Background:The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial–Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known.Methods:These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA₂DS₂-VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA₂DS₂-VA score).Results:EAST-AFNET4 randomized 1093 patients with CHA₂DS₂-VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA₂DS₂-VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA₂DS₂-VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51–0.81]; P < 0.001) but not in patients with CHA₂DS₂-VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73–1.19]; P=0.56, P_interaction=0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA₂DS₂-VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P=0.175), but occurred more often in patients with CHA₂DS₂-VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05–1.82]; P=0.019, P_interaction=0.008). Life-threatening events or death were not different between groups (CHA₂DS₂-VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA₂DS₂-VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA₂DS₂-VA score), the P_interaction was not significant for the primary efficacy outcome (P=0.25), but remained significant (P=0.044) for the primary safety outcome.Conclusions:Patients with recently diagnosed atrial fibrillation and CHA₂DS₂-VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01288352. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20. URL: https://www.isrctn.com/; Unique identifier: ISRCTN04708680.

中文翻译：

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心房颤动和高并发症负担患者的早期节律控制

背景：随机 EAST-AFNET4（心房颤动早期治疗预防卒中试验-心房颤动网络）表明，早期节律控制 (ERC) 可减少近期诊断为心房颤动和卒中危险因素的患者的不良心血管结局。ERC 在患有多种心血管合并症的患者中的有效性和安全性尚不清楚。方法：这些预先指定的 EAST-AFNET4 子分析比较了 ERC 与常规护理 (UC) 分层到更高 (CHA ₂ DS ₂ -VASc ) 患者中的有效性和安全性。评分≥4）和较低的合并症负担。敏感性分析忽略了性别（CHA ₂ DS _{2 -VA 评分）。结果：EAST-AFNET4 随机分配了 1093 名 CHA 2}患者DS ₂ -VASc 评分≥4（74.8±6.8 岁，61% 女性）和 1696 CHA ₂ DS ₂ -VASc 评分 <4（67.4±8.0 岁，37% 女性）。_{在 CHA 2} DS ₂ -VASc 评分≥4的患者中，ERC 降低了心血管死亡、卒中或因心力衰竭恶化或急性冠脉综合征住院的复合主要疗效结局（ERC，127/549 名发生事件的患者；UC，183 /544 名患者发生事件；风险比 [HR]，0.64 [0.51–0.81]；P < 0.001）但在 CHA ₂ DS ₂ -VASc 评分 <4 的患者中没有（ERC，122/846 名发生事件的患者；UC，133 /850 名患者发生事件；HR，0.93 [0.73–1.19]；P = 0.56，P_交互作用= 0.037）。在 CHA ₂ DS ₂ -VASc 评分≥4 的患者（ERC，112/549 名患者发生事件；UC，132/ 544 名患者发生事件；HR，0.84 [0.65, 1.08]；P = 0.175），但更常见于随机分配至 ERC 的 CHA ₂ DS ₂ -VASc 评分 <4 的患者（ERC，119/846 名发生事件的患者；UC， 91/850 名患者发生事件；HR，1.39 [1.05–1.82]；P = 0.019，P_交互作用= 0.008）。组间危及生命的事件或死亡没有差异（CHA ₂ DS ₂-VASc评分≥4，ERC，84/549例患者发生事件，UC，96/544例患者发生事件；CHA ₂ DS ₂ -VASc 评分 <4，ERC，75/846 名患者发生事件，UC，73/850 名患者发生事件）。当女性被忽略以创建较高和较低风险组（CHA ₂ DS ₂ -VA 评分）时，P_交互作用对于主要疗效结果不显着（P = 0.25），但对于主要疗效结果（ P = 0.044）仍然显着（P = 0.044）主要安全性结果。结论：最近诊断为心房颤动和 CHA ₂ DS _2的患者- VASc 评分≥4 应考虑 ERC 以降低心血管结局，而合并症较少的患者使用 ERC.Registration:URL: https://www.clinicaltrials.gov 的结局可能较差；唯一标识符：NCT01288352。网址：https://www.clinicaltrialsregister.eu；唯一标识符：2010-021258-20。网址：https://www.isrctn.com/；唯一标识符：ISRCTN04708680。