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Drug Therapy for the Secondary Prevention of Stroke in Hypertensive Patients

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Abstract

Hypertension is the major risk factor for ischaemic and haemorrhagic clinical strokes as well as for silent brain infarcts with a continuous association between both systolic and diastolic blood pressures. Epidemiological data highlight the increasing burden to come over the next decades. Without any doubt, antihypertensive treatment is the most important therapy to reduce the risk of stroke by approximately 30–40%. International guidelines recommend antihypertensive treatment for primary prevention with evidence level A.

Recurrent strokes or transient ischaemic attack (TIA) are an important practical, clinical and economic problem, and have a major impact on the development of vascular dementia. All stroke patients and patients with TIA have to be regarded as very high-risk patients. Hypertension increases the risk of recurrent strokes. Only limited data directly address the role of blood pressure treatment among individuals with stroke or TIA.

There is a general lack of definitive data regarding when to start antihypertensive treatment in the initial phase, and treatment of hypertension in the acute period after stroke is still under debate. Experimental and clinical data suggest that reducing the activity of the renin-angiotensin aldosterone system (RAAS) may have beneficial effects beyond the lowering of blood pressure. There is increasing evidence of cerebroprotective effects for medication influencing the RAAS, such as angiotensin receptor antagonists or ACE inhibitors. The MOSES study showed for the first time superiority of an angiotensin receptor antagonist compared with a calcium channel antagonist in antihypertensive treatment for secondary stroke prevention. Optimal blood pressure range in secondary prevention seems to be 120–140/80–90mm Hg, but questions about a J-or U-shaped curve are still not answered sufficiently. The effects of additional antihypertensive treatment in the evening for stroke patients with ‘non-dipping’ blood pressure need to be investigated.

Currently, the most important goal in primary and secondary prevention of stroke is a strict normotensive blood pressure control. Antihypertensive treatment is recommended for both prevention of recurrent stroke and prevention of other vascular events in individuals who have had an ischaemic stroke or TIA (class I, level of evidence A). Many open questions remain and funding of stroke research needs to be increased in the near future.

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References

  1. Feigin VL, Lawes CM, Bennett DA, et al. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case fatality in the late 20th century. Lancet Neurol 2003; 2: 43–53

    Article  PubMed  Google Scholar 

  2. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217–23

    PubMed  Google Scholar 

  3. Rothwell PM, Coull AJ, Silver LE, et al. Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 2005; 366: 1773–83

    Article  PubMed  CAS  Google Scholar 

  4. Leppala JM, Virtamo J, Fogelholm R, et al. Different risk factors for different stroke subtypes: association of blood pressure, cholesterol, and antioxidants. Stroke 1999; 30 (12): 2535–40

    Article  PubMed  CAS  Google Scholar 

  5. 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 (6): 1206–52

    Article  PubMed  CAS  Google Scholar 

  6. Lawes CMM, Bennett DA, Feigin VL, et al. Blood pressure and stroke: an overview of published reviews. Stroke 2004; 35: 776–85

    Article  PubMed  Google Scholar 

  7. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342 (3): 145–53

    Article  PubMed  CAS  Google Scholar 

  8. Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002; 324: 699–702

    Article  PubMed  CAS  Google Scholar 

  9. Schrader J, Lüders S. Preventing stroke. BMJ 2002; 324: 687–8

    Article  PubMed  Google Scholar 

  10. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003

    Article  PubMed  CAS  Google Scholar 

  11. Moen MD, Wagstaff AJ. Losartan: a review of its use in stroke risk reduction in patients with hypertension and left ventricular hypertrophy. Drugs 2005; 65 (18): 2657–74

    Article  PubMed  CAS  Google Scholar 

  12. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366: 1545–53

    Article  PubMed  CAS  Google Scholar 

  13. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–97

    Article  Google Scholar 

  14. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022–31

    Article  PubMed  CAS  Google Scholar 

  15. Goldstein LB, Hankey GJ. Advances in primary stroke prevention. Stroke 2006; 37: 317–9

    Article  PubMed  Google Scholar 

  16. Grau AJ, Weimar C, Buggle F, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 2001; 332: 2559–66

    Article  Google Scholar 

  17. Hardie K, Hankey GJ, Jamrozik K, et al. Ten-year risk of first recurrent stroke and disability after first-ever stroke in the Perth Community Stroke Study. Stroke 2004 Mar; 35 (3): 731–5

    Article  PubMed  Google Scholar 

  18. Coull AJ, Lovett JK, Rothwell PM. Oxford Vascular Study: population based study of early risk of stroke after transient ischaemic attack or minor strokeimplications for public education and organisation of services. BMJ 2004; 328 (7435): 326

    Article  PubMed  CAS  Google Scholar 

  19. Vernino S, Brown Jr RD, Sejvar JJ, et al. Cause-specific mortality after first cerebral infarction: a population-based study. Stroke 2003 Aug; 34 (8): 1828–32

    Article  PubMed  Google Scholar 

  20. Adams RJ, Chimowitz MI, Alpert JS, et al. Coronary risk evaluation in patients with transient ischemic attack and ischemic stroke: a scientific statement for healthcare professionals from the Stroke Council and the Council on Clinical Cardiology of the American Heart Association/American Stroke Association. Stroke 2003; 34 (9): 2310–22

    Article  PubMed  Google Scholar 

  21. Kolominsky-Rabas PL, Heuschmann PU, Marschall D, et al. Lifetime cost of ischemic stroke in Germany: results and national projections from a population-based stroke registry. The Erlangen Stroke Project. Stroke 2006; 37: 1179–83

    Google Scholar 

  22. Hill MD, Yiannakoulias N, Jeerakthil T, et al. The high risk of stroke immediately after transient ischemic attack: a population-based study. Neurology 2004; 62: 2015–20

    Article  PubMed  CAS  Google Scholar 

  23. Fotherby MD, Panayiotou B. Antihypertensive therapy in the prevention of stroke. Drugs 1999; 58 (4): 663–74

    Article  PubMed  CAS  Google Scholar 

  24. Pendlebury ST, Rothwell PM, Algra A, et al. Underfunding of stroke research: a Europe-wide problem. Stroke 2004 Oct; 35 (10): 2368–71

    Article  PubMed  Google Scholar 

  25. Cheng E, Chen A, Vassar S, et al. Comparison of secondary prevention care after myocardial infarction and stroke. Cerebrovasc Dis 2006; 21: 235–41

    Article  PubMed  Google Scholar 

  26. Lees KR, Bath PM, Naylor AR. ABC of arterial and venous disease: secondary prevention of transient ischaemic attack and stroke. BMJ 2000; 320 (7240): 991–4

    Article  PubMed  CAS  Google Scholar 

  27. Rodgers A, MacMahon S, Gamble G, et al. Blood pressure and risk of stroke in patients with cerebrovascular disease: the United Kingdom Transient Ischaemic Attack Collaborative Group. BMJ 1996; 313 (7050): 147

    Article  PubMed  CAS  Google Scholar 

  28. Pedelty L, Gorelick PB. Chronic management of blood pressure after stroke. Hypertension 2004; 44: 1–5

    Article  PubMed  CAS  Google Scholar 

  29. Toyoda K, Okada Y, Fujimoto S, et al. Blood pressure changes during the initial week after different subtypes of ischemic stroke. Stroke 2006; 37: 2637–9

    Article  PubMed  Google Scholar 

  30. Perez A, Restrepo L, Kleinman JT, et al. Patients with diffusion-perfusion mismatch on magnetic resonance imaging 48 hours or more after stroke symptom onset: clinical and imaging features. J Neuroimaging 2006 Oct; 16 (4): 329–33

    Article  PubMed  Google Scholar 

  31. Adams HP, Adams RJ, Brott T, et al. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke 2003; 34: 1056–83

    Article  PubMed  Google Scholar 

  32. Ovbiagele B. The emergency department: first line of defense in preventing secondary stroke. Acad Emerg Med 2006; 13 (2): 215–22

    Article  PubMed  Google Scholar 

  33. Chalmers J. Blood pressure in acute stroke: in search of evidence. J Hypertens 2005; 23: 277–8

    Article  PubMed  CAS  Google Scholar 

  34. Castillo J, Leira R, Garcia MM. Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome. Stroke 2004; 35: 520–7

    Article  PubMed  Google Scholar 

  35. Johansson BB. Hypertension mechanisms causing stroke. Clin Exp Pharmacol Physiol 1999; 26 (7): 563–5

    Article  PubMed  CAS  Google Scholar 

  36. Fagan SC, Kozak A, Hill WD, et al. Hypertension after experimental cerebral ischemia: candesartan provides neurovascular protection. J Hypertens 2006 Mar; 24 (3): 535–9

    Article  PubMed  CAS  Google Scholar 

  37. Bandera E, Botteri M, Minelli C, et al. Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke 2006; 37: 1334–9

    Article  PubMed  Google Scholar 

  38. Abboud H, Labreuche J, Ploin F, et al. High blood pressure in early acute stroke: a sign of a poor outcome? J Hypertens 2006; 24: 381–6

    Article  PubMed  CAS  Google Scholar 

  39. Schrader J, Luders S, Kulschewski A, et al. The ACCESS study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke 2003; 34: 1699–703

    Article  PubMed  Google Scholar 

  40. Scandinavian Candesartan Acute Stroke Trial [online]. Available from URL: http://www.scast.no/ [Accessed 2007 Mar 13]

  41. The COSSACS Trial Group. COSSACS (Continue or Stop post-Stroke Antihypertensives Collaborative Study): rationale and design. J Hypertens 2005, 23: 455–8

    Article  Google Scholar 

  42. The CHHIPS Trial Group. CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: ratio-nale and design. J Hypertens 2005; 23: 649–55

    Article  Google Scholar 

  43. 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: 2741–8

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  45. Nilsson PM. Reducing the risk of stroke in elderly patients with hypertension. Drugs Aging 2005; 22 (6): 517–24

    Article  PubMed  CAS  Google Scholar 

  46. Kirshner HS, Biller J, Callahan AS. Long-term therapy to prevent stroke. J Am Board Fam Pract 2005; 18: 528–40

    Article  PubMed  Google Scholar 

  47. Elliot WJ, Jonsson MC, Black HR. Management of hypertension: is it the pressure or the drug? It is not beyond the blood pressure; it is the blood pressure. Circulation 2006; 113: 2754–74

    Article  Google Scholar 

  48. Sever PS, Poulter NR. Management of hypertension: is it the pressure or the drug? Blood pressure reduction is not the only determinant of outcome. Circulation 2006; 113: 2754–74

    Article  PubMed  Google Scholar 

  49. Svensson P, de Faire U, Sleight P, et al. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE substudy. Hypertension 2001; 38: e28–32

    Article  PubMed  CAS  Google Scholar 

  50. 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 (6): 1218–26

    Article  PubMed  CAS  Google Scholar 

  51. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension: the Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350: 757–64

    Article  PubMed  CAS  Google Scholar 

  52. McDonald MA, Simpson SH, Ezekowitz JA, et al. Angiotensin receptor blockers and risk of myocardial infarction: systematic review. BMJ 2005; 331: 873

    Article  PubMed  CAS  Google Scholar 

  53. Lüders S, Kulschewski A, Hammersen F, et al. ARB and myocardial infarction: safety aspects in patients with history of stroke: analysis from the MOSES study (eprosartan compared with nitrendipine for secondary prevention of stroke) [online]. Available from URL: "http://www.bmj.com/cgi/eletters/331/7521/873#123771 [Accessed 2007 Apr 4]

  54. Tsuyuki RT, McDonald MA, Strauss MH, et al. Angiotensin receptor blockers do not increase risk of myocardial infarction. Circulation 2006; 114: 855–60

    Article  PubMed  Google Scholar 

  55. Strauss MH, Hall AS, Tsuyuki RT, et al. Angiotensin receptor blockers may increase risk of myocardial infarction: unrav-eling the ARB-MI paradox. Circulation 2006; 114: 838–54

    Article  PubMed  Google Scholar 

  56. 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: 2163–8

    Article  PubMed  CAS  Google Scholar 

  57. Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectivelydesigned overviews of randomised trials. Lancet 2003; 362: 1527–35

    Article  PubMed  CAS  Google Scholar 

  58. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. A statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 2006; 37: 577–617

    Google Scholar 

  59. Diener HC. Kommission Leitlinien der DSG: Leitlinie Primärund Sekundärprävention der zerebralen Ischämie. Stuttgart: Thieme Verlag, 2005: 3

  60. Ovbiagele B, Hills NK, Saver JL, et al. Antihypertensive medications prescribed at discharge after an acute ischemic cerebrovascular event. Stroke 2005; 36 (9): 1944–7

    Article  PubMed  Google Scholar 

  61. Ovbiagele B, Hills NK, Saver JL, et al. Secondary-prevention drug prescription in the very elderly after ischemic stroke or TIA. Neurology 2006; 66 (3): 313–8

    Article  PubMed  Google Scholar 

  62. Diener HC. Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS): rationale and design. Cerebrovasc Dis 2000; 10: 147–50

    Article  Google Scholar 

  63. Teo K, Yusuf S, Anderson C, et al. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Ran-domized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J 2004; 148: 52–61

    Article  PubMed  Google Scholar 

  64. Tsouli SG, Liberopoulos EN, Kiortsis DN, et al. Combined treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a review of the current evi-dence. J Cardiovasc Pharmacol Ther 2006; II(I): 1–15

    Article  Google Scholar 

  65. Ferro CJ, Webb DJ. The clinical potential of endothelin receptor antagonists in cardiovascular medicine. Drugs 1996 Jan; 51 (1): 12–27

    Article  PubMed  CAS  Google Scholar 

  66. Love MP, McMurray JJV. Endothelin receptor antagonists and cardiovascular diseases of aging. Drugs Aging 2001; 18 (6): 425–40

    Article  PubMed  CAS  Google Scholar 

  67. Zhang Y, Belayev L, Zhao W, et al. A selective endothelin ET(A) receptor antagonist, SB 234551, improves cerebral perfusion following permanent focal cerebral ischemia in rats. Brain Res 2005; 1045 (1–2): 150–6

    Article  PubMed  CAS  Google Scholar 

  68. Yamamoto Y, Akiguchi I, Oiwa K, et al. Adverse effect of nighttime blood pressure on the outcome of lacunar infarct patients. Stroke 1998; 29 (3): 570–6

    Article  PubMed  CAS  Google Scholar 

  69. Schrader J, Lüders S, Züchner C, et al. Practice vs ambulatory blood pressure measurement under treatment with ramipril (PLUR study): a randomised, prospective long-term study to evaluate the benefits of ABPM in patients on antihypertensive treatment. J Hum Hypertens 2000; 14 (7): 435–40

    Article  PubMed  CAS  Google Scholar 

  70. Pickering TG, Shimbo D, Haas D. Ambulatory blood pressure monitoring. N Engl J Med 2006; 354: 2368–74

    Article  PubMed  CAS  Google Scholar 

  71. Anwar YA, White WB. Chronotherapeutics for cardiovascular disease. Drugs 1998; 55 (5): 631–43

    Article  PubMed  CAS  Google Scholar 

  72. Fujiwara N, Osanai T, Baba Y, et al. Nocturnal blood pressure decrease is associated with increased regional cerebral blood flow in patients with a history of ischemic stroke. J Hypertens 2005; 23: 1055–60

    Article  PubMed  CAS  Google Scholar 

  73. Sierra C, Coca A. Nocturnal fall of blood pressure with antihypertensive therapy and recurrence of ischemic stroke: ‘the lower the better’ revisited. J Hypertens 2005; 23: 1131–2

    Article  PubMed  CAS  Google Scholar 

  74. Metoki H, Ohkubo T, Kikuya M, et al. Prognostic significance for stroke of a morning pressure surge and a nocturnal blood pressure decline: the Ohasama Study. Hypertension 2006; 47: 149–54

    Article  PubMed  CAS  Google Scholar 

  75. Okumura K, Ohya Y, Maehara A, et al. Effects of blood pressure levels on case fatality after acute stroke. J Hypertens 2005; 23: 1217–23

    Article  PubMed  CAS  Google Scholar 

  76. Leonardi-Bee J, Bath PM, Phillips SJ, et al. Blood pressure and clinical outcomes in the International Stroke Trial. Stroke 2002; 33 (5): 1315–20

    Article  PubMed  Google Scholar 

  77. Lübcke C, Lüders S, Hammersen F, et al. Target blood pressure after stroke: is tehre a J-curve? Subgroup analyses of the MOSES study (Morbidity and mortality after Stroke, Eprop-sartan compared with nitrendipine for Secondary prevention) [abstract]. Dtsch Med Wochenschr 2006; 131: S159

    Article  Google Scholar 

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No sources of funding were used to assist in the preparation of this manuscript. The author has no conflicts of interest that are directly relevant to the content of this review.

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    Stephan Lüders

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Lüders, S. Drug Therapy for the Secondary Prevention of Stroke in Hypertensive Patients. Drugs 67, 955–963 (2007). https://doi.org/10.2165/00003495-200767070-00001

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