Declining stroke and vascular event recurrence rates in secondary prevention trials over the past 50 years and consequences for current trial design.
Declining stroke and vascular event recurrence rates in secondary prevention trials over the past 50 years and consequences for current trial design.
复制标题
DOI：
10.1161/circulationaha.109.934786
复制
发表时间：
2011-05-17
期刊：
影响因子：
37.8
通讯作者：
Saver JL
中科院分区：
文献类型：
--
作者：
Hong KS;Yegiaian S;Lee M;Lee J;Saver JL
人们普遍认为，但没有得到充分证明，标准护理的累积进步已经减少了二级预防试验中的复发性中风和心血管事件。系统搜索确定了 1960 年至 2009 年发表的所有医学二级卒中预防疗法的随机对照试验 (RCT)。狭隘地关注单一卒中机制的 RCT，包括心房颤动、颈动脉和颅内狭窄被排除在外。从各个试验的对照组中，我们提取了复发性中风、致命性中风和主要血管事件的基线特征和年度事件发生率的数据，并分析了随时间变化的趋势。确定了 59 项随机对照试验，纳入了 66,157 名对照组患者。在这 5 个十年期间，每十年复发性中风的年度事件发生率下降 0.996% (p=0.001)，致命性中风下降 0.282% (p=0.003)，主要血管事件下降 1.331% (p=0.001)。多元回归分析发现，增加抗血栓药物的使用和降低血压是减少中风复发的主要原因。对于复发性中风，年发病率从 1960 年代启动的试验中的 8.71% 下降到 1970 年代的 6.10%、1980 年代的 5.41%、1990 年代的 4.04%，到 2000 年代的 4.98%。在此期间，为了使试验有足够的功效来检测复发性中风减少 20%，所需的样本量增加了 2.2 倍。过去 5 年来，复发性中风和血管事件发生率大幅下降，主要原因是血压控制的改善和更频繁地使用抗血小板治疗。现在需要相当大的样本量来证明医疗二级预防的逐步改进。
It is widely supposed, but not well-demonstrated, that cumulative advances in standard care have reduced recurrent stroke and cardiovascular events in secondary prevention trials. Systematic search identified all randomized controlled trials (RCTs) of medical secondary stroke prevention therapies published from 1960 to 2009. RCTs narrowly focused on single stroke mechanisms, including atrial fibrillation, cervical carotid, and intracranial stenosis were excluded. From control arms of individual trials, we extracted data for baseline characteristics and annual event rates for recurrent stroke, fatal stroke, and major vascular events, and analyzed trends over time. 59 RCTs were identified, enrolling 66,157 patients in control arms. Over the 5 decade periods, annual event rates declined, per decade, for recurrent stroke by 0.996% (p=0.001), fatal stroke by 0.282% (p=0.003), and major vascular events by 1.331% (p=0.001). Multiple regression analyses identified increasing antithrombotics use and lower blood pressures as major contributors to the decline in recurrent stroke. For recurrent stroke, annual rates fell from 8.71% in trials launched in 1960s, through 6.10% in 1970s, 5.41% in 1980s, 4.04% in 1990s, to 4.98% in 2000s. The sample size required for a trial to have adequate power to detect a 20% reduction in recurrent stroke increased 2.2-fold during this period. Recurrent stroke and vascular event rates have declined substantially over the last 5 decades, with improved blood pressure control and more frequent use of antiplatelet therapy as the leading causes. Considerably larger sample sizes are now needed to demonstrate incremental improvements in medical secondary prevention.