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

Authors


  • Conflict of interest: Takeshi Morimoto received lecture fees from Bayer Yakuhin Co. Ltd, Boehringer Ingelheim, Inc., Edwards Lifesciences, LLC., Eisai Co.,Ltd, Japan Tabacco Inc., Kowa Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co. Ltd,Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd, and research fundings from Bayer Yakuhin Co. Ltd, Eisai Co. Ltd, Japan Tabacco Inc., Kowa Co. Ltd. Hisao Ogawa received lecture fees from Bayer Yakuhin Co. Ltd, Boehringer Ingelheim, Inc., Daiichi Sankyo Co. Ltd, MSDCo.,Ltd, Pfizer Japan Inc., Sanofi-Aventis Co. Ltd, and research fundings from Astellas Pharma Inc., AstraZeneca K.K., Bayer Yakuhin Co. Ltd, Boehringer Ingelheim, Inc., Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Dainippon Sumitomo Pharmaceutical Co. Ltd, Eisai Co. Ltd, Japan Heart Foundation, Kowa Co, Ltd, MSD Co. Ltd, Novartis Pharma K.K., Otsuka Pharmaceutical Co. Ltd, Pfizer Japan Inc., Sanofi-Aventis Co. Ltd, Shionogi & Co., Ltd. Takeda Pharmaceutical Co. Ltd, and The Waksman Foundation of Japan Inc.
  • Yoshihiko Saito received lecture fees from Merck &Co., Inc., Takeda Pharmaceutical Co. Ltd, Novartis Pharma K.K., Daiichi Sankyo Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Otsuka Pharmaceutical Co. Ltd, and research fundings from Merck & Co., Inc., Takeda Pharmaceutical Co. Ltd, Novartis Pharma K.K., Daiichi Sankyo Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Otsuka Pharmaceutical Co. Ltd, Astellas Pharma Inc., Baxter Limited, AstraZeneca K.K., Shionogi & Co. Ltd. Yoshihiko Saito also belongs to the endowed department (the department of regulatory medicine of blood pressure) sponsored by Merck & Co. Inc. The remaining authors report no conflicts.

Abstract

Objectives

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.

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