他汀类药物治疗后高密度脂蛋白胆固醇水平反常降低对稳定型心绞痛患者主要不良心血管事件的影响

Impact of Paradoxical Decrease in High-density Lipoprotein Cholesterol Levels After Statin Therapy on Major Adverse Cardiovascular Events in Patients with Stable Angina Pectoris.

作者信息

Hirayama Kenshi, Ota Tomoyuki, Harada Kazuhiro, Shibata Yohei, Tatami Yosuke, Harata Shingo, Kawashima Kazuhiro, Kunimura Ayako, Shimbo Yusaku, Takayama Yohei, Kawamiya Toshiki, Yamamoto Dai, Osugi Naohiro, Suzuki Susumu, Ishii Hideki, Murohara Toyoaki

机构信息

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

Clin Ther. 2017 Feb;39(2):279-287. doi: 10.1016/j.clinthera.2016.12.006. Epub 2016 Dec 26.

DOI:10.1016/j.clinthera.2016.12.006

PMID:28034517

Abstract

PURPOSE

Statin therapy usually increases HDL-C levels. However, a paradoxical decrease in HDL-C levels after statin therapy is often seen in clinical settings. The relationship between a paradoxical decrease in HDL-C levels after statin therapy and adverse cardiovascular events in patients with stable angina pectoris (SAP) is not well understood. The purpose of this study was to analyze the relationship between paradoxical HDL-C decreases after statin therapy and major adverse cardiovascular events (MACEs) in patients undergoing percutaneous coronary intervention (PCI) for SAP.

METHODS

Between January 2006 and March 2015, 867 patients underwent PCI for SAP. Of them, we enrolled 209 patients who were newly started on statin therapy before PCI. We excluded patients who had started statin therapy earlier than 6 months before PCI, patients who had not started statin therapy after PCI, and patients who were diagnosed with acute coronary syndrome. They were divided into 2 groups according to the change in their HDL-C levels between baseline and 6 to 9 months after the index PCI: decreased HDL group after statin treatment (80 patients) and increased HDL group (129 patients). The primary end points were MACEs defined as a composite of all-cause death, nonfatal acute myocardial infarction, and target vessel revascularization (TVR).

FINDINGS

Using Kaplan-Meier analysis, the 7-year event rate for composite MACEs in the decreased HDL group was found to be higher than that for the increased HDL group (38% versus 24%, log-rank P = 0.02). TVR occurred more frequently in the decreased HDL group than in the increased HDL group (32% versus 12%, log-rank P = 0.01). With the use of multivariate analysis, changes in HDL-C levels after statin therapy indicated a significant inverse association with the increased risk of MACEs, (hazard ratio [HR] = 0.94; 95% CI, 0.92-0.97; P < 0.01). The incidence of MACEs was more strongly associated with ΔHDL than with ΔLDL. Moreover, BMS usage also independently predicted MACEs (HR = 2.18; 95% CI, 1.14-4.17; P < 0.01).

IMPLICATIONS

A paradoxical decrease in HDL-C levels after statin therapy might be a risk factor for MACEs, especially TVR, in patients with SAP.

摘要

目的

他汀类药物治疗通常会升高高密度脂蛋白胆固醇（HDL-C）水平。然而，在临床环境中，他汀类药物治疗后HDL-C水平出现反常下降的情况却屡见不鲜。他汀类药物治疗后HDL-C水平的反常下降与稳定型心绞痛（SAP）患者不良心血管事件之间的关系尚不清楚。本研究旨在分析接受经皮冠状动脉介入治疗（PCI）的SAP患者中，他汀类药物治疗后HDL-C反常下降与主要不良心血管事件（MACE）之间的关系。

方法

2006年1月至2015年3月期间，867例患者因SAP接受了PCI治疗。其中，我们纳入了209例在PCI术前新开始他汀类药物治疗的患者。我们排除了在PCI术前6个月之前就开始他汀类药物治疗的患者、PCI术后未开始他汀类药物治疗的患者以及被诊断为急性冠状动脉综合征的患者。根据PCI术后6至9个月与基线相比HDL-C水平的变化，将他们分为两组：他汀治疗后HDL降低组（80例患者）和HDL升高组（129例患者）。主要终点是定义为全因死亡、非致命性急性心肌梗死和靶血管血运重建（TVR）的复合MACE。

研究结果

采用Kaplan-Meier分析，发现HDL降低组复合MACE的7年事件发生率高于HDL升高组（38%对24%，对数秩检验P = 0.02）。HDL降低组TVR的发生频率高于HDL升高组（32%对12%，对数秩检验P = 0.01）。通过多变量分析，他汀类药物治疗后HDL-C水平的变化表明与MACE风险增加存在显著负相关（风险比[HR]=0.94；95%可信区间，0.92 - 0.97；P < 0.01）。MACE的发生率与HDL的变化比与低密度脂蛋白（LDL）的变化更密切相关。此外，使用裸金属支架（BMS）也独立预测了MACE（HR = 2.18；95%可信区间，1.14 - 4.17；P < 0.01）。