Ezetimibe Added to Statin Therapy
after Acute Coronary Syndromes
IMPROVE-IT試験
DOI: 10.1056/NEJMoa1410489 online first
double-blind, randomized, placebo-controlled trial
Patients:
Men and women who were at least 50 years of age were eligible for inclusion if they had been hospitalized within the preceding 10 days for an acute coronary syndrome (an acute myocardial infarction, with or without ST-segment elevation on electrocardiography, or high-risk unstable angina22-24; detailed definitions are provided in the Supplementary Appendix). Patients were required to have an LDL cholesterol level of 50 mg per deciliter (1.3 mmol per liter) or higher. For participants who were not receiving long-term lipid-lowering therapy, the maximum LDL choles- terol level for enrollment was 125 mg per deciliter (3.2 mmol per liter); for participants who were receiving lipid-lowering therapy, the maximum level was 100 mg per deciliter.
50歳以上のACS患者．LDLは50-125mg/dl，あるいは既に脂質異常症の治療されている患者では100mg/dl以下．
Intervention:
combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin–ezetimibe)
comparison:
simvastatin (40 mg)
Outcomes:
The primary efficacy end point was a composite of death from cardiovascular disease, a major coronary event (nonfatal myocardial infarction, documented unstable angina requiring hospital admission, or coronary revascularization occur- ring at least 30 days after randomization), or nonfatal stroke, assessed from the time of ran- domization until the first occurrence of one of the events.
心血管系イベントのcomposite
その他，secondory outcomes3つ，それぞれの項目も．
ランダム化
本文には記載がいまいち．まぁでもプラセボではある．
目隠し
評価者は何もしらないと記載あり．その他は記載あまりないが，double blind
評価
ITT解析
その他の治療介入
アスピリン，プラビックス，β-blocker，ACE-I/ARBは同じ
サンプルサイズ
5250 events would be required to give the study 90% power to detect a 9.375% lower relative risk for the primary end point with simvastatin–ezetimibe than with simvastatin monotherapy.
β=0.9
RRの減少は9.375%と見積もる
adjustment of the level of signifi- cance to account for the three interim analyses was determined by the Lan–DeMets approxima- tion of the O’Brien–Fleming boundaries for group sequential testing, with a final two-sided P value for significance of 0.0394 or less.
interim analysisに伴いα=0.0394に下げている．
A nominal P value of 0.05 or less without adjustment for multiple testing was used for other end points.
primary以外はα=0.05
Results
Primary outcomeは，34.7％-->32.7％へ減少．p=0.016 NNT=50
secondary outcomeも概ね減少傾向．
それぞれのイベントでは，主に心臓のイベントが減っている．
subgroup analysisでは75歳以上で特に効果が高かった．
副作用は差なし
使うか．
200円/日，73000円/年
ACS患者においては使ってもよいだろう．けれど，ゼチーアのいままでの経緯を考えると本当なのか？ま，間違っても一次予防に使うものではない．
もちろんFundingはメルク社．