MI後のdarapladib投与はその後のリスクを低下させない（Presentation #2119）

SOLID-TIMI 52: 心筋梗塞後の炎症性酵素阻害はその後のイベントリスクを低下させない
SOLID-TIMI 52: Inhibiting inflammatory enzyme after myocardial infarction does not reduce risk of subsequent event

炎症性酵素リポ蛋白質関連ホスホリパーゼA2を阻害するdarapladibの使用は急性冠症候群（ACS）イベントを来した患者の主要な冠動脈イベント再発のリスクを軽減しなかった。SOLID-TIMI 52（Stabilization Of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction 52）トライアルの主要結果が2014年European Society of Cardiology Congressホットラインセッションで発表され、同時にJAMAオンライン版に掲載された。研究者らはACSで入院後30日以内の患者13,026人を、ガイドライン推奨治療に加え1日1回のdarapladibまたはプラセボ投与を行う群のいずれかにランダムに割り付けた。追跡期間終了時に、スタディの一次エンドポイントである主要な冠動脈イベント（冠動脈疾患死、心臓発作、または心筋虚血に対する緊急冠血行再建術の合計）は、 darapladib群患者6,504人中903人、およびプラセボ群6,522人中910人（3年後の時点で16.3%対15.6%、p=0.93）に発現した。心血管死、心筋梗塞、または脳卒中はdarapladib群824人に対し、プラセボ治療群838人（3年後の時点で15.0%対15.0%、 p=0.78）に発現した。一次エンドポイントまたは総死亡の個々の要素におけるイベント発現率および発現数は治療群間で有意差はなかった。

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In patients who experienced an acute coronary syndrome (ACS) event (such as myocardial infarction or unstable angina), use of the drug darapladib to inhibit the enzyme lipoprotein-associated phospholipase A2 did not reduce the risk of recurrent major coronary events, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress.

A number of epidemiologic studies have shown that higher circulating levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity or mass are associated with an increased risk of coronary events. Darapladib is a Lp-PLA2 inhibitor that reduces Lp-PLA2 activity in plasma and in atherosclerotic plaques, according to background information in the article.

Michelle L. O'Donoghue, M.D., M.P.H., of Brigham and Women's Hospital, Boston, and colleagues randomly assigned 13,026 participants within 30 days of hospitalization with an ACS to either once-daily darapladib or placebo along with guideline-recommended therapy. The study was conducted at 868 sites in 36 countries.

Patients were followed up for a median of 2.5 years. At the end of follow-up, the primary end point of the study, major coronary events (composite of coronary heart disease death, myocardial infarction (MI), or urgent coronary revascularization for myocardial ischemia) had occurred in 903 of 6,504 participants in the darapladib group and 910 of 6,522 participants in the placebo group (16.3 percent vs 15.6 percent at 3 years, hazard ratio [HR], 1.00 [95% CI, 0.91-1.09]; P=0.93). Cardiovascular death, MI, or stroke occurred in 824 darapladib-assigned participants and 838 placebo-treated patients (15.0 percent vs 15.0 percent at 3 years, HR, 0.99 [95% CI, 0.90-1.09]; P=0.78).  There were no significant differences between treatment groups in the incidence and number of events for the individual components of the primary end point.

The rate of all-cause mortality at 3 years was similar between the groups (darapladib, 7.3 percent; placebo, 7.1 percent; HR, 0.94 [95% CI, 0.82-1.08]; P=0.40).

The incidence of any serious adverse event was similar between treatment groups.
The authors conclude that their findings "do not support a strategy of targeted Lp-PLA2 inhibition with darapladib in patients stabilized after an ACS event who are similar to those enrolled into this trial."

This trial was funded by GlaxoSmithKline.