Amarenco P, et al. Stroke. 2022 Nov, 10.1161/STROKEAHA.122.039728.

 

Introduction

 

2021년 AHA/ASA 가이드라인에서는 atherosclerotic origin의 허혈성 뇌졸중이나 일과성허혈발작 발생 이후에 intensive statin therapy를 통해 LDL cholesterol을 70mg/dL 미만으로 낮출 것을 권고하였다. 관상동맥경화질환 환자에서 statin monotherapy와 비교한 dual therapy (statin+ezetimibe)의 이득을 확인한 연구는 1개밖에 없었고, 뇌졸중 환자에서 dual therapy (statin+ezetimibe)와 statin monotherapy의 효과를 비교 평가한 연구는 없었다.

 

Objectives

 

허혈성 뇌졸중 환자에게 major vascular event의 발생 위험성을 얼마나 낮출 수 있는지 LDL cholesterol target (70mg/dl 미만과 100±10mg/dl)에 따라 dual therapy와 monotherapy의 효과를 확인하고자 한다.

 

Methods

 

● A randomized, event-driven trial. A post hoc analysis of the TST trial (Treat Stroke to Target)

● 대상자: 18세 이상, 3개월이내의 허혈성 뇌졸중 발병, 뇌졸중 이전 mRS 0~3점, TIA, 뇌혈관 또는 관상동맥경화의 증거가 있는 경우.

● Trial design: 1:1 비율로 target LDL 70mg/dL 미만군과, 100±10mg/dl 군으로 배정

● Primary outcome:

- Major cardiovascular event: a composite of adjudicated nonfatal cerebral infarction or stroke of undetermined source, nonfatal myocardial infarction, hospitalization for unstable angina followed by urgent coronary artery revascularization, TIA requiring urgent carotid revascularization, or cardiovascular death including unexplained sudden death.

● Secondary outcome:

- myocardial infarction or urgent coronary revascularization following new symptoms; cerebral infarction or urgent carotid or cerebral artery revascularization following a TIA; cerebral infarction or TIA; any revascularization procedures both urgent and elective (coronary, cerebral or peripheral artery); vascular death; all cause death; cerebral infarction or intracranial hemorrhage; intracranial hemorrhage; newly diagnosed diabetes; composite of primary outcome and intracranial hemorrhage.

● 통계분석: Cox’ proportional hazard model, a multivariable Fine and Gray model

 

Results

● 대상자수: 2010년 3월부터 2018년 12월까지 2873명이 등록되었다. 대조군 (LDL target 100±10mg/dl)은 1430명, 70mg/dL 미만 군은 1430명 배정되었다.

● The achieved LDL cholesterol

 - Dual therapy: 66.2 mg/dL

 - Monotherapy: 64.1 mg/dL

● The primary outcome in lower target group was reduced as compared with the higher target group

 - Major cardiovascular event

   70mg/dL and dual therapy vs. 100±10mg/dL: HR, 0.59 [95% CI, 0.38–0.90]; P=0.016

   70mg/dL and monotherapy vs. 100±10mg/dL: HR, 0.92 [95% CI, 0.70–1.22]; P=0.56

 - no significant increase in intracranial bleeding

● The secondary outcome in lower target group was reduced as compared with the higher target group

 - Cerebral infarction and urgent carotid and cerebral artery revascularization

   70mg/dL and dual therapy vs. 100±10mg/dL: HR, 0.57 [95% CI, 0.33–0.97]; P=0.037

   70mg/dL and monotherapy vs. 100±10mg/dL: HR, 0.93 [95% CI, 0.67–1.29]; P=0.79

 - Primary outcome and intracranial hemorrhage

70mg/dL and dual therapy vs. 100±10mg/dL: HR, 0.62 [95% CI, 0.41–0.94]; P=0.023

   70mg/dL and monotherapy vs. 100±10mg/dL: HR, 0.95 [95% CI, 0.73–1.25]; P=0.74

 

Conclusions

 

죽상동맥경화가 있는 허혈성뇌졸중 환자에게, LDL cholesterol 70mg/dL 미만을 목표로 하는 Dual therapy (statin+ezetimibe)는 100±10mg/dl를 목표로 하는 것에 비해 뇌졸중 발생의 위험성을 낮춘다.