Effectiveness and safety of atorvastatin/ ezetimibe fixed-dose combination in hypercholesterolemia: a systematic review and network meta-analysis
- 1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
- 2Medical Affairs and Outcomes Research, Organon China, Shanghai, China
Abstract
Background: Many patients fail to achieve low-density lipoprotein cholesterol (LDL-C) targets with statin monotherapy, calling for a combination of statins and ezetimibe. This systematic review and network meta-analysis evaluated the comparative effectiveness and safety of atorvastatin monotherapy, atorvastatin/ezetimibe free-equivalent combination (AS/EZ FEC), and fixed-dose combination (AS/EZ FDC) in patients with hypercholesterolemia.
Methods: Randomized controlled trials were retrieved from electronic databases. Primary outcomes were the percentage change in LDL-C from baseline and LDL-C goal attainment, analyzed using mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI). Treatments were ranked via surface under the cumulative ranking curve (SUCRA). The two combination therapies were compared to AS alone for their safety profiles and tolerability. Forty-six trials ( n = 10,567) were included.
Results: AS/EZ FDC reduced LDL-C more than AS alone (MD −13.94%, 95% CI [−18.90% to −9.10%]), with similar results for AS/EZ FEC (MD −12.41%, 95% CI [−14.61% to −10.22%]). SUCRA rankings for LDL-C reduction were FDC (86.2%), FEC (63.8%), and AS (0.0%). For LDL-C goal attainment, the RR was 1.87 (95% CI [1.47–2.39]) for FEC vs. monotherapy, 1.80 (95% CI [0.85–3.81]) for FDC vs. monotherapy. No significant differences in safety profiles were observed between treatments.
Conclusion: AS/EZ combination therapies provide greater improvements in LDL-C reduction and goal attainment compared with AS monotherapy, with FDC ranking highest in LDL-C reduction. Treatment with AS/EZ FEC or FDC did not increase the risk of adverse events compared to AS monotherapy and was well tolerated. These findings support FDC use when intensive LDL-C lowering is required.
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BibTeX
@article{qian2026effectiveness,
title = {{Effectiveness and safety of atorvastatin/ ezetimibe fixed-dose combination in hypercholesterolemia: a systematic review and network meta-analysis}},
author = {Juying Qian and Xingxin Zhang and Qing Li and Sisi Chen},
journal = {PeerJ},
year = {2026},
month = oct,
doi = {10.7717/peerj.21784},
url = {https://peerj.com/articles/21784},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Effectiveness and safety of atorvastatin/ ezetimibe fixed-dose combination in hypercholesterolemia: a systematic review and network meta-analysis
AU - Juying Qian
AU - Xingxin Zhang
AU - Qing Li
AU - Sisi Chen
PY - 2026
DA - 2026/10/21
JO - PeerJ
DO - 10.7717/peerj.21784
UR - https://peerj.com/articles/21784
AB - Background: Many patients fail to achieve low-density lipoprotein cholesterol (LDL-C) targets with statin monotherapy, calling for a combination of statins and ezetimibe. This systematic review and network meta-analysis evaluated the comparative effectiveness and safety of atorvastatin monotherapy, atorvastatin/ezetimibe free-equivalent combination (AS/EZ FEC), and fixed-dose combination (AS/EZ FDC) in patients with hypercholesterolemia. Methods: Randomized controlled trials were retrieved from electronic databases. Primary outcomes were the percentage change in LDL-C from baseline and LDL-C goal attainment, analyzed using mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI). Treatments were ranked via surface under the cumulative ranking curve (SUCRA). The two combination therapies were compared to AS alone for their safety profiles and tolerability. Forty-six trials ( n = 10,567) were included. Results: AS/EZ FDC reduced LDL-C more than AS alone (MD −13.94%, 95% CI [−18.90% to −9.10%]), with similar results for AS/EZ FEC (MD −12.41%, 95% CI [−14.61% to −10.22%]). SUCRA rankings for LDL-C reduction were FDC (86.2%), FEC (63.8%), and AS (0.0%). For LDL-C goal attainment, the RR was 1.87 (95% CI [1.47–2.39]) for FEC vs. monotherapy, 1.80 (95% CI [0.85–3.81]) for FDC vs. monotherapy. No significant differences in safety profiles were observed between treatments. Conclusion: AS/EZ combination therapies provide greater improvements in LDL-C reduction and goal attainment compared with AS monotherapy, with FDC ranking highest in LDL-C reduction. Treatment with AS/EZ FEC or FDC did not increase the risk of adverse events compared to AS monotherapy and was well tolerated. These findings support FDC use when intensive LDL-C lowering is required.
SN - 2167-8359
ER -