Yasuyoshi Ouchi1, Jun Sasaki2, Hidenori Arai3, Koutaro Yokote4, Kazumasa Harada5, Yasuo Katayama6, Takao Urabe7, Yasufumi Uchida8, Masaru Hayashi9, Naoto Yokota10, Hirokazu Nishida11, Takatoshi Otonari12, Tadashi Arai13, Ichiro Sakuma14, Kazuo Sakabe15, Masayasu Yamamoto16, Takashi Kobayashi17, Shinichi Oikawa18, Shizuya Yamashita19, Hiromi Rakugi20, Takumi Imai21, Shiro Tanaka21, Yasuo Ohashi22, Masanari Kuwabara1, Hideki Ito5. 1. Toranomon Hospital, Tokyo, Japan (Y. Ouchi, M.K.). 2. International University of Health and Welfare, Fukuoka, Japan (J.S.). 3. National Center for Geriatrics and Gerontology, Obu, Japan (H.A.). 4. Chiba University, Chiba, Japan (K.Y.). 5. Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan (K.H., H.I.). 6. General Tokyo Hospital, Tokyo, Japan (Y.K.). 7. Juntendo University Urayasu Hospital, Urayasu, Japan (T.U.). 8. Saga Memorial Hospital, Saga, Japan (Y.U.). 9. Nagahama City Hospital, Nagahama, Japan (M.H.). 10. Yokota Clinic, Miyazaki, Japan (N.Y.). 11. Nishida Clinic, Neyagawa, Japan (H.N.). 12. Otonari Clinic, Chikushino, Japan (T.O.). 13. Arai Clinic, Yamagata, Japan (T.A.). 14. Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan (I.S.). 15. Sakabe Clinic, Kyoto, Japan (K.S.). 16. Yamamoto Clinic, Shimoniikawa, Japan (M.Y.). 17. Jyuzen General Hospital, Niihama, Japan (T.K.). 18. Fukujuji Hospital, Tokyo, Japan (S.O.). 19. Rinku General Medical Center, Izumisano, Japan (S.Y.). 20. Osaka University, Suita, Japan (H.R.). 21. Kyoto University, Japan (T.I., S.T.). 22. Chuo University, Tokyo, Japan (Y. Osachi).
Abstract
BACKGROUND: Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged ≥75 years, is insufficient. This trial tested whether LDL-C-lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients. METHODS: This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged ≥75 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke. RESULTS: Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibe patients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50-0.86; P=0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37-0.98; P=0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18-0.79; P=0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups. CONCLUSIONS:LDL-C-lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged ≥75 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution. Clinical Registration: URL: https://www.umin.ac.jp. Unique identifier: UMIN000001988.
RCT Entities:
BACKGROUND: Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged ≥75 years, is insufficient. This trial tested whether LDL-C-lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients. METHODS: This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged ≥75 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke. RESULTS: Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibepatients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50-0.86; P=0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37-0.98; P=0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18-0.79; P=0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups. CONCLUSIONS:LDL-C-lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged ≥75 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution. Clinical Registration: URL: https://www.umin.ac.jp. Unique identifier: UMIN000001988.
Authors: Baris Gencer; Nicholas A Marston; KyungAh Im; Christopher P Cannon; Peter Sever; Anthony Keech; Eugene Braunwald; Robert P Giugliano; Marc S Sabatine Journal: Lancet Date: 2020-11-10 Impact factor: 202.731
Authors: Christopher P Cannon; James A de Lemos; Robert S Rosenson; Christie M Ballantyne; Yuyin Liu; Qi Gao; Tamara Palagashvilli; Shushama Alam; Katherine E Mues; Deepak L Bhatt; Mikhail N Kosiborod Journal: JAMA Cardiol Date: 2021-06-16 Impact factor: 14.676