N Engl J Med. 2014 Jul 17;371(3):203-12. doi: 10.1056/NEJMoa1300955.
Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) cholesterol level, but its clinical efficacy and safety are uncertain.
After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization).
During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher than the levels in those assigned to placebo. Assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events (13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29). Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; P<0.001) and with an increased incidence of diabetes diagnoses (absolute excess, 1.3 percentage points; P<0.001), as well as increases in serious adverse events associated with the gastrointestinal system (absolute excess, 1.0 percentage point; P<0.001), musculoskeletal system (absolute excess, 0.7 percentage points; P<0.001), skin (absolute excess, 0.3 percentage points; P=0.003), and unexpectedly, infection (absolute excess, 1.4 percentage points; P<0.001) and bleeding (absolute excess, 0.7 percentage points; P<0.001).
Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.).
尽管使用他汀类药物有效降低了低密度脂蛋白胆固醇（LDL-C）水平，但有血管疾病证据的患者仍存在随后发生血管事件的风险增加。烟酸可降低 LDL-C 水平并升高高密度脂蛋白胆固醇（HDL-C）水平，但它的临床疗效和安全性尚不确定。
在标准化基于他汀类药物的 LDL-C 降低治疗和确定参与者能够在无临床显著不良反应的情况下服用缓释烟酸的预随机导入期后，我们将 25673 名患有血管疾病的成年人随机分配接受 2g 缓释烟酸和 40mg 拉罗匹坦或匹配的安慰剂，每日一次。主要结局是首次主要血管事件（非致死性心肌梗死、因冠状动脉原因死亡、卒中和动脉血运重建）。
在中位数为 3.9 年的随访期间，与安慰剂组相比，接受缓释烟酸-拉罗匹坦治疗的患者 LDL-C 水平平均降低 10mg/dL（0.25mmol/L，以中心实验室测量为准），HDL-C 水平平均升高 6mg/dL（0.16mmol/L）。与安慰剂组相比，缓释烟酸-拉罗匹坦组的主要血管事件发生率无显著差异（分别为 13.2%和 13.7%的患者发生事件；率比为 0.96；95%置信区间[CI]为 0.90 至 1.03；P=0.29）。缓释烟酸-拉罗匹坦与糖尿病控制的严重紊乱发生率增加相关（与安慰剂相比，绝对差异为 3.7 个百分点；P<0.001），糖尿病诊断发生率增加（绝对差异为 1.3 个百分点；P<0.001），以及与胃肠道系统（绝对差异为 1.0 个百分点；P<0.001）、肌肉骨骼系统（绝对差异为 0.7 个百分点；P<0.001）、皮肤（绝对差异为 0.3 个百分点；P=0.003）以及意外的感染（绝对差异为 1.4 个百分点；P<0.001）和出血（绝对差异为 0.7 个百分点；P<0.001）相关的严重不良事件发生率增加。
在患有动脉粥样硬化性血管疾病的患者中，缓释烟酸-拉罗匹坦联合他汀类药物降低 LDL-C 治疗并未显著降低主要血管事件的风险，但增加了严重不良事件的风险。（由默克公司和其他公司资助；HPS2-THRIVE 临床试验.gov 编号，NCT00461630。）
