Junichi Yamaguchi1, Erisa Kawada-Watanabe2, Ryo Koyanagi2, Hiroyuki Arashi2, Haruki Sekiguchi2, Koichi Nakao3, Tetsuya Tobaru4, Hiroyuki Tanaka5, Toshiaki Oka6, Yasuhiro Endo7, Katsumi Saito8, Tatsuro Uchida9, Kunihiko Matsui10, Hiroshi Ogawa2, Nobuhisa Hagiwara2. 1. Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, 162-8666, Japan. Electronic address: j.yamaguchi0110@gmail.com. 2. Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, 162-8666, Japan. 3. Saisei-Kai Kumamoto Hospital, Kumamoto, 861-4193, Japan. 4. Sakakibara Heart Institute, Tokyo, 183-0003, Japan. 5. Tokyo Metropolitan Tama Medical Center, Tokyo, 183-5111, Japan. 6. Seirei Hamamatsu General Hospital, Shizuoka, 430-8558, Japan. 7. Saisei-Kai Kurihashi Hospital, Saitama, 349-1105, Japan. 8. Nishiarai Heart Center, Tokyo, 123-0845, Japan. 9. Cardiovascular Center of Sendai, Miyagi, 981-3133, Japan. 10. Department of General and Community Medicine, Kumamoto University Hospital, Kumamoto, 860-8556, Japan.
Abstract
BACKGROUND AND AIMS: We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia. METHODS: This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined. RESULTS: The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy. CONCLUSIONS: Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach.
BACKGROUND AND AIMS: We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndromepatients with dyslipidaemia. METHODS: This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined. RESULTS: The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy. CONCLUSIONS: Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach.
Authors: Oliver Weingärtner; Dieter Lütjohann; Sven Meyer; Arne Fuhrmann; Bodo Cremers; Sarah Seiler-Mußler; Hans-F Schött; Anja Kerksiek; Silvia Friedrichs; Ursula Ulbricht; Adam Zawada; Ulrich Laufs; P Christian Schulze; Bruno Scheller; Danilo Fliser; Michael Böhm; Eric Sijbrands; Gunnar H Heine Journal: Clin Res Cardiol Date: 2019-04-04 Impact factor: 5.460
Authors: Insa E Emrich; Gunnar H Heine; P Christian Schulze; Kyrill S Rogacev; Danilo Fliser; Stefan Wagenpfeil; Michael Böhm; Dieter Lütjohann; Oliver Weingärtner Journal: Pharmacol Res Perspect Date: 2021-08