title: Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of stroke recurrence and longitudinal progression of white matter lesions and silent brain infarcts on MRI (CEREBRAL study): rationale, design, and methodology.
abstract: OBJECTIVE
  Patients with a history of ischemic stroke are known to develop new ischemic stroke. While asymptomatic, the presence and progression of silent brain infarcts and white matter lesions on magnetic resonance imaging are associated with an increased risk of future strokes. Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are recommended for the primary and secondary prevention of stroke, but there are no direct comparisons of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers regarding their cerebroprotective effects, including their effect on asymptomatic cerebral lesions detected by magnetic resonance imaging.
  
  
  METHODS
  Elderly (65 years or older) patients with essential hypertension who underwent cerebral magnetic resonance imaging and were found to have any cerebral ischemic lesions, such as cerebral infarction, silent brain infarct, or white matter lesion, were enrolled in this CEREBRAL study. Patients who agreed to participate were enrolled in the randomized controlled trial portion. Patients who did not agree to participate in the randomized controlled trial were enrolled in the cohort study portion. After two-years of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers treatment, follow-up magnetic resonance imaging examination will be performed. The primary end-point is the composite of (1) occurrence of a fatal or nonfatal cerebrovascular event or (2) progression of cerebrovascular lesions as evaluated by magnetic resonance imaging, including white matter lesions or silent brain infarcts. After enrollment, cognitive function was evaluated, if possible, using the Mini-Mental State Examination.
  
  
  CONCLUSIONS
  Our study will clarify whether angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are more effective for preventing primary and recurrence of ischemic stroke, including the progression of asymptomatic cerebral lesions on magnetic resonance imaging, in elderly hypertensive patients.
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Japan; Department of Internal Medicine, Nara Prefectural General Rehabilitation Center, Shiki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamano
authors.forename: Manabu
authors.initials: M
authors.lastname: Horii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takami
authors.forename: Mio
authors.initials: M
authors.lastname: Sakuma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morimoto
authors.forename: Sadanori
authors.initials: S
authors.lastname: Okada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Taoka
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kichikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furuya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueno
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Imamura
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000209:etiology; D015331:Cohort Studies; D018450:Disease Progression; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017063:Outcome Assessment, Health Care; D012008:Recurrence; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D066127:White Matter / Q000473:pathology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: angiotensin II receptor blockers; angiotensin-converting enzyme inhibitors; asymptomatic cerebral lesion; hypertension; magnetic resonance imaging; stroke recurrence