英国伦敦帝国理工学院Kausik K. Ray小组在研究中取得进展。他们探讨了阿帕他隆联合标准疗法治疗近期急性冠脉综合征和2型糖尿病患者对主要心血管不良事件的影响。相关论文于2020年3月27日发表在《美国医学会杂志》上。

溴结构域和末端外蛋白是基因转录的表观遗传调控因子。阿帕他隆是一种针对溴结构域2的选择性溴结构域和末端蛋白抑制剂，据推测对动脉粥样硬化相关途径有潜在的有利影响。汇总的临床2期数据表明其对临床结局有益。

为了探讨阿帕他隆是否能减少主要心血管不良事件，研究组在13个国家/地区的190个地点进行了一项随机、双盲、安慰剂对照试验。2015年11月11日至2018年7月4日，研究组招募了2425名7-90天内发生急性冠状动脉综合征、2型糖尿病且高密度脂蛋白胆固醇水平低的患者，在标准治疗的基础上，将其按1：1随机分组，其中1215例口服阿帕他隆，1210例口服安慰剂。主要结局是首次发生心血管死亡、非致命性心肌梗死或中风。

2425名患者的平均年龄为62岁，女性占25.6%，2320名纳入最终分析。中位随访26.5个月后，共发生274例主要结局，其中阿帕他隆组有125例，占10.3%；安慰剂组149例，占12.4%，差异不显著。阿帕他隆组有2.9%的患者肝酶水平升高，因不良反应而停药者占9.4%；安慰剂组则分别为0.9%和5.7%。

总之，对于近期发生急性冠状动脉综合征、2型糖尿病且高密度脂蛋白胆固醇水平低的患者，标准治疗添加阿帕他隆并不能显著降低严重不良心血管事件的风险。

附：英文原文

Title: Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial

Author: Kausik K. Ray, Stephen J. Nicholls, Kevin A. Buhr, Henry N. Ginsberg, Jan O. Johansson, Kamyar Kalantar-Zadeh, Ewelina Kulikowski, Peter P. Toth, Norman Wong, Michael Sweeney, Gregory G. Schwartz

Issue&Volume: 2020-03-27

Abstract: Abstract

Importance  Bromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes.

Objective  To test whether apabetalone significantly reduces major adverse cardiovascular events.

Design, Setting, and Participants  A randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019.

Interventions  Patients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n=1215), or matching placebo (n=1210) in addition to standard care.

Main Outcomes and Measures  The primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke.

Results  Among 2425 patients who were randomized (mean age, 62 years; 618 women [25.6%]), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalone-treated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 [95% CI, 0.65-1.04]; P=.11). More patients allocated to apabetalone than placebo discontinued study drug (114 [9.4%] vs 69 [5.7%]) for reasons including elevations of liver enzyme levels (35 [2.9%] vs 11 [0.9%]).

Conclusions and Relevance  Among patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events.

DOI: 10.1001/jama.2020.3308

Source: https://jamanetwork.com/journals/jama/fullarticle/2763951