Evidence for the treatment of hypertension with combination therapy and the cope trial

高血圧併用療法とCOPE Trial (＜ミニ・レビュー＞小西賞受賞者)

Evidence for the treatment of hypertension with combination therapy and the cope trial

Creators Umemoto Seiji

高血圧患者における心血管イベントの発症予防には降圧目標値を達成することが最も重要であり,そのためには数種類の降圧薬を併用することが多い.われわれは,日本高血圧学会後援のもと,山口大学と協和発酵キリン株式会社の共同研究として,L/T型ジヒドロピリジン系カルシウム拮抗薬ベニジピン4mg/日内服にて降圧目標値を達成できなかった40-85歳の本態性高血圧患者3,293名を対象に,ベニジピンを基礎薬として,アンジオテンシンII受容体拮抗薬,β遮断剤あるいはサイアザイド系類似利尿薬の組み合わせについて心血管疾患発症と降圧目標値達成度を検討したCombination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) TrialをPROBE法にて多施設共同平行群間比較試験としてわが国で初めて実施し,平均3.6年観察した.その結果,ベニジピン+サイアザイド系類似利尿薬の組み合わせは,ベニジピン+β遮断薬の組み合わせよりも脳卒中の発症を有意に抑制した.さらにCOPE Trialのサブ解析として,脳卒中の病型についてTOAST分類を用いてさらに比較検討した結果,患者背景,脳卒中の既往,抗血小板薬/抗凝固薬の投与状況,血圧の推移と降圧目標値達成度のいずれにも3群間で差はなかった.COPE Trialの観察期間中,3群間で脳卒中の発症頻度に差はなかった.一方,脳卒中のハザード比は,ベニジピンとβ遮断剤の併用はサイアザイド系類似利尿薬との併用よりも全脳卒中,脳出血と脳梗塞ともに有意に高値であった.さらに,初発脳出血と一過性脳虚血発作を除く初発脳梗塞の発症頻度も,ベニジピンとβ遮断薬の併用はサイアザイド系類似利尿薬との併用に比べともに有意に高かった.ベニジピンとアンジオテンシンII受容体拮抗薬との併用は,これら2群との間に差はなかった.

It is well-known that the majority of hypertensive patients will require several antihypertensive drugs to reach the target blood pressure. The Combination Therapy of Hypertension to Prevent Cardiovascular Events trial was an investigator-initiated multi-center study with PROBE design, and compared the dihydropyridine T/L-type calcium channel blocker benidipine based therapies with an angiotensin receptor blocker(ARB),a β-blocker(BB),or a thiazide diuretic(TD),and the results suggested that benidipine combined with a BB appeared to be less beneficial in reducing the risk of stroke compared with the benidipine-TD combination. We further evaluated the treatment effects on different stroke subtypes among the three benidipine-based regimens. All stroke events were sub-classified with the TOAST criteria. Although few differences in stroke subtypes were observed among the three treatment groups, multi-adjusted hazard ratios of the incidence of all types of stroke, hemorrhagic stroke and ischemic stroke were significantly higher with the benidipine-BB regimen than with the benidipine-TD regimen. The incidence of both hemorrhagic and ischemic stroke in the benidipine-ARB regimen was not different compared to the other two treatment regimens. This sub-analysis demonstrated that blood pressure-lowering therapy with a benidipine-TD regimen might be beneficial for hypertensive patients to prevent both hemorrhagic and ischemic stroke.

[ISSN]0513-1731

[NCID]AN00243156

[isVersionOf] [NAID]http://ci.nii.ac.jp/naid/40017298870