胃腸障害は抗血小板薬の重大な問題になっている。プロトンポンプ阻害剤PPIsは、この合併症のリスクを減少させると信じられていますが、抗血小板療法をしている患者へのランダム化比較試験は実施されていませんでした。最近では、PPIsがクロピドグレルの効果を減弱させるという報告もあります。
N Engl J Med 2010;363:1909-17.
Clopidogrel with or without Omeprazole in Coronary Artery Disease
・クロピドグレルで治療をしている患者に、オメプラゾール、もしくはプラセボを投与
・プライマリエンドポイントは、消化器側と循環器側の両方に設定
・胃腸障害のイベントは、180日間の投与で、オメプラゾール群1.1%、プラセボ群2.9%（ハザード比0.34、信頼区間0.18 to 0.63; P<0.001）
・循環器のイベントは、オメプラゾール4.9%、プラセボ5.7%（ハザード比0.99; 95% CI, 0.68 to 1.44; P=0.96）
Background
Gastrointestinal complications are an important problem of antithrombotic therapy. Proton-pump inhibitors (PPIs) are believed to decrease the risk of such complica- tions, though no randomized trial has proved this in patients receiving dual anti- platelet therapy. Recently, concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel.
Methods
We randomly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo, in addition to aspirin. The primary gastrointestinal end point was a composite of overt or oc- cult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or per- foration. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke. The trial was terminated prematurely when the sponsor lost financing.
Results
We planned to enroll about 5000 patients; a total of 3873 were randomly assigned and 3761 were included in analyses. In all, 51 patients had a gastrointestinal event; the event rate was 1.1% with omeprazole and 2.9% with placebo at 180 days (hazard ratio with omeprazole, 0.34, 95% confidence interval [CI], 0.18 to 0.63; P<0.001). The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo (hazard ratio, 0.13; 95% CI, 0.03 to 0.56; P=0.001). A total of 109 patients had a cardiovascular event, with event rates of 4.9% with omepra- zole and 5.7% with placebo (hazard ratio with omeprazole, 0.99; 95% CI, 0.68 to 1.44; P=0.96); high-risk subgroups did not show significant heterogeneity. The two groups did not differ significantly in the rate of serious adverse events, though the risk of diarrhea was increased with omeprazole.
Conclusions
Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI. (Fund- ed by Cogentus Pharmaceuticals
気づき）
・消化器イベントは減少するも、オメプラゾールの併用で本来の循環器イベントの減少が見込めない＝クロピドグレルを服用しても、意味がないということか？
・他のPPIsでは、どうか？（クロピドグレルの作用を邪魔しない選択はあるのか？）
・他の重要な副作用に相違がないことは、ラッキー
これから）２月のＥＢＭ中野は、クロピドグレル＋PPIsのシナリオでした。この論文は参加者が検索をして選んだ２本の論文のうちの１つ。和訳の分担がまわってきましたので、アブストラクトをまず読みました。クロピドグレル＋オメプラゾールって結構処方あると思うのですが・・・
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