Efficacy of different renin-angiotensin system blockers in patients with prior stroke: a network meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

YANG Dahong , JIA Yujuan ,  HOU Yuli

The First Hospital of Shanxi Medical University, Taiyuan, 030001, P.R.China;

Corresponding author：

HOU Yuli, Email: houyuli2008@163.com

Keywords：

Stroke; Secondary prevention; Renin-angiotensin system blocker; Angiotensin-converting enzyme inhibitor; Angiotensin receptor blocker; Network meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.201901047

Video：

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Objectives To systematically review the efficacy of different rennin-angiotensin system blockers in prevention of stroke recurrence and reduction of major vascular events in patients with prior stroke.Methods PubMed, The Cochrane Library, EMbase, CNKI, CBM and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy of ACEIs and ARBs for stroke secondary prevention from inception to November 1^st, 2018. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Network meta-analysis was then performed by using Stata 15.1 software.Results A total of 6 RCTs involving 25 620 patients were included. The results of network meta-analysis showed that: in prevention of stroke recurrence, candesartan (RR=0.40, 95%CI 0.16 to 0.99) and valsartan (RR=0.22, 95%CI 0.07 to 0.76) were significantly lower than placebo; valsartan was lower than telmisartan (RR=0.24, 95%CI 0.07 to 0.81), ramipril (RR=0.26, 95%CI 0.07 to 0.93) and perindopril (RR=0.23, 95%CI 0.07 to 0.81). For reducing the major vascular events after stroke, candesartan (RR=0.39, 95%CI 0.21 to 0.74), valsartan (RR=0.27, 95%CI 0.11 to 0.64) and ramipril (RR=0.76, 95%CI 0.60 to 0.95) were significantly lower than placebo; valsartan was lower than telmisartan (RR=0.29, 95%CI 0.12 to 0.69), ramipril (RR=0.36, 95%CI 0.15 to 0.88) and perindopril (RR=0.28, 95%CI 0.12 to 0.68); candesartan was lower than telmisartan (RR=0.42, 95%CI 0.22 to 0.79) and perindopril (RR=0.41, 95%CI 0.21 to 0.79).Conclusions Current evidence shows that valsartan and candesartan can reduce the stroke recurrence and major vascular events after stroke. Ramipril can reduce the major vascular event in patients with prior stroke. Valsartan might be the best option in both outcomes. Due to limited quantity of the included studies, more high quality studies are required to verify above conclusions.

Citation： YANG Dahong, JIA Yujuan, HOU Yuli. Efficacy of different renin-angiotensin system blockers in patients with prior stroke: a network meta-analysis. Chinese Journal of Evidence-Based Medicine, 2019, 19(10): 1203-1210. doi: 10.7507/1672-2531.201901047 Copy

1.	GBD 2016 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet, 2017, 390(10100): 1260-1344.
2.	Mohan KM, Wolfe CD, Rudd AG, et al. Risk and cumulative risk of stroke recurrence: a systematic review and meta-analysis. Stroke, 2011, 42(5): 1489-1494.
3.	Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA, 2000, 284(22): 2901-2906.
4.	杨卉, 王赤波, 梁辉. 肾素-血管紧张素系统与卒中. 国外医学 (脑血管疾病分册), 2001, 9(4): 227-229.
5.	梁辉, 范金英, 周盛年. 肾素-血管紧张素系统与缺血性脑血管病. 中华神经医学杂志, 2003, (4): 312-314.
6.	Saavedra JM, Benicky J, Zhou J. Mechanisms of the anti-ischemic effect of angiotensin Ⅱ at (1) receptor antagonists in the Brain. Cell Mol Neurobiol, 2006, 26(7-8): 1099-1111.
7.	Wang WT, You LK, Chiang CE, et al. Comparative effectiveness of blood pressure-lowering drugs in patients who have already suffered from stroke: traditional and bayesian network meta-analysis of randomized trials. Medicine, 2016, 95(15): e3302.
8.	Lee M, Saver JL, Hong KS, et al. Renin-angiotensin system modulators modestly reduce vascular risk in persons with prior stroke. Stroke, 2012, 43(1): 113-119.
9.	Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation, 2018, 138(17): e426-e483.
10.	李伦, 田金徽, 姚亮, 等. 网状 Meta 分析的统计学基础、假设和证据质量评估. 循证医学, 2015, 15(3): 180-183.
11.	Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med, 2015, 162(11): 777-784.
12.	Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ, 2003, 327(7414): 557-560.
13.	Macaskill P, Walter SD, Irwig L. A comparison of methods to detect publication bias in meta-analysis. Stat Med, 2001, 20(4): 641-654.
14.	Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
15.	Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol, 2011, 64(2): 163-171.
16.	Ogihara T, Nakao K, Fukui T, et al. The optimal target blood pressure for antihypertensive treatment in Japanese elderly patients with high-risk hypertension: a subanalysis of the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial. Hypertens Res, 2008, 31(8): 1595-1601.
17.	Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med, 2000, 342(3): 145-153.
18.	Sleight P, Yusuf S, Pogue J, et al. Blood-pressure reduction and cardiovascular risk in HOPE study. Lancet, 2001, 358(9299): 2130-2131.
19.	Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke, 2003, 34(11): 2741-2748.
20.	Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ, 2002, 324(7339): 699-702.
21.	Yusuf S, Diener HC, Sacco RL, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med, 2008, 359(12): 1225-1237.
22.	Weinberger J. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Curr Cardiol Rep, 2003, 5(2): 140.
23.	Trenkwalder P, Elmfeldt D, Hofman A, et al. The Study on COgnition and Prognosis in the Elderly (SCOPE)-major CV events and stroke in subgroups of patients. Blood Press, 2005, 14(1): 31-37.
24.	Zanchetti A, Julius S, Kjeldsen S, et al. Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial. J Hypertens, 2006, 24(11): 2163-2168.
25.	中国脑卒中防治血压管理指导规范. 中国脑卒中防治血压管理指导规范. 实用心脑肺血管病杂志, 2017, 25(10): 87.
26.	Savaskan E. The role of the brain renin-angiotensin system in neurodegenerative disorders. Curr Alzheimer Res, 2005, 2(1): 29-35.
27.	王拥军. 血管紧张素受体拮抗剂在改善脑卒中患者预后中的作用. 中华高血压杂志, 2012, 20(5): 411-413.
28.	姜馨, 吕卓人. 血管紧张素Ⅱ受体拮抗剂和血管紧张素转换酶抑制剂的脑保护作用之差异. 中华心血管病杂志, 2006, 34(12): 1143-1145.
29.	Vidt DG. Telmisartan, ramipril, or both in patients at high risk for vascular events. Curr Hypertens Rep, 2008, 10(5): 343-344.
30.	Diener HC. Preventing stroke: the PRoFESS, ONTARGET, and TRANSCEND trial programs. J Hypertens Suppl, 2009, 27(5): S31-S36.
31.	曾宪涛, 沈可, 罗杰. Meta 分析系列之十二: 分配隐藏的评价. 中国循证心血管医学杂志, 2013, 5(3): 219-221.
32.	曾宪涛, 熊期, 沈可. Meta 分析系列之十三: 盲法的评价. 中国循证心血管医学杂志, 2013, 5(4): 331-333.
33.	Schrader J, Lüders S, Kulschewski A, et al. The ACCESS Study: evaluation of acute candesartan cilexetil therapy in stroke survivors. Stroke, 2003, 34(7): 1699-1703.
34.	Jusufovic M, Sandset EC, Bath PM, et al. Effects of blood pressure lowering in patients with acute ischemic stroke and carotid artery stenosis. Int J Stroke, 2015, 10(3): 354-359.
35.	中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南 2018. 中华神经科杂志, 2018, 51(9): 666-682.
36.	国家卫生健康委员会急诊医学质控中心, 中国医师协会急诊医师分会, 世界中医药学会联合会急症专业委员会. 中国急性缺血性脑卒中急诊诊治专家共识. 中国急救医学, 2018, 38(4): 281-287.

1. GBD 2016 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet, 2017, 390(10100): 1260-1344.
2. Mohan KM, Wolfe CD, Rudd AG, et al. Risk and cumulative risk of stroke recurrence: a systematic review and meta-analysis. Stroke, 2011, 42(5): 1489-1494.
3. Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA, 2000, 284(22): 2901-2906.
4. 杨卉, 王赤波, 梁辉. 肾素-血管紧张素系统与卒中. 国外医学 (脑血管疾病分册), 2001, 9(4): 227-229.
5. 梁辉, 范金英, 周盛年. 肾素-血管紧张素系统与缺血性脑血管病. 中华神经医学杂志, 2003, (4): 312-314.
6. Saavedra JM, Benicky J, Zhou J. Mechanisms of the anti-ischemic effect of angiotensin Ⅱ at (1) receptor antagonists in the Brain. Cell Mol Neurobiol, 2006, 26(7-8): 1099-1111.
7. Wang WT, You LK, Chiang CE, et al. Comparative effectiveness of blood pressure-lowering drugs in patients who have already suffered from stroke: traditional and bayesian network meta-analysis of randomized trials. Medicine, 2016, 95(15): e3302.
8. Lee M, Saver JL, Hong KS, et al. Renin-angiotensin system modulators modestly reduce vascular risk in persons with prior stroke. Stroke, 2012, 43(1): 113-119.
9. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation, 2018, 138(17): e426-e483.
10. 李伦, 田金徽, 姚亮, 等. 网状 Meta 分析的统计学基础、假设和证据质量评估. 循证医学, 2015, 15(3): 180-183.
11. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med, 2015, 162(11): 777-784.
12. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ, 2003, 327(7414): 557-560.
13. Macaskill P, Walter SD, Irwig L. A comparison of methods to detect publication bias in meta-analysis. Stat Med, 2001, 20(4): 641-654.
14. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
15. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol, 2011, 64(2): 163-171.
16. Ogihara T, Nakao K, Fukui T, et al. The optimal target blood pressure for antihypertensive treatment in Japanese elderly patients with high-risk hypertension: a subanalysis of the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial. Hypertens Res, 2008, 31(8): 1595-1601.
17. Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med, 2000, 342(3): 145-153.
18. Sleight P, Yusuf S, Pogue J, et al. Blood-pressure reduction and cardiovascular risk in HOPE study. Lancet, 2001, 358(9299): 2130-2131.
19. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke, 2003, 34(11): 2741-2748.
20. Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ, 2002, 324(7339): 699-702.
21. Yusuf S, Diener HC, Sacco RL, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med, 2008, 359(12): 1225-1237.
22. Weinberger J. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Curr Cardiol Rep, 2003, 5(2): 140.
23. Trenkwalder P, Elmfeldt D, Hofman A, et al. The Study on COgnition and Prognosis in the Elderly (SCOPE)-major CV events and stroke in subgroups of patients. Blood Press, 2005, 14(1): 31-37.
24. Zanchetti A, Julius S, Kjeldsen S, et al. Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial. J Hypertens, 2006, 24(11): 2163-2168.
25. 中国脑卒中防治血压管理指导规范. 中国脑卒中防治血压管理指导规范. 实用心脑肺血管病杂志, 2017, 25(10): 87.
26. Savaskan E. The role of the brain renin-angiotensin system in neurodegenerative disorders. Curr Alzheimer Res, 2005, 2(1): 29-35.
27. 王拥军. 血管紧张素受体拮抗剂在改善脑卒中患者预后中的作用. 中华高血压杂志, 2012, 20(5): 411-413.
28. 姜馨, 吕卓人. 血管紧张素Ⅱ受体拮抗剂和血管紧张素转换酶抑制剂的脑保护作用之差异. 中华心血管病杂志, 2006, 34(12): 1143-1145.
29. Vidt DG. Telmisartan, ramipril, or both in patients at high risk for vascular events. Curr Hypertens Rep, 2008, 10(5): 343-344.
30. Diener HC. Preventing stroke: the PRoFESS, ONTARGET, and TRANSCEND trial programs. J Hypertens Suppl, 2009, 27(5): S31-S36.
31. 曾宪涛, 沈可, 罗杰. Meta 分析系列之十二: 分配隐藏的评价. 中国循证心血管医学杂志, 2013, 5(3): 219-221.
32. 曾宪涛, 熊期, 沈可. Meta 分析系列之十三: 盲法的评价. 中国循证心血管医学杂志, 2013, 5(4): 331-333.
33. Schrader J, Lüders S, Kulschewski A, et al. The ACCESS Study: evaluation of acute candesartan cilexetil therapy in stroke survivors. Stroke, 2003, 34(7): 1699-1703.
34. Jusufovic M, Sandset EC, Bath PM, et al. Effects of blood pressure lowering in patients with acute ischemic stroke and carotid artery stenosis. Int J Stroke, 2015, 10(3): 354-359.
35. 中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南 2018. 中华神经科杂志, 2018, 51(9): 666-682.
36. 国家卫生健康委员会急诊医学质控中心, 中国医师协会急诊医师分会, 世界中医药学会联合会急症专业委员会. 中国急性缺血性脑卒中急诊诊治专家共识. 中国急救医学, 2018, 38(4): 281-287.

Chinese Journal of Evidence-Based Medicine

Efficacy of different renin-angiotensin system blockers in patients with prior stroke: a network meta-analysis

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