The efficacy advantage of evolocumab (AMG 145) dosed at 140mg every 2weeks versus 420mg every 4weeks in patients with hypercholesterolemia: Evidence from a meta-analysis.
BACKGROUND
Evolocumab (AMG 145), a PCSK9 inhibitor, has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels. Doses of 140mg administered every 2weeks (Q2W) and 420mg administered every 4weeks (Q4W) are widely used, and both dosing schedules were effective in clinical trials. However, some researchers have speculated that 140mg Q2W administration has equal or even greater efficacy. This meta-analysis was performed to assess the differences in efficacy and safety between the two doses.


METHODS
We searched the PubMed, EMBASE, and Web of Science databases to identify relevant clinical trials published before January 2016. A total of 2403 patients from 8 randomized controlled trials were identified and included in the analysis.


RESULTS
Evolocumab administered at 140mg Q2W resulted in a greater percent change from baseline in LDL-C concentration (-7.27; 95% confidence interval (CI), -10.36 to -4.18) and had greater efficacy in achieving the treatment goal of LDL-C ≤1.8mmol/L with an relative risk (RR) of 1.09 (95% CI, 1.00 to 1.18) compared with 420mg Q4W in patients who were concomitantly treated with statins. These findings were not significantly different between the 140mg Q2W and 420mg Q4W groups when evolocumab was administered as monotherapy. There was no difference in the rate of occurrence of the main treatment-related adverse events between the two doses.


CONCLUSIONS
Evolocumab administered at 140mg Q2W was more effective than the 420mg Q4W dosage at lowering lipid concentrations, especially in patients who concomitantly received stable statin therapy.
Key Laboratory of Geriatrics of Health Ministry, Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiao-Xiao
XX
He
Key Laboratory of Geriatrics of Health Ministry, Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Rong
R
Zhang
Key Laboratory of Geriatrics of Health Ministry, Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Pei-Yuan
PY
Zuo
Key Laboratory of Geriatrics of Health Ministry, Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yu-Wei
YW
Liu
Key Laboratory of Geriatrics of Health Ministry, Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiang-Nan
XN
Zha
Key Laboratory of Geriatrics of Health Ministry, Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sheng-Shuai
SS
Shan
Key Laboratory of Geriatrics of Health Ministry, Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: lcyun2016@163.com.
Cheng-Yun
CY
Liu
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000091362:PCSK9 Inhibitors; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C577155:evolocumab
Evolocumab; Low density lipoprotein cholesterol; Meta-analysis; Proprotein convertase subtilisin/kexin type 9; Randomized controlled trials