1、Update of secondary stroke preventionIntroduction Secondary prevention：preventing a stroke after a transient ischaemic attack(TIA)or a recurrent stroke after a first stroke.卒中二级预防概念：在发生TIA或初次中风后预防中风发生或再次发生。8 to 15%stroke or TIA patients suffer a recurrent stroke in the first year.The recurrence risk
2、 is highest in the first few weeks and declines over time.有815%的中风或TIA患者会在第一年内再次中风或发生中风。且风险在最初的几周是最高的，随时间的延长而下降。So,Immediate evaluation of patients with a stroke or TIA,identification of the pathophysiology and initiation of secondary prevention are of great importance 因此，发生TIA或中风后立即进行评估，了解其病理生理学情况积
3、极启动二级预防措施是非常重要的。Hypertension 1.HOPE:A meta-analysis comprised seven studies in 15 527 patients with TIA,ischaemic or haemorrhagic stroke.荟萃分析7项研究涉及15527个TIA、缺血性或出血性中风患者。Followed up period:25 y.随访周期：25年 Result:(1)Treatment with antihypertensives reduced the risk of stroke by 24%,risk of non-fatal str
4、oke by 21%,risk of myocardial infarction(MI)by 21%and the risk of all vascular events by 21%.服用控制高血压药物的卒中复发风险降低了24%,非致死性的卒中风险降低了21%,心肌梗塞风险降低了21%，所有的血管性事件降低了 21%。(2)the combination of an ACEI with a diuretic was more effective(45%risk reduction)than a diuretic as monotherapy(32%),monotherapy with an
5、ACEI(7%)or a beta-blocker(7%).ACEI与利尿剂联用更有效，优于利尿剂、ACEI、受体阻滞剂各自单用。2.PROGRESS：the first large-scale trial specifically performed in patients after stroke.第一个针对中风后病人实施的大型临床试验。Method:A total of 6105 patients were treated with perindopril as monotherapy or in combination with indapamide or placebo.6105例中
6、风后病人或培哚普利单用或与吲哒帕胺、安慰剂联用 Followed up period:4 y.随访周期：4年 Result:1)The absolute risk reduction for recurrent stroke was 4%,and the relative risk reduction(RRR)was 28%.卒中复发的绝对危险度下降了4%，相对危险度下降了28%.2)Monotherapy with the ACE inhibitor was not only superior to placebo but also did not achieve the same leve
7、l of blood pressure lowering than the combination therapy.The RRR for combination therapy was 43%.单用ACEI类不仅二级预防效果优于安慰剂组，且与联用相比不致于使血压降得过低。联用降低中风复发的相对危险度较高：43%.3.MOSES:Method:1352 patients with hypertension who had suffered a stroke in the last 24 months were treated either with eprosartan依普罗沙坦(600 mg
8、)or with nitrendipin(10 mg).1352例在24个月内发生过中风的高血压病人或用依普罗沙坦(600 mg)治疗或用尼群地平（10mg）治疗。Result:1)For an identical drop in blood pressure,eprosartan was superior to nitrendipin to prevent recurrent vascular events(21%RRR).具有基本相同的降压效果，但在防止血管事件复发方面依普罗沙坦 优于尼群地平治疗。2)The optimal systolic blood pressure in the M
9、OSES trial was 120140 mmHg.MOSES的研究提示中风后最佳收缩压应控制在120-140mmHg。4.PRoFESS:Method:randomized 20 332 patients with a recent ischaemic stroke to receive telmisartan替米沙坦 at 80 mg/day or placebo.随机将新近发生过中风的20332名病人分为替米沙坦80mg/d和安慰剂组。Followed up period:2.4 years.随访周期：2.4年。Result:The mean blood pressure over t
10、he trial period was lower in the telmisartan group by 3.8/2.0 mmHg.Recurrent strokes occurred in 8.7%in the telmisartan group compared to 9.2%in the placebo group,which was not significant.在试验期间替米沙坦组血压比安慰剂组平均低3.8/2.0 mmHg.其中风复发率为8.7%，安慰剂组中风复发率为 9.2%，两组间没有显著性差异。Conclusion:initiation of telmisartan ea
11、rly after a stroke,did not significantly lower the rate of recurrent strokes,other major vascular events or new diabetes。中风后早期服用替米沙坦并不能显著的阻止中风复发，及其他血管事件和新法糖尿病。High cholesterol1.Heart Protection Study(HPS)Total 20 536 high-risk patients,3280 patients had TIA or stroke and 1820 of them without concomi
12、tant CHD.共20536高危病人，其中3280具有TIA或卒中病史，1820没有伴随心脏疾病。The RRR achieved by simvastatin given for 5 years for vascular events was 20%and the absolute risk reduction 5.1%.给予辛伐他汀组（连续5年）血管事件相对危险度下降了20%，绝对危险度下降了5.1%.2.SPARCL(Stroke Prevention by Aggressive Reduction in Cholesterol Levels)Method:4731 patients
13、with TIA or stroke without CHD and LDLcholesterol levels between 100 and 190 mg/dl.The patients received either 80mg atorvastatin or placebo.4731个具有TIA或中风病史排除心脏病且LDL在100190 mg/dl被分为80mg阿托伐他汀组和安慰剂组.Followed up period:average of 4.9 y.Result:the primary endpoint(stroke)was reduced by 16%relative and 2
14、.2%absolute.第一终点事件卒中发生率下降的相对值和绝对值分别为16%和2.2%HPS VS SPARCL The rate of ischaemic stroke was reduced(218 versus 274)whereas haemorrhagic strokes were more frequent with atorvastatin(55 versus 33).这两个临床试验相比，阿托伐他汀组的卒中发生下降了相对要高一点，但发生出血性卒中的数目确相对多一点。Therapy with a statin should be initiated early after an
15、ischaemic stroke or TIA.The sudden discontinuation of a statin in patients with a stroke or acute coronary syndrome might be associated with higher morbidity and mortality.Discontinuation of statin treatment in stroke patients.Stroke 2006 在初发中风后对 具有血脂异常者应尽早开始服用他汀类调脂。具有中风或冠心病的患者突然停用他汀类会出现比较高的复发率和致死率。
16、Diabetes mellitus Randomized controlled studies were unable to show an effect of glitazones 列酮类 on vascular events in stroke patients with diabetes mellitusEffects of pioglitazoneGlitazonesin patients with type 2 diabetes with or without previous stroke:results from PROACTIVE.Stroke 2007;38 一随机对照研究未
17、能发现服用列酮类降糖药能明显降低具有糖尿病的中风患者的血管事件的发生率。Aggressive lowering of blood glucose does not reduce the risk of stroke and might even increase mortality.Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N Engl J Med 2008;358 过分降糖不但不会降低卒中的风险反而会增加恶性事件。Supplementation of vitam
18、ins The VISP study was unable to show a benefit of the treatment of high homocysteine in stroke patients with B vitamins and folic acid.VISP的研究表明具有高同型半胱氨酸的中风患者服用维生素B和叶酸未能额外获益。The HOPE-2 study also failed to demonstrate benefit.The Heart Outcomes Prevention Evaluation(HOPE)2 Investigators.Homocystein
19、e lowering with folic acid and B vitamins in vascular disease.N Engl J Med 2006;354 HOPE-2研究也得出与VISP基本相同的结论。Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease:a randomized trial.JAMA 2008;299:20272036叶酸和维生素B在具有
20、高风险心血管疾病女性受试者中对心血管事件和总致死率的效果 included 5522 patients aged 55 years and a vascular event or diabetes mellitus 包含5522例具有血管事件或糖尿病年龄大于55岁的女性受试者 treated them for 5 years with either placebo or 2.5 mg folic acid,50 mg vitamin B6 and 1 mg vitamin B12.对照组服用安慰剂，治疗组服用2.5 mg 叶酸,50 mg 维生素 B6 and 1 mg 维生素 B12.res
21、ulted in a significant reduction in homocysteine levels but not in vascular events.结果：同型半胱氨酸水平下降但血管事件未明显下降。Hormone replacement therapy after menopause 关于女性中风患者的一项随机安慰剂对照研究提示，绝经后采取激素替代疗法疗法会增加中风的死亡率，并给非致死性卒中带来较差的预后。Antiplatelet therapy 1.The MATCH study:Object:high-risk patients with TIA or ischaemic
22、stroke Aim:clopidogrel 75 mg+ASA 75 mg PK clopidogrel 75 Result:combination therapy failed to show superiority on endpoint vascular event.联合用药组未能体现在降低血管性终点事件中的优势。反而出血性并发症的发生率较高。Reversely resulted in a significant increase in bleeding complications.-not recommended.2.CHARISMA(Clopidogrel for High Ath
23、erothromboticRisk and Ischemic Stabilization,Management and Avoidance)a trial combined primary and secondary prevention Aim:clopidogrel+ASA PK ASA Result:Combination therapy failed to show a benefit and displayed a higher bleeding rate.联合用药治疗未能明显获益。出血性并发症的发生率较高。Symptomatic patients showed a trend to
24、wards a benefit for combination antiplatelet therapy.但在症状性中风患者表现出一定的优势。3.ESPS2(the second European stroke prevention study)Method:6602 patients with TIA or stroke were randomized to ASA(25 mg bid),ER-DP(200 mg bid),ASA+ER-DP or placebo.6602例TIA或中风病人随机分为ASA组，ER-DP组、二者联用组及安慰剂组。Result:For the primary e
25、ndpoint stroke,ASA+ER-DP was superior to ASA and placebo 对第一终点事件卒中来说，联用效优。ASA lowered the risk of stroke by 18%and dipyridamole monotherapy by 16%.Bleeding complications were seen more frequently with ASA and the ASA+ER-DP,DP had a similar bleeding rate as placebo ASA及联用组出血性并发症较高，DP较低。4.A head-to he
26、ad comparison of clopidogrel with ASA+ER-DP(performed in the PRoFESS study)Method:Randomized 20 332 patients with ischaemic stroke and followed for a mean period of 2.4 y.Result:There was no difference in efficacy across all endpoints and various subgroups of patients.在所有终点事件的发生发面两者之间没有明显差异。ASA+ER-D
27、P resulted in more intracranial bleedings and a higher drop out rate due to headache compared with clopidogrel(5.9%versus 0.9%).与clopidogrel 相比ASA+ER-DP的颅内出血率和因于头疼的 脱落率较高。1.European Atrial Fibrillation trial (randomized placebo-controlled trial)Numbers needed to treat(NNT)are 12/year.Result:warfarin
28、:RRR 68%V 300 mg ASA:RRR 19%2.The ACTIVE study Method:Randomized patients with AF into ASA+clopidogrel and warfarin groups.将受试的具有房颤卒中病人随机分为ASA+clopidogrel和华法令组 Result:terminated prematurely due to a significant reduction of stroke and systemic embolism in favour of warfarin.由于华法令在降低中风发生和系统性栓塞方面表现出明显
29、的显著性差异而提前终止。rate of bleeding complications was not different between the two regimens.在出血性并发症方面两者无明显差异。Prospective cohort studies have shown that treatment with aspirin or warfarin reduces the risk of recurrent stroke in the average patient with PFO to the same risk as in patients without PFO.一项前瞻性队
30、列研究显示：阿司匹林或华法令可将具有PFO的病人中风复发的危险性降至非PFO病人同等水平。Suggest:Aspirin was as effective as anticoagulation and therefore should be given 建议：在防止PFO病人中风复方方面阿司匹林具有与抗凝剂同等效果，PFO病人应该服用。1.ESPIRIT(The Stroke Prevention in Reversible Ischemia trial)Aim:studied oral anticoagulation with an INR between3.0 and 4.5 versus
31、 ASA 30 mg in patients with TIA or minor stroke without cardiac source of embolism.研究在非心源性栓塞的TIA和中风病人中，比较将INR控制在34.5的情况下服用抗凝剂和服用阿司匹林30mg的效果优劣。Result:terminated due to a significantly increased bleeding risk with anticoagulation.因抗凝剂明显增加出血性风险而中止。、lower rate of ischaemic events with anticoagulation co
32、unterbalanced by an increased risk of intracranial bleedings.抗凝剂降低缺血性卒中时间的比率被其增加率内出血的风险所抵消。2.WARSS(The Warfarin Aspirin Recurrent Stroke Study)showed a similar rate of ischaemic events and bleeding complications:warfarin(INR 1.42.8)VS ASA (in stroke patients without cardiac source of embolism)在非心源性栓
33、塞的卒中病人中华法令（INR 1.42.8）与阿司匹林的卒中再发及出血并发症事件方面大致相似。NASCET and ESC(Two large randomized trials)Result:clear benefit of carotid surgery than medical treatment in patients with high-degree stenosis.在颈动脉高度狭窄的病人中，血管内膜切除术明显优于单纯药物治疗。Taken together,the trials found an absolute risk reduction of 13.5%over 5 year
34、s for the combined endpoint of stroke and death in favour of carotid endarterectomy.总体而言，在5年随访期内，颈动脉血管内膜切除术在降低卒中及死亡等终点事件方面的绝对危险性下降13.5%，具有一定优势。The risk reduction is even higher in stenosis 90%.当颈动脉狭窄程度90%时手术可将风险降得更低。Patients with 50%ICA stenosis do not benefit from carotid endarterectomy.当颈内动脉狭窄程度70%and 8.4%for 5069%stenosis.ASA should be given prior to,during and after carotid surgery.颈动脉狭窄程度70%和狭窄程度在5069%者手术后短期内复发和死亡的风险分别是6.2%和8.4%。阿司匹林在手术前后及手术期间都应给服。
