BACKGROUND Cardiac allograft vasculopathy is characterized by increased coronary intimal thickness and is a leading cause of death in heart transplant (HTx) recipients despite the routine use of statins. The experience with inhibitors of proprotein convertase subtilisin-kexin type 9 in HTx recipients is limited. Our hypothesis was that lowering cholesterol with the proprotein convertase subtilisin-kexin type 9inhibitor evolocumab would reduce coronary intimal thickness in these patients without compromising safety. OBJECTIVES This double blind, randomized trial was conducted to test whether evolocumab reduces the burden of cardiac allograft vasculopathy. METHODS Patients who had received a cardiac allograft at one of the Nordic transplant centers within the prior 4 to 8 weeks were randomized to monthly subcutaneous injections of evolocumab 420 mg or matching placebo. The primary endpoint was the baseline-adjusted maximal intimal thickness as measured by intracoronary ultrasound after 12 months' treatment. RESULTS The trial enrolled 128 patients between June 2019 and May 2022. Matched pairs of coronary ultrasound images were available for 56 patients assigned to evolocumab and 54 patients assigned to placebo. At 12 months, the adjusted mean difference in the maximal intimal thickness between the 2 arms was 0.017 mm (95% CI: -0.006 to 0.040; P = 0.14). The mean reduction in low-density lipoprotein cholesterol with evolocumab compared with placebo was 1.11 mmol/L (95% CI: 0.86-1.37 mmol/L). The use of evolocumab was not associated with an increase in adverse events. CONCLUSIONS Twelve months of treatment with evolocumab substantially reduced low-density lipoprotein cholesterol but did not reduce maximal coronary intimal thickness in HTx recipients. (Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-novo Heart Transplant Recipients [EVOLVD]; NCT03734211).

中文翻译：

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使用 Evolocumab 降低胆固醇治疗心脏移植受者心脏同种异体移植血管病变的随机试验。


背景心脏同种异体移植血管病变的特征是冠状动脉内膜厚度增加，并且是心脏移植（HTx）接受者死亡的主要原因，尽管常规使用他汀类药物。在 HTx 接受者中使用前蛋白转化酶枯草杆菌蛋白酶-kexin 9 型抑制剂的经验有限。我们的假设是，用前蛋白转化酶枯草杆菌蛋白酶-kexin 9 型抑制剂 evolocumab 降低胆固醇，可以在不影响安全性的情况下减少这些患者的冠状动脉内膜厚度。目的 这项双盲、随机试验旨在测试 evolocumab 是否可以减轻心脏同种异体移植血管病变的负担。方法 4 至 8 周内在北欧移植中心之一接受同种异体心脏移植的患者被随机分配，每月皮下注射 evolocumab 420 mg 或匹配的安慰剂。主要终点是治疗 12 个月后通过冠状动脉内超声测量的基线调整最大内膜厚度。结果 该试验在 2019 年 6 月至 2022 年 5 月期间入组了 128 名患者。56 名接受 evolocumab 治疗的患者和 54 名接受安慰剂的患者有匹配的冠状动脉超声图像对。 12 个月时，2 臂之间最大内膜厚度的调整后平均差异为 0.017 毫米（95% CI：-0.006 至 0.040；P = 0.14）。与安慰剂相比，evolocumab 低密度脂蛋白胆固醇的平均降低量为 1.11 mmol/L（95% CI：0.86-1.37 mmol/L）。使用 evolocumab 与不良事件的增加无关。结论 使用 evolocumab 治疗 12 个月显着降低了 HTx 受者的低密度脂蛋白胆固醇，但没有降低最大冠状动脉内膜厚度。 （使用 EVOLocumab 降低胆固醇以预防新心脏移植受者的心脏同种异体移植血管病变 [EVOLVD]；NCT03734211）。