P832LDL-C levels on statins and cardiovascular event risk in stable coronary artery disease: An observation from the REAL-CAD study

Abstract

Background The relation between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and the cardiovascular event risk is still unclear in patients receiving the same doses of statins. Methods From the REAL-CAD study comparing high-dose with low-dose pitavastatin therapy in Japanese patients with stable coronary artery disease, 11105 patients without reported non-adherence for the study drug were divided into 3 groups according to the on-treatment LDL-C level at 6-month (<70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL; N=1016, N=3078, and N=1665 in the pitavastatin 1 mg/day stratum; N=2431, N=2524, and N=391 in the pitavastatin 4 mg/day stratum). Primary outcome measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission. Results In the pitavastatin 1 mg/day stratum, cumulative 4-year incidence of the primary outcome measure was not significantly different across the 3 groups (5.0%, 5.7%, and 5.2%, P=0.51), while in the 4 mg/day stratum, it was significantly higher in the LDL-C ≥100 mg/dL group than in other groups (4.5%, 3.4%, and 9.1%, P<0.001). The adjusted risks of the LDL-C <70 mg/dL group relative to the LDL-C 70–100 mg/dL group (reference) remained insignificant for the primary outcome measure in both 1 mg/day and 4 mg/day strata (HR 0.84, 95% CI 0.58–1.18, P=0.32, and HR 1.25, 95% CI 0.88–1.79, P=0.22). The adjusted risk of LDL-C ≥100 mg/dL group relative to the reference group was not significant for the primary outcome measure in the 1 mg/day stratum (HR 0.82, 95% CI 0.60–1.11, P=0.21), while it was highly significant in the 4 mg/day stratum (HR 3.32, 95% CI 2.08–5.17, P<0.001). In the on-treatment LDL-C ≥100 mg/dL group in the 4 mg/day stratum, LDL-C increased by 6.3 mg/dL from baseline to 6-month despite dose escalation of pitavastatin from 1 mg/day to 4 mg/day, suggesting the presence of unreported poor adherence in this small subgroup. Adjusted Effects of On-treatment LDL-C Conclusions Very low on-treatment LDL-C level (<70 mg/dL) was not associated with lower cardiovascular event risk compared with moderately low on-treatment LDL-C level (70–100 mg/dL) in patients receiving the same doses of statins. Too much emphasis on the target LDL-C strategy might mislead the clinical practice. Acknowledgement/Funding The Comprehensive Support Project for Clinical Research of Lifestyle-Related Disease of the Public Health Research Foundation.