Department of Pharmacy Practice, University of Connecticut School of Pharmacy, 69 North Eagleville Road, Unit 3092, Storrs, CT, USA.
Evidence-Based Practice Center, Hartford Hospital, Hartford, CT, USA.
ESC Heart Fail. 2019 Feb;6(1):10-15. doi: 10.1002/ehf2.12365. Epub 2018 Oct 9.
Heart failure (HF) is a common co-morbidity in non-valvular atrial fibrillation (NVAF) patients and a potent risk factor for stroke, bleeding, and a decreased time-in-therapeutic range with warfarin. We assessed the real-world effectiveness and safety of rivaroxaban and warfarin in NVAF patients with co-morbid HF.
Using US Truven MarketScan Commercial and Medicare supplemental database claims data from 11/2011 to 12/2016, we identified oral anticoagulant (OAC)-naïve NVAF patients with HF (International Classification of Diseases, 10th Revision codes of I50 or I09.81) and ≥12 months of insurance coverage prior to the qualifying OAC dispensing. Rivaroxaban users (20 or 15 mg once daily) were 1:1 propensity score matched to warfarin users, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed up until an event, OAC discontinuation/switch, insurance disenrolment, or end of follow-up. Rates [events per 100 person-years (PYs) of follow-up] for stroke or systemic embolism and major bleeding (using the Cunningham algorithm) were compared between the matched cohorts using Cox proportion hazard regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). We matched 3418 rivaroxaban (32% receiving the reduced dose) and 3418 warfarin users with NVAF and HF with a median (interquartile range) available follow-up of 1.4 (0.6, 2.5) years. Median age was 74 (63, 82) years, and median CHA DS -VASc and HASBLED scores were 4 (3, 5) and 2 (2, 3). Common HF medications included beta-blockers (64%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (62%), loop diuretics (46%), digoxin (11%), and aldosterone receptor antagonists (10%). The hazard of developing stroke or systemic embolism (0.98 events/100PY vs. 1.28 events/100PY; HR = 0.82, 95% CI = 0.47-1.44), ischaemic stroke (0.70 events/100PY vs. 1.02 events/100PY; HR = 0.77, 95% CI = 0.41-1.46), or major bleeding (3.86 events/100PY vs. 4.23 events/100PY; HR = 0.98, 95% CI = 0.73-1.31) was not found to be different between rivaroxaban and warfarin users. Intracranial haemorrhage was infrequent in both cohorts and numerically less with rivaroxaban (0.27 events/100PY vs. 0.36 events/100PY; HR = 0.73, 95% CI = 0.25-2.08).
Effectiveness and safety of rivaroxaban vs. warfarin are sustained in NVAF patients with co-morbid HF treated in routine practice. The general consistency between this real-world study and those from phase III randomized trial data of rivaroxaban should provide additional reassurance to clinicians regarding the use of rivaroxaban in NVAF patients with HF.
心力衰竭（HF）是非瓣膜性心房颤动（NVAF）患者的常见合并症，也是华法林治疗中风、出血和治疗时间窗减少的有力危险因素。我们评估了利伐沙班和华法林在合并 HF 的 NVAF 患者中的真实世界疗效和安全性。
我们使用美国 Truven MarketScan 商业和 Medicare 补充数据库的索赔数据，从 2011 年 11 月至 2016 年 12 月，确定了伴有 HF（国际疾病分类，第 10 版代码为 I50 或 I09.81）和在合格 OAC 配药前有≥12 个月保险覆盖的 NVAF 患者。利伐沙班组（20 或 15mg 每日一次）与华法林组进行了 1:1 的倾向评分匹配，匹配后所有协变量的残差绝对标准化差异<0.1。患者随访至发生事件、OAC 停药/转换、保险退出或随访结束。使用 Cox 比例风险回归比较匹配队列中风或全身性栓塞和大出血（使用 Cunningham 算法）的发生率[每 100 人年（PY）随访事件率]，并报告为风险比（HR）及其 95%置信区间（CI）。我们匹配了 3418 名利伐沙班组（32%接受低剂量）和 3418 名利伐沙班组患者，NVAF 和 HF 的中位（四分位间距）随访时间为 1.4（0.6，2.5）年。中位年龄为 74（63，82）岁，中位 CHA2DS2-VASc 和 HASBLED 评分分别为 4（3，5）和 2（2，3）。常见的 HF 药物包括β受体阻滞剂（64%）、血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂（62%）、噻嗪类利尿剂（46%）、地高辛（11%）和醛固酮受体拮抗剂（10%）。发生中风或全身性栓塞（0.98 事件/100PY 与 1.28 事件/100PY；HR=0.82，95%CI=0.47-1.44）、缺血性中风（0.70 事件/100PY 与 1.02 事件/100PY；HR=0.77，95%CI=0.41-1.46）或大出血（3.86 事件/100PY 与 4.23 事件/100PY；HR=0.98，95%CI=0.73-1.31）的风险在利伐沙班组和华法林组之间未发现有差异。两组颅内出血均较少且利伐沙班组的发生率较低（0.27 事件/100PY 与 0.36 事件/100PY；HR=0.73，95%CI=0.25-2.08）。
在合并 HF 的 NVAF 患者中，利伐沙班与华法林的有效性和安全性在常规实践中是持续的。这项真实世界研究与利伐沙班 III 期随机试验数据之间的一般一致性，应能为临床医生在合并 HF 的 NVAF 患者中使用利伐沙班提供额外的信心。
