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Balancing Risks and Benefits of Direct Oral Anticoagulants in Older Ischemic Stroke Patients with Atrial Fibrillation

平衡老年缺血性卒中合并心房颤动患者直接口服抗凝药的风险和益处

基本信息

批准号：
10241532
负责人：
Ying Xian
金额：
$ 56.77万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10241532
关键词：
Address Adoption Age Aging American American Heart Association Anticoagulant therapy Anticoagulants Anticoagulation Atrial Fibrillation Benefits and Risks Cardiology Cardiovascular Diseases Characteristics Chemicals Clinical Clinical Trials Clinical effectiveness Community Practice Comparative Effectiveness Research Complex Creatinine Data Databases Development Dose Drug Kinetics Effectiveness Embolism Ensure Equilibrium Event Evidence based treatment Goals Guidelines Health Hemorrhage Heterogeneity Hospitals Individual Inpatients Ischemic Stroke Knowledge Lead Level of Evidence Life Link Machine Learning Medicare Methods Mission Modeling Observational Study Oral Outcome Overdose Patient risk Patients Pattern Pharmaceutical Preparations Population Practice Guidelines Prevalence Primary Prevention Probability Public Health Publications Quality of Care Race Recording of previous events Recurrence Registries Renal clearance function Renal function Research Risk Risk Factors Safety Sampling Schedule Secondary Prevention Selection Bias Selection for Treatments Seminal Severities Societies Specific qualifier value Stroke Stroke prevention Subgroup Techniques Testing Therapeutic Translations United States United States Centers for Medicare and Medicaid Services United States National Institutes of Health Warfarin Weight base burden of illness care outcomes clinical practice clinically relevant college comorbidity comparative effectiveness analysis disability effectiveness outcome ethnic minority population evidence base head-to-head comparison high risk improved improved outcome individual patient individualized medicine innovation medication compliance novel patient oriented personalized medicine preference prevent relative effectiveness risk benefit ratio safety outcomes sex shared decision making stroke outcome stroke patient stroke survivor therapy design tool treatment effect

项目摘要

The 2019 U.S. practice guidelines recommend direct oral anticoagulants (DOACs) such as dabigatran, rivarox- aban, and apixaban over warfarin for stroke prevention in high-risk patients with atrial fibrillation (AF). However, the selection of a DOAC can be challenging for older ischemic stroke patients. The risk-benefit ratios in second- ary stroke prevention differ substantially from those in primary prevention. Not only are older stroke survivors at increased risk for recurrent ischemic events, older age and history of ischemic stroke are also major risk factors for bleeding complications. While it is known that drug selection should be individualized, it remains unknown how to tailor anticoagulant therapy according to the effectiveness/safety of the agents and patient unique char- acteristics. The long-term goal is to use comparative effectiveness research to improve quality of care and out- comes in patients with cardiovascular disease and stroke. Leveraging the American Heart Association (AHA) Get With The Guidelines-Stroke Registry (GWTG-Stroke) and Medicare inpatient and Part D database, the over- all objective of this application is to develop evidence-based strategies to improve appropriate anticoagulant therapy for secondary prevention in older ischemic stroke patients with AF. The central hypothesis is that differ- ences exist between DOACs in terms of effectiveness and safety, which have direct implications for therapeutic selection. Once the relative effectiveness/safety is known, the selection of an anticoagulant can be made based on patient risk profiles, making treatment safer and more effective. Guided by strong preliminary data, this hy- pothesis will be tested by pursuing two specific aims: 1) Determine the long-term clinical effectiveness and safety of different DOACs for secondary prevention in older ischemic stroke patients with AF; 2) Investigate DOACs dosing patterns and evaluate the potential impact of underdosing or overdosing on long-term outcomes. The proposed research is innovative in four key ways: 1) A patient-centered approach is used to address a real-life decisional dilemma facing stroke survivors and clinicians; 2) It shifts focus from selected samples in clinical trials to a nationwide representative stroke population, including traditionally underrepresented subgroups in commu- nity practice; 3) A novel propensity score inverse probability weighting method using generalized boosted models (a machine learning technique) will be employed to mimic a trial-type multi-treatment design, uncover treatment heterogeneity, and minimize selection bias in observational data; 4) Beyond traditional mechanisms of scientific publications, the evidence generated from this study will be disseminated to stroke survivors, clinicians, and relevant stakeholders through the AHA GWTG-led national quality initiatives and patient-led efforts to ensure a rapid translation of seminal findings into clinical practice. The proposed research is significant because it is expected to help guide personalized anticoagulant therapy in older ischemic stroke survivors that could best meet their needs and lead to better outcomes most meaningful to patients. Ultimately, such knowledge has the potential to inform evidence-based treatment decisions in stroke that now afflicts more than 7.2 million Americans.

2019年美国实践指南推荐直接口服抗凝血剂（DOACs），如达比加群、利伐罗等