Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands (M.C.S.-S., J.v.d.L., J.A.N.D., F.L.J.V.).
Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (S.J.C., J.W.E.).
Circulation. 2019 Jun 18;139(25):2846-2856. doi: 10.1161/CIRCULATIONAHA.118.035266. Epub 2019 May 3.
We aimed to estimate absolute benefit and harm from treatment with dabigatran in individual patients with atrial fibrillation, and to select the optimal dose for each individual.
We derived and validated a prediction model for ischemic stroke/systemic embolism and major bleeding in patients with atrial fibrillation from the 3 treatment arms of the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy With Dabigatran Etexilate) (n=11 955 in derivation cohort, n=6158 in validation cohort). Readily available patient characteristics were included in Fine and Gray competing risk models (sex, age, smoking, antiplatelet drugs, previous vascular disease, diabetes mellitus, blood pressure, estimated glomerular filtration rate, and hemoglobin). Five-year risks for ischemic stroke/systemic embolism and major bleeding were estimated without anticoagulation therapy, and compared with high- and low-dose dabigatran.
Model calibration was good, and discrimination was adequate with a c-statistic of 0.65 (95% CI, 0.62-0.70) for ischemic stroke/systemic embolism and 0.69 (95% CI, 0.66-0.71) for major bleeding. The 5-year absolute risk reduction for ischemic stroke/systemic embolism with dabigatran 150 mg twice daily ranged from <10% in 20% of patients to >25% in 14% of patients, and the 5-year absolute risk increase for major bleeding ranged from <5% in 53% of patients to 15% to 20% in 1% of patients. Comparing high-dose to low-dose dabigatran, the net benefit (absolute risk reduction minus absolute risk increase) was positive for 46% of patients.
The absolute treatment benefits and harms of dabigatran in atrial fibrillation can be estimated based on readily available patient characteristics. Such treatment effect estimations can be used for shared decision making before starting dabigatran treatment and to determine the optimal dose.
URL: https://www.clinicaltrials.gov . Unique identifier: NCT00262600.
我们旨在评估达比加群在房颤患者中的治疗的绝对获益和危害，并为每位患者选择最佳剂量。
我们从 RE-LY 试验（达比加群酯的随机长期抗凝治疗评估）的 3 个治疗组（推导队列中 11955 例，验证队列中 6158 例）中推导出并验证了房颤患者缺血性卒中/全身性栓塞和大出血的预测模型。纳入 Fine 和 Gray 竞争风险模型的患者特征包括（性别、年龄、吸烟、抗血小板药物、既往血管疾病、糖尿病、血压、估算肾小球滤过率和血红蛋白）。未接受抗凝治疗时，估计 5 年内缺血性卒中/全身性栓塞和大出血的风险，并与高剂量和低剂量达比加群进行比较。
模型校准良好，区分度适中，缺血性卒中/全身性栓塞的 C 统计量为 0.65（95%CI，0.62-0.70），大出血的 C 统计量为 0.69（95%CI，0.66-0.71）。达比加群 150mg 每日两次的 5 年缺血性卒中/全身性栓塞绝对风险降低范围从 20%的患者<10%到 14%的患者>25%，大出血的 5 年绝对风险增加范围从 53%的患者<5%到 1%的患者 15%至 20%。与低剂量达比加群相比，高剂量达比加群对 46%的患者具有净获益（绝对风险降低减去绝对风险增加）。
基于可获得的患者特征，可以评估达比加群在房颤中的绝对治疗获益和危害。这种治疗效果估计可用于开始达比加群治疗前的共同决策，并确定最佳剂量。
