Hypertension

hypertensive patients with a cerebrovascular event within two years of randomisation. MOSES compared the only registered daily dose of eprosartan (600mg) with a suboptimal dose of nitrendipine. Mean daily doses at the end of the trial were 623mg for eprosartan and 16.2mg for nitrendipine.24 Trial,25

MOSES,24

For comparison, in the Systolic Hypertension in Europe the daily dose of nitrendipine averaged approximately 30mg. In the primary outcome was the composite of total mortality and

all cardiovascular and cerebrovascular events, including recurrent events. The incidence density ratio comparing eprosartan with nitrendipine was 0.79 (CI 0.66–0.96; p=0.014) for the composite end- point and 0.75 (CI 0.58–0.97; p=0.026) for stroke recurrence.24

In state-

of-the-art actuarial analyses only considering time to the first event within each category (with censoring), the hazard ratios were 0.69 (CI 0.50–0.97; p=0.031) for cardiovascular events and 0.88 (CI 0.65–1.20; p=0.42) for the first recurrent cerebrovascular complication.24

Interpretation

In our meta-analysis (see Figure 1), blood-pressure-lowering treatment across 10 trials (11 groups), including the perindopril only and the perindopril combined with indapamide arms of the PROGRESS trial,8 reduced the risk of recurrent stroke by 22%. In the trials involving diuretics as a component of therapy,9–11,14

the pooled reduction

As suggested by our meta-regression analysis, the significant heterogeneity (p<0.0001) between diuretics and renin system inhibitors in the prevention of stroke recurrence might be explained by the larger blood pressure reduction on treatment regimens involving diuretics. Whatever mechanism underlies the benefit of indapamide in the secondary7

and primary26 prevention of

stroke, our meta-analysis does not support the recommendation that prevention of stroke recurrence is a compelling indication for the use of angiotensin-converting enzyme inhibitors.27

n

1. Lopez AD, Mathers CD, Ezzqati M, et al., Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data, Lancet, 2006;367:1747–57.

2. Strong K, Mathers C, Bonita R, Preventing stroke: saving lives around the world, Lancet Neurol, 2007;6:182–7.

3. Mackay J, Mensah G, The Atlas of Heart Disease and Stroke,

World Health Organization, Geneva, Switzerland, 2004.

4. Staessen JA, Wang J, Bianchi G, Birkenhäger WH, Essential hypertension, Lancet, 2003;361:1629–41.

5. Luepker RV, Arnett DK, Jacobs DR, Jr, et al., Trends in blood pressure, hypertension control, and stroke mortality: the Minnesota Heart survey, Am J Med, 2006;119:42–9.

6. Wolf-Maier K, Cooper RS, Banegas JR, et al., Hypertension prevalence and blood-pressure levels in 6 European countries, Canada, and the United States, JAMA, 2003;289:2363–9.

7. Liu L, Wang Z, Gong L, et al.; for the Post-stroke Antihypertensive Treatment Study (PATS) Investigators, Blood pressure reduction for the secondary prevention of stroke: a Chinese trial and a systematic review of the literature, Hypertens Res, 2009;32:1032–40.

8. Yusuf S, Diener HC, Sacco RL, et al.; for the PRoFESS Study Group. Telmisartan to prevent recurrent stroke and

cardiovascular events, N Engl J Med, 2008;359:1225–37.

9. PATS Collaborative Group, Post-stroke antihypertensive treatment study. A preliminary result, Chin Med J, 1995;108:710–17.

10. Carter AB, Hypotensive therapy in stroke survivors, Lancet, 1970;1:485–9.

11. Hypertension-Stroke Cooperative Study Group, Effect of

antihypertensive treatment on stroke recurrence, JAMA, 1974;229:409–18.

12. The Dutch TIA Trial Study Group, Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke, Stroke 1993;24:543–8.

13. Eriksson S, Olofsson BO, Wester PO; for the TEST study group, Atenolol in secondary prevention after stroke,

Cerebrovasc Dis, 1995;5:21–5.

14. PROGRESS Collaborative Group, Randomised trial of a perindopril-based blood-pressure lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack, Lancet, 2001;358:1033–41.

15. Bosch J, Yusuf S, Pogue J, et al.; on behalf of the HOPE Investigators. Use of ramipril in preventing stroke: double blind randomised trial, BMJ, 2002;324:1–5.

16. 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;14:31–7.

17. Liu L, Zhao Y, Liu G, et al.; for the FEVER Study Group. The Felodipine Event Reduction (FEVER) Study: a randomized long-term placebo-controlled trial in Chinese hypertensive patients, J Hypertens, 2005;23:2157–72.

18. PROGRESS Management Committee, PROGRESS – Perindopril Protection Against Recurrent Stroke Study: characteristics of the study population at baseline,

J Hypertens, 1999;17:1647–55.

19. The 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;342:145–53.

20. Lithell H, Hansson L, Skoog I, et al.; for the SCOPE Study Group. The study on cognition and prognosis in the elderly (SCOPE). Principal results of a randomised double-blind intervention trial, J Hypertens, 2003;21:875–86.

21. Holmer SR, Hense HW, Danser AHJ, et al., β-Adrenergic blockers lower renin in patients treated with ACE inhibitors and diuretics, Heart, 1998;80:45–8.

22. Staessen JA, Li Y, Richart T, Oral renin inhibitors, Lancet, 2006;346:1449–56.

23. Liu LS, Gong LS, Wang W; Blood Pressure Lowering to Prevent Recurrent Stroke Study Group, Effects of blood pressure lowering treatment on stroke recurrence in patients with cerebrovascular diseases—a large-scale, randomized, placebo controlled trial, Chin J Cardiol, 2005;33: 613–17.

24. Schrader J, Luders S, Kulschewski A, et al., Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention. Principal results of a prospective randomized controlled study (MOSES), Stroke, 2005;36:1218–26.

25. Staessen JA, Fagard R, Thijs L, et al., Randomised double- blind comparison of placebo and active treatment for older patients with isolated systolic hypertension, Lancet, 1997;350:757–64. Erratum: Lancet, 1997;350:1636.

26. Beckett NS, Peters R, Fletcher AE, et al.; for the HYVET Study Group. Treatment of hypertension in patients 80 years of age or older, N Engl J Med, 2008;358:1887–98.

27. Chobanian AV, Bakris GL, Black HR, et al., Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure, Hypertension, 2003;42:1206–52.

averaged 37%, whereas it was only 7% in the trials of renin system inhibitors.8,12–15

Zengwu Wang is an Associate Professor of Cardiology and Epidemiology at Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing. His research interests include the epidemiology, prevention and treatment of cardiovascular disease. He is one of the lead investigators of the Hypertension Control in Community (HCC) study, a programme designed to improve the treatment and control of hypertension in China. He is the Director of the Beijing Hypertension Association and the Chinese Hypertension League. He received his medical and doctoral degrees from the Chinese Academy of Medical Sciences.

Tom Richart is a doctoral student in the Department of Epidemiology at Maastricht University. His main research interests are vascular mechanics, cardio-metabolic disease and gene–environment interactions affecting metabolism and cardiovascular structure and function. He received his medical degree from Antwerp University and his MSc in biomedical and clinical engineering from Ghent University.

Yu Jin is a doctoral student at the Studies Co-ordinating Centre at the University of Leuven. Her research interests focus on the genetic and environmental determinants of cardiac structure and function and cardiovascular epidemiology. She received her medical degree from the Nanjing Medical University in China.

Jan A Staessen is Head of the Studies Co-ordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases at the University of Leuven. In addition, he is a Professor of Genetic Epidemiology in the Department of Epidemiology at Maastricht University. Professor Staessen has been the principal investigator of several influential trials, such as Syst-Eur, APTH and THOP. He chairs the European Hypertension Society Working Group on Blood Pressure Monitoring and is an International Fellow of the Council for High Blood Pressure Research of the American Heart Association (AHA).

Lisheng Liu is Vice Director of the National Centre for Cardiovascular Disease, China, Director of the Beijing Hypertension League Institute and a Professor of Medicine at Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing. She is President of the World Hypertension League and the Chinese Hypertension League. Since 1985, she has led many cardiovascular clinical trials in China, such as Syst.-China, PATS, INTERHEART, FEVER, CCS-1, CAST, CREATE, ONTARGET, POSIE, RELY, and HYVET. She received her medical degree from Peking Union Medical College, Beijing, and completed her post-doctoral research at the Hypertension Research Center, Medical College of Alabama at Birmingham.

40

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