治験薬は心血管イベント再発リスクを低下させなかった（LBCT 4/Abstract: 19610）

VISTA-16：Varespladibが心筋梗塞リスク上昇と関連していることが示されたためトライアルは早期に中止された
VISTA-16: Trial halted early after varespladib is linked with increased risk of myocardial infarction
分泌性ホスホリパーゼA2阻害薬varespladibは、急性冠症候群患者の再発性心血管イベントを予防せず心筋梗塞（MI）リスク上昇と関連するとの late-breaking clinical trialの結果が2013年American Heart Associationで発表され、同時にJAMAオンライン版に掲載された。これらの結果から大規模臨床試験VISTA-16の結論が早期に得られた。研究者らは、17か国362施設の心筋虚血症状を有する40歳以上の患者5,000人超を調査した。彼らは患者を、毎日500mgのvarespladibまたはプラセボを16週間投与される群に無作為に割り付けた。全ての患者が確立された急性冠症候群治療薬も投与された。治療は患者が症状を有し病院に到着してから96時間以内に開始された。スタディが早期に中止された時点で、varespladib群患者の6.1%がMI、他の心血管合併症、または死亡を含む再発性イベントを発現し、それと比較しプラセボ 群では5.1%であった。Varespladibを投与された患者はプラセボを投与された患者よりもMI再発率が有意に高かった（3.4%対2.2%）。
Full Text

The experimental drug varespladib, a secretory phospholipase A2 inhibitor, doesn't prevent cardiovascular events from recurring and is linked to increased risk of myocardial infarction (MI) in patients with acute coronary syndrome (ACS), according to a late-breaking clinical trial presented at the American Heart Association's Scientific Sessions 2013 and simultaneously published online in JAMA.

These findings led to the early conclusion of VISTA-16, a large clinical trial examining whether the drug, varespladib, a secretory phospholipase A2 inhibitor, could prevent future events among patients hospitalized with ACS.

Researchers studied more than 5,000 patients, 40 years and older with symptoms of decreased blood flow to the heart at 362 sites in 17 countries in May 2010-March 2012. They randomly assigned patients to receive 500 milligrams of varespladib or placebo daily for 16 weeks.

All patients also received established medications for treating blocked blood vessels to the heart. Treatment began within 96 hours of patients' arrival at the hospital with symptoms.

At the study's early termination in March 2012, 6.1 percent of patients in the varespladib group had recurrent events including heart attacks, other heart complication, or death, as compared to 5.1 percent among the placebo group.

Patients who received varespladib were significantly more likely to have a recurrent heart MI (3.4 percent) than those who received placebo (2.2 percent).

"Varespladib was not associated with improvement of severe heart disease and resulted in a greater rate of heart attacks," said Stephen Nicholls, M.D., Ph.D., the study's lead author and deputy director of the South Australian Health and Medical Research Institute.

Previous laboratory studies had revealed that varespladib inhibits tissue inflammation — possibly preventing heart events related to a decrease in blood and oxygen flow to the heart.

"That theory didn't play out in our study," said Nicholls, professor of cardiology at the University of Adelaide and consultant cardiologist at the Royal Adelaide Hospital in Australia. "In fact, our results suggest the drug could be more harmful for these patients."

Co-authors are J.J. Kastelein, M.D., Ph.D.; Danielle Brennan, M.S. and Gregory G. Schwartz, Ph.D.

Anthera Pharmaceuticals funded the study.