P5320Reduction in high-sensitivity C-reactive protein by pitavastatin was associated with improved outcomes in Japanese patients with stable coronary artery disease: results from REAL-CAD study
Authors: Iwata H , Iimuro S , Inoue A , Miyauchi K , Taguchi I , Hiro T , Nakagawa Y , Ozaki Y , Ohashi Y , Daida H , Shimokawa H , Kimura T , Nagai R 
Published: October 2019

Abstract

Background
The effect of statins on lowering high sensitivity C-reactive protein (hs-CRP) as well as low density lipoprotein cholesterol (LDL-C) has been associated with reduced risk for cardiovascular events in patients with elevated hs-CRP. However, it remains unclear whether this statin effect applies to low-risk patients with stable coronary artery disease (CAD). In this pre-specified sub-study within the REAL-CAD trial, we explored the association between achieved LDL-C/hs-CRP levels and cardiovascular events in Japanese patients with stable CAD who were treated with pitavastatin 1 mg or 4 mg/day.

Methods
The REAL-CAD trial randomly allocated 13,054 patients with stable CAD to pitavastatin 1 mg or 4 mg/day. LDL-C and hs-CRP were measured at baseline and at 6 months after randomization. We excluded those patients without 6-month data and those with endpoint events before 6 months (N=1915). The primary endpoint of the study was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. Outcomes were assessed by landmark analysis beyond 6 months among 4 groups that were configured based on LDL-C (median) and hs-CRP (median) targets: achieving neither target, achieving LDL-C target only, achieving hs-CRP target only, and achieving both targets. Data were adjusted for baseline characteristics including age, gender, diabetes and baseline values of LDL-C and hs-CRP.

Results
Median LDL-C and hs-CRP levels were 88 mg/dL and 0.52 mg/L at baseline and 80 mg/dL and 0.48 mg/L after 6 months, respectively. There was no correlation between the change in LDL-C and hs-CRP levels from baseline to 6 months (correlation coefficient: 0.009, P=0.331). Of the 11,677 patients included in the study, 25.1% (N=2799) achieved both LDL-C and hs-CRP targets, 25.3% (N=2282) met neither target, 24.8% (N=2765) met only the hs-CRP target, and 24.7% (N=2753) met only the LDL-C target. Risk of primary endpoint occurrence was significantly lower in those achieving either or both targets than in those meeting neither target (Figure A). In the subgroup analysis stratified by the randomized dose of pitavastatin, the risk for the primary endpoint was significantly lower in patients achieving both targets in both the 1mg and 4 mg arms, and in patients achieving only hs-CRP target in the 1 mg arm (Figure B, C).
Figure 1

Conclusions
In this subanalysis of the REAL-CAD trial, the hs-CRP lowering effect of pitavastatin was independent from LDL-C lowering. Lower achieved hs-CRP was associated with lower risk for cardiovascular events in Japanese patients with stable CAD.

Acknowledgement/Funding
Public Health Research Foundation, The company manufacturing the study drug (Kowa Pharmaceutical Co Ltd) was one of the entities providing financial s