贝匹地酸用于他汀类药物不耐受患者的心血管事件一级预防。
Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients.
机构信息
Cleveland Clinic, Cleveland, Ohio.
Victorian Heart Institute, Monash University, Melbourne, Australia.
出版信息
JAMA. 2023 Jul 11;330(2):131-140. doi: 10.1001/jama.2023.9696.
IMPORTANCE
The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.
OBJECTIVE
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.
INTERVENTIONS
Participants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106).
MAIN OUTCOME MEASURES
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.
RESULTS
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.
CONCLUSIONS
In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02993406.
重要性
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。
目的
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。
干预措施
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）。
主要终点测量
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。
结果
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。
结论
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。
试验注册
ClinicalTrials.gov 标识符：NCT02993406。
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