The comparative impact among different intensive statins and combination therapies with niacin/ezetimibe on carotid intima-media thickness: a systematic review, traditional meta-analysis, and network meta-analysis of randomized controlled trials



To compare the impact of different statins therapies on the reduction of carotid intima-media thickness (CIMT) may reflect their cardiovascular benefits which is useful in clinical decision.


PubMed, EMBASE, Cochrane Library, and Web of Science were searched, and 3539 articles published from 1992 to 2020 were retrieved. CIMT in randomized controlled trials for statins therapies were included for traditional and network meta-analyses analyzed by Stata 16. The quality of included studies was assessed by the Cochrane Collaboration’s tool.


Thirty-three randomized controlled trials (n=8762) were eligible for network meta-analysis, of which 18 randomized controlled trials (n=5252) were included for comparison between statins and no statins and 11 randomized controlled trials (n=1338) were included for comparison between high-intensity statins or combination with niacin/ezetimibe and moderate/low-intensity statins in 2 traditional meta-analyses. In the traditional meta-analyses, the statins groups significantly reduce CIMT compared to no statins (standard mean difference=−0.207, 95% confidence interval: −0.291 to −0.123, p<0.001), while high-intensity statins or combination with niacin/ezetimibe performed significant CIMT reduction compared to moderate/low-intensity statins (standard mean difference=−0.287, 95% confidence interval: −0.460 to −0.114, p=0.001). In the network meta-analysis, a relative rank for the ability to reduce CIMT was given as follows: combination therapy with niacin (mean rank: 1.7), high-intensity statins, combination therapy with ezetimibe, and moderate/low-intensity statins.


Statins combined with niacin performed a greater CIMT reduction compared to high-intensity statins alone and combination therapies with ezetimibe. The advantage of niacin-combined statins therapies to improve cardiovascular endpoint needs further validation through randomized controlled trials.

Clinical trial registration

PROSPERO, CRD42020175972

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Data Availability

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This work was supported by the National Natural Science Foundation of China (NSFC) [No. 81970388, No. 81700397, No. 81903299, No.81801719], the Natural Science Foundation of Guangdong [No. 2019A1515011682], the Key S&T Special Project of Guangzhou [No. 201704020044], and the Yat-sen Launching Project [No. YXQH202014].

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HWL: data curation, formal analysis, investigation, and roles/writing—original draft. XLX: data curation, funding acquisition, investigation, and methodology. LML: methodology and supervision. RLS: validation and visualization. QG: funding acquisition and validation. QC: data curation and funding acquisition. JJW: visualization. ZJH: visualization. YLZ: conceptualization, funding acquisition, supervision, and writing—review and editing.

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Correspondence to Yuling Zhang.

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Li, H., Xu, X., Lu, L. et al. The comparative impact among different intensive statins and combination therapies with niacin/ezetimibe on carotid intima-media thickness: a systematic review, traditional meta-analysis, and network meta-analysis of randomized controlled trials. Eur J Clin Pharmacol (2021).

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  • Statins
  • Niacin
  • Ezetimibe
  • Carotid intima-media thickness
  • Network meta-analysis