ESC 2020丨真实世界和临床试验双重验证，艾多沙班是老年房颤患者安全有效的抗凝选择

图1. 亚洲二级预防真实世界研究结果

Lip教授表示，真实世界证据是对RCT结果的重要补充，拓展了试验数据的普遍性。来自亚洲的多项真实世界数据一致明确证实了艾多沙班在亚洲房颤患者（尤其是老年等高危患者）中的有效性和安全性优于华法林，有力支持了RCT研究的结果。

Joris de Groot教授：最新ETNA-AF注册研究结果力证艾多沙班真实世界获益

ENTA-AF Europe注册研究 [7] 评估了艾多沙班在欧洲、东亚和日本NVAF患者常规临床实践中应用的获益和风险。基线时，与ENGAGE AF-TIMI 48非亚洲队列相比，ENTA-AF Europe研究患者年龄略大、CHA ₂DS ₂-VASc评分略低而HAS-BLED评分略高。有至少一种以下因素者被视为高危患者：既往卒中史、既往大出血史、既往ICH史或CHA ₂DS ₂-VASc评分≥4分。基线CrCl≤50 ml/min的患者比例分别为：艾多沙班60 mg组8.3%，30 mg组60.2%。基线高危患者比例分别为艾多沙班60 mg组32.1%，30 mg组58.9%，高危患者占整体人群的38.4%。

随访1年结果显示，ENTA-AF Europe研究整体人群首次发生卒中/SEE（0.82%）和出血性卒中发生率（0.11%）均很低，艾多沙班两个剂量组与整体人群相似，数值均低于ENGAGE AF-TIMI 48非亚洲队列（图2）。出血方面，无论艾多沙班剂量如何，颅内出血发生率均低，大出血发生率明显低于ENGAGE AF-TIMI 48非亚洲队列（图3）。艾多沙班所有年龄亚组的大出血和缺血性卒中发生率普遍低，大出血事件中颅内出血的比例相似。全因死亡率随年龄增加而增加，但并非心血管原因所驱动。该结果支持了艾多沙班在常规临床实践中用于老年（包括≥85岁）房颤患者中的安全性和有效性 [8] 。

图2. 真实世界艾多沙班治疗下卒中/SEE的发生率低于ENGAGE非亚洲队列

图3. 真实世界艾多沙班治疗下大出血发生率低于ENGAGE非亚洲队列

Groot教授最后指出，欧洲常规临床实践在接受艾多沙班治疗的超过1,3000例未经选择且大部分为老年的房颤患者中，观察到大出血和卒中/SEE的低发生率，强调了艾多沙班的有效性和安全性，证实了随机试验报告的结果。艾多沙班真实世界中ICH和出血性卒中发生率一致保持在低水平且独立于年龄或艾多沙班剂量的结果令人振奋。

Jan Steffel教授：老年房颤患者抗凝管理优化

Caldeira等 [9] 针对老年房颤患者开展的NOAC荟萃分析显示，老年（≥75岁）患者与较年轻（＜75岁）患者相比，NOAC相对华法林可带来更大的卒中/SEE风险降低（分别为30%和13%），获益更多。降低大出血风险方面，在＜75岁的患者中，NOAC显著优于VKA（23%）；而在≥75岁的患者中，NOAC与VKA未见显著差异，这与异质性相关，主要源于RE-LY研究和ROCKET AF研究的中性结果；而艾多沙班和阿哌沙班显著降低老年患者的大出血风险。ENGAGE AF-TIMI 48研究按年龄分层发现，艾多沙班60/30 mg相对华法林在卒中/SEE、缺血性卒中、大出血和ICH等方面各年龄组结果一致，且老年患者在净临床终点（卒中/SEE、大出血、全因死亡）获益上更有优势，绝对风险降低更显著（图4） [10] 。

图4. 老年患者艾多沙班治疗的净临床获益更显著

另一个在老年房颤患者中值得关注的问题是跌倒，跌倒显著增加出血风险。而ENGAGE AF TIMI-48研究亚组分析证实，无论是否有跌倒风险，艾多沙班均降低出血性卒中、ICH、危及生命出血、全因死亡、净临床结局的绝对风险；且在伴跌倒风险的房颤患者中，艾多沙班绝对风险降低更多（如出血性卒中、颅内出血、危及生命出血等），获益更明显（图5） [11] 。另外，ENGAGE AF TIMI-48研究根据伴随疾病负担采用更新Charlson合并症指数（CCI）对患者进行分层发现，虽然CCI评分升高与预后更差相关，但艾多沙班相对华法林的有效性、安全性和净临床结果独立于合并症存在的程度 [12] 。

图5. 艾多沙班治疗一致获益，有跌倒风险者获益更多

Steffel教授最后强调，NOAC已经成为2020卒中预防的标准治疗，艾多沙班具有优秀的安全性和有效性，在高危患者中的获益也得到明确证实，老年患者甚至较年轻患者从艾多沙班治疗中获益更多。

小结：艾多沙班有效性和安全性获临床试验和真实世界双重验证

抗凝治疗是房颤患者预防血栓栓塞事件的核心措施，考量预防缺血性事件的获益和抗凝治疗的出血风险是每个患者都要考虑的问题，尤其是对栓塞风险和出血风险均升高的老年患者来说，这一点更为重要。NOAC的出现为老年房颤患者管理开启了一道曙光，临床试验和真实世界数据一致证实，艾多沙班使亚洲患者获益更多，有效性和安全性均优于华法林，且获益在各年龄组一致存在，老年患者还可实现更大的临床净获益，因此是值得我国房颤患者尤其是老年房颤患者优选的抗凝药物。

参考文献

1. Hughey AB, Gu X, Haymart B, et al. Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials. J Thromb Thrombolysis. 2018;46(3):316-324.

3. Chan YH, Lee HF, See LC, et al. Effectiveness and Safety of Four Direct Oral Anticoagulants in Asian Patients With Nonvalvular Atrial Fibrillation. Chest. 2019;156(3):529-543.

4. Park J, Lee SR, Choi EK, et al. Effectiveness and Safety of Direct Oral Anticoagulant for Secondary Prevention in Asians with Atrial Fibrillation. J Clin Med. 2019;8(12):2228.

5. Lee SR, Choi EK, Han KD, Jung JH, Oh S, Lip GYH. Edoxaban in Asian Patients With Atrial Fibrillation: Effectiveness and Safety. J Am Coll Cardiol. 2018;72(8):838-853.

6. Chan YH, Lee HF, Chao TF, et al. Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis. Cardiovasc Drugs Ther. 2019;33(6):701-710.

7. De Groot JR, Weiss TW, Kelly P, et al. Edoxaban for stroke prevention in atrial fibrillation in routine clinical care: One year follow up of the prospective observational ETNA-AF-Europe study [published online ahead of print, 2020 Aug 13]. Eur Heart J Cardiovasc Pharmacother. 2020;pvaa079.

8. Takeshi Yamashita. et al. Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program. ESC 2020 annual meeting.

9. Caldeira D, et al. Non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis. Arch Gerontol Geriatr. 2019;81:209-214. (Corrigendum).

10. Kato ET, Giugliano RP, Ruff CT, et al. Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 2016;5(5):e003432.

11. Steffel J, Giugliano RP, Braunwald E, et al. Edoxaban Versus Warfarin in Atrial Fibrillation Patients at Risk of Falling: ENGAGE AF-TIMI 48 Analysis [published correction appears in J Am Coll Cardiol. 2017 Jul 25;70(4):512-513]. J Am Coll Cardiol. 2016;68(11):1169-1178.

12. André M Nicolau, et al. Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 tria. Eur Heart J Cardiovasc pharmacother. 2020;6:167-75.

参考文献

1. Hughey AB, Gu X, Haymart B, et al. Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials. J Thromb Thrombolysis. 2018;46(3):316-324.

3. Chan YH, Lee HF, See LC, et al. Effectiveness and Safety of Four Direct Oral Anticoagulants in Asian Patients With Nonvalvular Atrial Fibrillation. Chest. 2019;156(3):529-543.

4. Park J, Lee SR, Choi EK, et al. Effectiveness and Safety of Direct Oral Anticoagulant for Secondary Prevention in Asians with Atrial Fibrillation. J Clin Med. 2019;8(12):2228.

5. Lee SR, Choi EK, Han KD, Jung JH, Oh S, Lip GYH. Edoxaban in Asian Patients With Atrial Fibrillation: Effectiveness and Safety. J Am Coll Cardiol. 2018;72(8):838-853.

6. Chan YH, Lee HF, Chao TF, et al. Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis. Cardiovasc Drugs Ther. 2019;33(6):701-710.

7. De Groot JR, Weiss TW, Kelly P, et al. Edoxaban for stroke prevention in atrial fibrillation in routine clinical care: One year follow up of the prospective observational ETNA-AF-Europe study [published online ahead of print, 2020 Aug 13]. Eur Heart J Cardiovasc Pharmacother. 2020;pvaa079.

8. Takeshi Yamashita. et al. Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program. ESC 2020 annual meeting.

9. Caldeira D, et al. Non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis. Arch Gerontol Geriatr. 2019;81:209-214. (Corrigendum).

10. Kato ET, Giugliano RP, Ruff CT, et al. Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 2016;5(5):e003432.

11. Steffel J, Giugliano RP, Braunwald E, et al. Edoxaban Versus Warfarin in Atrial Fibrillation Patients at Risk of Falling: ENGAGE AF-TIMI 48 Analysis [published correction appears in J Am Coll Cardiol. 2017 Jul 25;70(4):512-513]. J Am Coll Cardiol. 2016;68(11):1169-1178.

12. André M Nicolau, et al. Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 tria. Eur Heart J Cardiovasc pharmacother. 2020;6:167-75.

POCKETESC2020

Immediately 返回搜狐，查看更多