63, 95% CI 0.57-0.69; non-frail: HR 0.59, 95% CI 0.56-0.63) in both frail and non-frail patients. We found evidence for apixaban's effectiveness and safety within 1-2 years after the drug approval in frail older patients.
Our frailty-specific sequential analyses can be applied to future near-real-time monitoring of newly approved drugs.
新药批准后的前瞻性序贯分析可主动监测新药。本研究旨在演示达比加群、利伐沙班和阿哌沙班相对于华法林的特定虚弱性序贯分析的可行性。
我们将 2011 年至 2020 年的医疗保险数据根据药物批准日期后的日历年度划分为数据集。每年的数据都按顺序添加到分析中。我们采用新用户、主动比较设计，比较达比加群与华法林、利伐沙班与华法林和阿哌沙班与华法林的使用者。纳入年龄≥65 岁且无抗凝剂禁忌的心房颤动患者。使用基于索赔的虚弱指数≥0.25 来定义虚弱。根据每个虚弱状态，将每种直接口服抗凝剂的使用者与华法林的使用者进行倾向评分匹配。有效性结局为缺血性卒中或全身性血栓栓塞，安全性结局为大出血。对于每个日历年度，我们使用当年之前所有可用数据，从 Cox 比例风险模型中估计风险比（HR）和 95%置信区间（CI）。
作为结果的一个示例，在 2020 年数据集，与华法林相比，阿哌沙班与缺血性卒中或全身性血栓栓塞（虚弱：HR 0.73，95%CI 0.63-0.85；非虚弱：HR 0.65，95%CI 0.59-0.72）和大出血（虚弱：HR 0.63，95%CI 0.57-0.69；非虚弱：HR 0.59，95%CI 0.56-0.63）风险降低相关，虚弱和非虚弱患者均如此。我们发现，在虚弱的老年患者中，在药物批准后 1-2 年内，阿哌沙班具有有效性和安全性证据。
我们的特定虚弱性序贯分析可应用于未来对新批准药物的近乎实时监测。
