Cleveland Clinic, Cleveland, Ohio.
Victorian Heart Institute, Monash University, Melbourne, Australia.
JAMA. 2023 Jul 11;330(2):131-140. doi: 10.1001/jama.2023.9696.
The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.
To determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients.
DESIGN, SETTING, AND PARTICIPANTS: This masked, randomized clinical trial enrolled 13 970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients.
Participants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106).
The primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.
Mean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84]; P < .001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels.
In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events.
ClinicalTrials.gov Identifier: NCT02993406.
贝匹地酸对无既往心血管事件（一级预防）的他汀类药物不耐受患者的心血管结局的影响尚未完全描述。
确定贝匹地酸对一级预防患者心血管结局的影响。
设计、地点和参与者：这项双盲、随机临床试验纳入了 13970 名他汀类药物不耐受患者（2016 年 12 月至 2019 年 8 月在 32 个国家的 1250 个中心入组），其中包括 4206 名一级预防患者。
参与者被随机分配接受口服贝匹地酸，每日 180 毫克（n=2100）或匹配安慰剂（n=2106）。
主要疗效测量指标是从随机分组到任何心血管死亡、非致死性心肌梗死（MI）、非致死性卒中和冠状动脉血运重建的复合终点的首次发生时间。
平均参与者年龄为 68 岁，59%为女性，66%患有糖尿病。与安慰剂相比，贝匹地酸使平均基线为 142.2mg/dL 的低密度脂蛋白胆固醇水平降低了 30.2mg/dL（21.3%），使高敏 C 反应蛋白水平降低了 0.56mg/L（21.5%），中位基线水平为 2.4mg/L。中位随访 39.9 个月与主要终点的显著风险降低相关（111 例事件[5.3%]与 161 例事件[7.6%]；调整后的危险比[HR]，0.70[95%CI，0.55-0.89]；P=0.002）和关键次要终点，包括心血管死亡、MI 或卒中的复合终点（83 例事件[4.0%]与 134 例事件[6.4%]；HR，0.64[95%CI，0.48-0.84]；P<0.001）；MI（29 例事件[1.4%]与 47 例事件[2.2%]；HR，0.61[95%CI，0.39-0.98]）；心血管死亡（37 例事件[1.8%]与 65 例事件[3.1%]；HR，0.61[95%CI，0.41-0.92]）和全因死亡率（75 例事件[3.6%]与 109 例事件[5.2%]；HR，0.73[95%CI，0.54-0.98]）。对卒中和冠状动脉血运重建没有显著影响。贝匹地酸的不良反应包括痛风（2.6%比 2.0%）、胆石症（2.5%比 1.1%）的发生率较高，以及血清肌酐、尿酸和肝酶水平升高。
在高危一级预防患者亚组中，贝匹地酸治疗与主要心血管事件减少相关。
ClinicalTrials.gov 标识符：NCT02993406。
