中風二級預防更新課件

1、 Secondary prevention ： preventing a stroke after a transient ischaemic attack (TIA) or a recurrent stroke after a first stroke. 卒中二級預防概念：在發(fā)生TIA或初次中風后預防中風發(fā)生或再次發(fā)生。 8 to 15% stroke or TIA patients suffer a recurrent stroke in the first year. The recurrence risk is highest in the first few weeks and de

2、clines over time. 有815%的中風或TIA患者會在第一年內再次中風或發(fā)生中風。且風險在最初的幾周是最高的，隨時間的延長而下降。 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，發(fā)生TIA或中風后立即進行評估，了解其病理生理學情況積極啟動二級預防措施是非常重要的。 1.HOPE : A meta-analy

3、sis comprised seven studies in 15 527 patients with TIA, ischaemic or haemorrhagic stroke. 薈萃分析7項研究涉及15527個TIA、缺血性或出血性中風患者。 Followed up period: 25 y. 隨訪周期：25年 Result: (1)Treatment with antihypertensives reduced the risk of stroke by 24%,risk of non-fatal stroke by 21%, risk of myocardial infarction

4、(MI) by 21% and the risk of all vascular events by 21%. 服用控制高血壓藥物的卒中復發(fā)風險降低了24%, 非致死性的卒中風險降低了21%, 心肌梗塞風險降低了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 ACEI(7%) or a beta-blocker (

5、7%). ACEI與利尿劑聯(lián)用更有效，優(yōu)于利尿劑、ACEI、受體阻滯劑各自單用。 2.PROGRESS ： the first large-scale trial specifically performed in patients after stroke. 第一個針對中風后病人實施的大型臨床試驗。 Method :A total of 6105 patients were treated with perindopril as monotherapy or in combination with indapamide or placebo. 6105例中風后病人或培哚普利單用或與吲噠帕胺、

6、安慰劑聯(lián)用 Followed up period: 4 y. 隨訪周期：4年 Result: 1)The absolute risk reduction for recurrent stroke was 4%, and the relative risk reduction (RRR) was 28%. 卒中復發(fā)的絕對危險度下降了4%，相對危險度下降了28%. 2)Monotherapy with the ACE inhibitor was not only superior to placebo but also did not achieve the same level of blood

7、 pressure lowering than the combination therapy. The RRR for combination therapy was 43% . 單用ACEI類不僅二級預防效果優(yōu)于安慰劑組，且與聯(lián)用相比不致于使血壓降得過低。 聯(lián)用降低中風復發(fā)的相對危險度較高：43% . 3.MOSES : Method :1352 patients with hypertension who had suffered a stroke in the last 24 months were treated either with eprosartan依普羅沙坦 (600 mg

8、) or with nitrendipin (10 mg) . 1352例在24個月內發(fā)生過中風的高血壓病人或用依普羅沙坦 (600 mg) 治療或用尼群地平（10mg）治療。 Result: 1)For an identical drop in blood pressure, eprosartan was superior to nitrendipin to prevent recurrent vascular events (21% RRR). 具有基本相同的降壓效果，但在防止血管事件復發(fā)方面依普羅沙坦 優(yōu)于尼群地平治療。 2)The optimal systolic blood pres

9、sure in the MOSES trial was 120140 mmHg. MOSES的研究提示中風后最佳收縮壓應控制在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. 隨機將新近發(fā)生過中風的20332名病人分為替米沙坦80mg/d和安慰劑組。 Followed up period: 2.4 years. 隨訪周期：2.4年。 Result: The me

10、an blood pressure over the 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. 在試驗期間替米沙坦組血壓比安慰劑組平均低3.8/2.0 mmHg.其中風復發(fā)率為8.7% ，安慰劑組中風復發(fā)率為 9.2%，兩組間沒有顯著性差異。 Conclusio

11、n: initiation of telmisartan early after a stroke, did not significantly lower the rate of recurrent strokes, other major vascular events or new diabetes。 中風后早期服用替米沙坦并不能顯著的阻止中風復發(fā)，及其他血管事件和新法糖尿病。1.Heart Protection Study (HPS) Total 20 536 high-risk patients, 3280 patients had TIA or stroke and 1820 of

12、 them without concomitant CHD. 共20536高危病人，其中3280具有TIA或卒中病史，1820沒有伴隨心臟疾病。 The RRR achieved by simvastatin given for 5 years for vascular events was 20% and the absolute risk reduction 5.1% . 給予辛伐他汀組（連續(xù)5年）血管事件相對危險度下降了20% ，絕對危險度下降了5.1% . 2.SPARCL (Stroke Prevention by Aggressive Reduction in Cholestero

13、l Levels ) Method : 4731 patients with TIA or stroke without CHD and LDLcholesterol levels between 100 and 190 mg/dl. The patients received either 80mg atorvastatin or placebo. 4731個具有TIA或中風病史排除心臟病且LDL在100190 mg/dl被分為80mg阿托伐他汀組和安慰劑組. Followed up period :average of 4.9 y. Result: the primary endpoint

14、 (stroke) was reduced by 16% relative and 2.2% absolute . 第一終點事件卒中發(fā)生率下降的相對值和絕對值分別為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). 這兩個臨床試驗相比，阿托伐他汀組的卒中發(fā)生下降了相對要高一點，但發(fā)生出血性卒中的數目確相對多一點。 Ther

15、apy with a statin should be initiated early after an 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 在初發(fā)中風

16、后對 具有血脂異常者應盡早開始服用他汀類調脂。具有中風或冠心病的患者突然停用他汀類會出現比較高的復發(fā)率和致死率。 Randomized controlled studies were unable to show an effect of glitazones 列酮類 on vascular events in stroke patients with diabetes mellitusEffects of pioglitazoneGlitazonesin patients with type 2 diabetes with or without previous stroke: result

17、s from PROACTIVE . Stroke 2007; 38 一隨機對照研究未能發(fā)現服用列酮類降糖藥能明顯降低具有糖尿病的中風患者的血管事件的發(fā)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 過分降

18、糖不但不會降低卒中的風險反而會增加惡性事件。 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風患者服用維生素B和葉酸未能額外獲益。 The HOPE-2 study also failed to demonstrate benefit. The Heart Outcomes Prevention Evaluation (HOPE) 2

19、Investigators.Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354 HOPE-2研究也得出與VISP基本相同的結論。 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齡大于55歲的女性受試者 treated them for 5 years with either placebo or 2.5 mg

20、 folic acid, 50 mg vitamin B6 and 1 mg vitamin B12. 對照組服用安慰劑，治療組服用2.5 mg 葉酸, 50 mg 維生素 B6 and 1 mg 維生素 B12. resulted in a significant reduction in homocysteine levels but not in vascular events. 結果：同型半胱氨酸水平下降但血管事件未明顯下降。 關于女性中風患者的一項隨機安慰劑對照研究提示，絕經后采取激素替代療法療法會增加中風的死亡率，并給非致死性卒中帶來較差的預后。 1.The MATCH study

21、 : Object: high-risk patients with TIA or ischaemic stroke Aim: clopidogrel 75 mg + ASA 75 mg PK clopidogrel 75 Result:combination therapy failed to show superiority on endpoint vascular event. 聯(lián)合用藥組未能體現在降低血管性終點事件中的優(yōu)勢。反而出血性并發(fā)癥的發(fā)生率較高。 Reversely resulted in a significant increase in bleeding complicat

22、ions. -not recommended. 2.CHARISMA (Clopidogrel for High AtherothromboticRisk 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

23、. 聯(lián)合用藥治療未能明顯獲益。出血性并發(fā)癥的發(fā)生率較高。 Symptomatic patients showed a trend towards a benefit for combination antiplatelet therapy . 但在癥狀性中風患者表現出一定的優(yōu)勢。 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-

24、DP or placebo. 6602例TIA或中風病人隨機分為ASA組， ER-DP組、二者聯(lián)用組及安慰劑組。 Result:For the primary endpoint stroke, ASA + ER-DP was superior to ASA and placebo 對第一終點事件卒中來說，聯(lián)用效優(yōu)。 ASA lowered the risk of stroke by 18% and dipyridamole monotherapy by 16%. Bleeding complications were seen more frequently with ASA and the

25、ASA + ER-DP,DP had a similar bleeding rate as placebo ASA及聯(lián)用組出血性并發(fā)癥較高， DP較低。 4.A head-to head 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

26、in efficacy across all endpoints and various subgroups of patients. 在所有終點事件的發(fā)生發(fā)面兩者之間沒有明顯差異。 ASA +ER-DP resulted in more intracranial bleedings and a higher drop out rate due to headache compared with clopidogrel (5.9% versus 0.9%). 與clopidogrel 相比ASA +ER-DP的顱內出血率和因于頭疼的 脫落率較高。 1.European Atrial Fibri

27、llation trial (randomized placebo-controlled trial ) Numbers needed to treat (NNT) are 12/year. Result: warfarin :RRR 68% V 300 mg ASA: RRR 19% 2.The ACTIVE study Method: Randomized patients with AF into ASA + clopidogrel and warfarin groups. 將受試的具有房顫卒中病人隨機分為ASA+clopidogrel和華法令組 Result: terminated p

28、rematurely due to a significant reduction of stroke and systemic embolism in favour of warfarin. 由于華法令在降低中風發(fā)生和系統(tǒng)性栓塞方面表現出明顯的顯著性差異而提前終止。 rate of bleeding complications was not different between the two regimens. 在出血性并發(fā)癥方面兩者無明顯差異。 Prospective cohort studies have shown that treatment with aspirin or war

29、farin reduces the risk of recurrent stroke in the average patient with PFO to the same risk as in patients without PFO. 一項前瞻性隊列研究顯示：阿司匹林或華法令可將具有PFO的病人中風復發(fā)的危險性降至非PFO病人同等水平。 Suggest:Aspirin was as effective as anticoagulation and therefore should be given 建議：在防止PFO病人中風復方方面阿司匹林具有與抗凝劑同等效果，PFO病人應該服用。 1.E

30、SPIRIT (The Stroke Prevention in Reversible Ischemia trial) Aim:studied oral anticoagulation with an INR between3.0 and 4.5 versus 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和中風病人中，比較將INR控制在34.5的情況下服用抗凝劑和服用阿司匹林30mg的效果優(yōu)劣。 Result: terminated due to a significantly increased bleeding risk with anticoagulation. 因抗凝劑明顯增加出血性風險而中止。、 lower rate of ischaemic events with anticoagulation counterbalanced by an increased risk of intracranial bleedings. 抗凝劑降低缺