Chi-kin Ip1, Dong-mei Jin2, Jia-jia Gao3, Zhe Meng4, Jing Meng5, Zhi Tan6, Jing-feng Wang7, Deng-feng Geng8. 1. Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China. 2. Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. 3. Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China; Shenzhen Sun Yixian Cardiovascular Hospital, Shenzhen 518001,China. 4. Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. 5. Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China. 6. Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510120, China. 7. Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China. Electronic address: dr.wangjf@hotmail.com. 8. Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China. Electronic address: dr.dfengg@hotmail.com.
Abstract
BACKGROUND: In patients at high risk of atherosclerotic cardiovascular diseases (ASCVDs), residual cardiovascular risk persists despite the achievement of target LDL cholesterol levels with statin therapy. It is still unclear whether adding lipid-modifying agent to statin treatment can further improve clinical outcomes. METHODS: Randomized controlled trials (RCTs) in terms of adding lipid-modifying agent to statin versus statin monotherapy in patients at high risk of ASCVD were identified by electronic and manual searches. Results were expressed as relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Eleven RCTs with 109,244 patients were included in this meta-analysis. Overall, the incidences of major adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups and 9.92% in the statin monotherapy groups. No significant difference was observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05, P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37; niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88-1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97, P=0.004). Adding lipid-modifying agent to statin significantly increased liver injury risk. Adding ezetimibe to statin did not alter side effect profile. CONCLUSION: Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin therapy further lowers LDL-cholesterol safely and translates into a clinical benefit in patients at high risk of ASCVD.
BACKGROUND: In patients at high risk of atherosclerotic cardiovascular diseases (ASCVDs), residual cardiovascular risk persists despite the achievement of target LDL cholesterol levels with statin therapy. It is still unclear whether adding lipid-modifying agent to statin treatment can further improve clinical outcomes. METHODS: Randomized controlled trials (RCTs) in terms of adding lipid-modifying agent to statin versus statin monotherapy in patients at high risk of ASCVD were identified by electronic and manual searches. Results were expressed as relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Eleven RCTs with 109,244 patients were included in this meta-analysis. Overall, the incidences of major adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups and 9.92% in the statin monotherapy groups. No significant difference was observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05, P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37; niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88-1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97, P=0.004). Adding lipid-modifying agent to statin significantly increased liver injury risk. Adding ezetimibe to statin did not alter side effect profile. CONCLUSION: Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin therapy further lowers LDL-cholesterol safely and translates into a clinical benefit in patients at high risk of ASCVD.
Authors: Stefan Schandelmaier; Matthias Briel; Ramon Saccilotto; Kelechi K Olu; Armon Arpagaus; Lars G Hemkens; Alain J Nordmann Journal: Cochrane Database Syst Rev Date: 2017-06-14