ACS治療において抗凝固薬はリスクを低下させる（AHA Abstract # 26520）

ATLAS ACS 2-TIMI 51：急性冠症候群患者において低用量rivaroxabanは死亡、心筋梗塞および脳卒中リスクを低下させた
ATLAS ACS 2-TIMI 51: Low-dose rivaroxaban lowered risk of death, myocardial infarction and stroke in acute coronary syndrome patients
標準的な薬物治療に経口抗凝固薬rivaroxabanを追加することにより、急性冠症候群（ACS）患者の死亡、心筋梗塞（MI）、脳卒中のリスクが低下したとのlate-breaking research の結果が2011年American Heart Association学会で発表され、同時にNew England Journal of Medicineに掲載された。急性冠症候群患者の心血管イベント軽減のための標準治療への抗Xa療法の追加 ―心筋梗塞に対する血栓溶解療法 51トライアル（Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 Trial：ATLAS ACS 2-TIMI 51）では、ACS患者15,526人をrivaroxaban 2.5mg（5,174人）、5.0mg（5,176人）、またはプラセボ（5,176人）を平均13ヵ月投与する群に無作為に割り付けた。両用量のrivaroxaban群を合わせた群ではプラセボ群と比較し、心血管死亡、脳卒中またはMIリスクが16%と有意に低下した。総死亡を含めた死亡リスクはrivaroxabanを追加することにより30%以上低下した。ステント血栓はrivaroxabanを内服した患者においてこれを内服しなかった患者と比較し、31%少なかった。用量の点では、低用量群において結果が最も良好であった。Rivaroxaban群では重大な出血および脳内出血が3倍多かったが、致死的な出血は有意に多くはなかった。
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Added to standard medical treatment, the oral anticoagulant rivaroxaban lowered overall risk of mortality, myocardial infarction and stroke in acute coronary syndrome patients, according to late-breaking research presented at the American Heart Association's Scientific Sessions 2011 and simultaneously published in the New England Journal of Medicine.

"Despite our best efforts at treatment following a recent heart attack or unstable angina, patients still face a 10 percent or higher risk of a repeat heart attack, stroke or death one year later," said C. Michael Gibson, M.D., senior investigator of the TIMI Study Group, Harvard Medical School, and the Principal Investigator in the ATLAS ACS studies of rivaroxaban for this indication.

"We know that people with a heart attack or unstable angina make too much thrombin, an enzyme that forms clots. We looked at whether reducing the production of thrombin with rivaroxaban reduces the risk of death, stroke or heart attack."

Researchers analyzed more than 15,000 people hospitalized with a recent myocardial infarction or unstable angina in the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 Trial (ATLAS ACS 2-TIMI 51). Study participants were randomized to receive either standard care along with rivaroxaban [2.5 mg rivaroxaban (n=5,174), 5.0 mg rivaroxaban (n=5,176)] or standard care with placebo (n=5,176).

Researchers followed these patients for a mean of 13 months and found:

  • Those who took rivaroxaban had a 16 percent reduced risk of cardiovascular death, stroke or heart attack compared to patients who didn't.
  • The risk of death, including all causes of death, was reduced more than 30 percent with the addition of rivaroxaban.
  • Stent thrombosis was reduced by 31 percent in patients taking rivaroxaban compared to patients who didn't.
  • As with other types of anticoagulants, more internal bleeding occurred among those who took rivaroxaban than those who took placebo and the increase in TIMI major bleeding was significant. However, there was no increase in fatal bleeding.

In terms of the individual doses, the lower dose showed the best results.

Rivaroxaban and other new oral anticoagulants have demonstrated the ability to reduce strokes in patients with atrial fibrillation, but their use in patients with acute coronary syndrome has had mixed results. Because these patients are often on other anticoagulants, the bleeding risk has been very high.

"Our findings are important because blocking the production of thrombin is an important new way to improve acute coronary syndrome patients' long-term risk of death, stroke and heart attack after being hospitalized with an acute coronary syndrome," Gibson said.

The authors conclude that very low dose rivaroxaban poses an effective treatment to minimize cardiovascular events in patients with acute coronary syndromes.

Co-authors are Eugene Braunwald, M.D., and Jessica Mega, M.P.H., M.D.

Johnson and Johnson and Bayer HealthCare funded the study.