AIM HIGH: Niacin Plus Statin to Prevent Vascular Events

描述(由申请人提供)： AIM-HIGH是一项多中心对照临床试验，旨在测试在同等水平的治疗中低密度脂蛋白(LDL-C)水平下，烟酸缓释剂加辛伐他汀联合用药是否优于单用辛伐他汀，以延迟动脉粥样硬化性血脂异常患者在4年中位随访期内首次发生重大心血管疾病的时间。先前的临床试验发现，使用他汀类单一疗法仅可降低25%-35%的心血管风险(即事件发生率为安慰剂率的2/3至3/4)。这项拟议的研究需要确认他汀类和烟酸联合治疗是否将提供更显著(50%)的心血管事件减少，该联合治疗旨在针对除低密度脂蛋白-C之外的更广泛的血脂异常因素。流行病学研究证实致动脉粥样硬化性血脂异常的高发及其对心血管事件发生率的影响。初步临床试验表明，以这些因素为靶点进行降脂治疗将减少心血管事件。这项拟议的研究将纳入45岁的男性和女性，因为他们患有心血管疾病，并伴有代谢综合征的两种血脂紊乱因素--低高密度脂蛋白-胆固醇(HDL-C)[=40 mg/dl]和高甘油三酯(TG)[=150 mg/dl]。这项拟议的研究专门针对心血管死亡、非致命性心肌梗死(ML)、非出血性中风或因有客观缺血证据(肌钙蛋白阳性或ST段偏移)的高风险急性冠脉综合征住院的主要综合临床终点测试这一假设。次要终点是心血管死亡、非致命性ML或非出血性卒中的组合。3300名患者样本将在美国和加拿大的54个中心招募，主要终点的功率为90%，与他汀类药物单一疗法相比，以上三个终点的风险降低29%的功率最高可达85%。综上所述，他汀类药物对高密度脂蛋白胆固醇水平影响不大，仅适度降低心血管风险。AIM-HIGH旨在证实使用他汀类药物加烟酸的“完全”脂肪疗法有更大的益处。

DESCRIPTION (provided by applicant): AIM-HIGH is a multicenter controlled clinical trial designed to test whether the drug combination extended release niacin plus simvastatin is superior to simvastatin alone, at comparable levels of in-treatment LDLcholesterol (LDL-C), for delaying the time to a first major cardiovascular (CV) disease outcome over a 4-year median follow-up in patients with atherogenic dyslipidemia. Prior clinical trials have found only 25-35% CV risk reduction using statin monotherapy (i.e., event rate 2/3 to 3/4 of placebo rate). The proposed study is needed to confirm whether statin-niacin combination therapy, designed to target a wider spectrum of dyslipidemic factors in addition to LDL-C, will provide a more substantial (>50%) reduction of CV events. Epidemiologic studies confirm the high prevalance of atherogenic dyslipidemia and its impact on CV event rates. Preliminary clinical trials suggest that targeting these factors with dylipidemic therapy will reduce CV events. The proposed study will enroll men and women >45 years old at high risk of recurrent CV events by virtue of having established CV disease together with the two dyslipidemic elements of metabolic syndrome - low HDL-cholesterol (HDL-C) [<=40 mg/dl] and high triglycerides (TG) [>=150 mg/dl]. The proposed study specifically aims to test this hypothesis for the primary composite clinical endpoint of CV death, nonfatal myocardial infarction (Ml), non-hemorrhagic stroke, or hospitalization for high-risk acute coronary syndrome with objective evidence of ischemia (troponin-positive or ST-segment deviation). A secondary endpoint is the composite of CV death, non-fatal Ml, or non-hemorrhagic stroke. The 3300-patient sample, to be recruited in 54 centers in US and Canada, will have >90% power for the primary endpoint, and up to 85% power to confirm a 29% risk reduction, relative to statin monotherapy, for the triple endpoint above. In summary, statins have little effect on HDL-C orTG, and only moderately reduce CV risk. AIM-HIGH is designed to confirm a substantially greater benefit from "complete" lipid therapy using statins plus niacin.