From the British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences (L.S., P.S.J., M.C.P., J.J.V.M.), and Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing (J.G.F.C.), University of Glasgow, the Department of Cardiology, Golden Jubilee National Hospital (M.C.P.), and the Cardiology Department, Glasgow Royal Infirmary (H.J.D.), Glasgow, and the National Heart and Lung Institute, Imperial College London, London (J.G.F.C.) - all in the United Kingdom; the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (B.L.C., S.D.S.); the Department of Cardiovascular Research, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan (S.B., R.L.), Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence (A.P.M.), and Maria Cecilia Hospital, Gruppo Villa Maria Care and Research, Ettore Sansavini Health Science Foundation, Cotignola (L.T.) - all in Italy; Duke Clinical Research Institute, Duke University, Durham, NC (C.B.G.); Rikshospitalet University Hospital, Oslo (J.K.); the Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen (L.K.); Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas (M.P.); the Department of Medicine, University of Michigan, Ann Arbor (B.P.); the Center for Person-Centered Care (K.S.) and Sahlgrenska Academy (J.W.), University of Gothenburg, Gothenburg, Sweden; INSERM Centre d'Investigation Clinique 1433, Université de Lorraine and Centre Hospitalier Universitaire, Nancy, France (F.Z.); and the Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston (M.R.Z.).
N Engl J Med. 2017 Jul 6;377(1):41-51. doi: 10.1056/NEJMoa1609758.
The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail.
We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization.
Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P=0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis.
Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.).
随着血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、β受体阻滞剂和盐皮质激素受体拮抗剂等药物的序贯引入，有症状的射血分数降低的心力衰竭患者的猝死风险已经发生了变化。我们试图详细研究这一趋势。
我们分析了来自 40195 名射血分数降低的心力衰竭患者的数据，这些患者参加了 12 项临床试验，这些试验的时间跨度从 1995 年到 2014 年。在试验入组时已植入植入式心脏复律除颤器的患者被排除在外。使用加权多变量回归分析随时间推移的猝死率趋势。使用 Cox 回归模型计算每个试验组猝死的调整后危险比。根据随机分组后不同时间点和心力衰竭诊断与随机分组之间的时间间隔评估猝死的累积发生率。
3583 例患者报告猝死。与未发生猝死的患者相比，这些患者年龄更大，男性更多，心力衰竭的病因是缺血性，心功能更差。试验中猝死率下降了 44%（P=0.03）。随机分组后 90 天的猝死累积发生率在最早的试验中为 2.4%，在最近的试验中为 1.0%。近期诊断心力衰竭的患者猝死率并不高于长期诊断心力衰竭的患者。
在参加临床试验的有症状的射血分数降低的心力衰竭门诊患者中，猝死率随时间显著下降，这一发现与基于证据的药物对这一死因的累积获益一致。（由中国国家留学基金委员会和格拉斯哥大学资助）。
