P642What is the most important residual risk after achievement of appropriate low-density lipoprotein cholesterol lowering therapy in secondary prevention of Japanese patients?
Authors: Endo A , Okada T , Kagawa Y , Sato H , Morita Y , Pak M , Ouchi T , Watanabe N , Yamaguchi K , Yoshitomi H , Tanabe K 
Published: October 2019

Abstract

Background
In secondary prevention of coronary artery disease, target value of low-density lipoprotein cholesterol (LDL-C) <100mg/dL with using statins is recommended as standard therapy in Japanese guideline. However, impact of residual risks after achievement of standard LDL-C lowering therapy was not fully examined. Furthermore, there is little information whether more strict management of LDL-C lowering is effective to prevent long-term cardiovascular events than standard management.

Purpose
The purpose of this study was to evaluate the relationship between residual risks after achievement of standard LDL-C lowering therapy and long-term coronary events in secondary prevention of Japanese patients.

Methods
From January 2007 to August 2018, 333 patients with previous percutaneous coronary intervention underwent late coronary angiography to examine recurrence of cardiac ischemia beyond the early phase of restenosis. We defined appropriate LDL-C lowering therapy as achieved LDL-C <100mg/dL with using statins. Patients whose achieved LDL-C was <100mg/dL with using statins were classified as Appropriate-group (n=139), and patients who were not using statins or whose achieved LDL-C was ≥100mg/dL were classified as Inappropriate-group (n=194). Endpoints of the study were recurrence of cardiac ischemia as acute coronary syndrome (recurrence-ACS) and any late coronary revascularization.

Results
During average 7.1 years follow-up, 195 patients (59%) underwent any late coronary revascularization. In 91 of those patients, clinical presentation of recurrence-ACS was observed. Kaplan-Meier curve analysis revealed that the incidence of recurrence-ACS and any late coronary revascularization were significantly lower in Appropriate-group than in Inappropriate-group (p=0.017 and p<0.001, respectively). In Appropriate-group, recurrence-ACS was significantly lower in patients with achieved LDL-C <70mg/dL than in those with LDL-C 70 to <100mg/dL (p=0.042), however, any late revascularization was not different between the two groups. On the other hand, in Inappropriate-group, recurrence-ACS was significantly lower in patients with using statins than in those without using statins (p=0.038), and any late revascularization was less frequent in patients with achieved LDL-C <100mg/dL than in those with LDL-C ≥100mg/dL (p=0.035). Moreover, multivariate analysis identified that only LDL-C was an independent predictor of recurrence-ACS in Appropriate-group (HR: 1.047, p=0.006), in contrast, LDL-C (HR: 1.008, p=0.020), using statins (HR: 0.555, p=0.034) and triglyceride (HR: 1.003, p=0.038) were independent predictors of recurrence-ACS in Inappropriate-group.

Conclusions
LDL-C was the most important residual risk of recurrence-ACS even after recommended standard therapy has been achieved. More strict management of LDL-C targeting to <70mg/dL should be considered in secondary prevention of Japanese patients.