{"title":"Choosing the optimal nonstatin lipid lowering therapies for statin-intolerant patients: A systematic review and network meta-analysis.","authors":"Wattakorn Laohapiboolrattana, Paisit Kosum, Mantiwee Nimworapan, Piyameth Dilokthornsakul, Kansak Boonpattharatthiti, Nonthikorn Theerasuwipakorn, Duangnapa Roongpiboonsopit, Pattamawan Kosuma, Teerapon Dhippayom","doi":"10.1016/j.jacl.2025.07.012","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Statin intolerance presents a considerable challenge in managing patients at risk for cardiovascular diseases, as it limits patients' access to standard lipid-lowering therapies.</p><p><strong>Objective: </strong>This study aims to compare the efficacy and safety of various nonstatin lipid-lowering therapies in patients who are intolerant to statins.</p><p><strong>Methods: </strong>We searched PubMed, Embase, CENTRAL, and EBSCO open dissertations through September 2023 for randomized controlled trials in statin-intolerant patients comparing nonstatin lipid-lowering agents. The primary outcome was low-density lipoprotein cholesterol (LDL-C). A random-effects model estimated comparative effects using mean differences (MDs) for LDL-C reduction and relative risks (RRs) for safety outcomes, specifically trial withdrawal due to adverse events. Results were reported with 95% CIs, and therapies ranked using the surface under the cumulative ranking curve (SUCRA). Evidence certainty was assessed with the Confidence in Network Meta-Analysis (CINeMA) platform.</p><p><strong>Results: </strong>Of 1533 articles, 6 studies (1326 patients) met inclusion criteria. Evolocumab combined with ezetimibe achieved the greatest LDL-C reduction (MD: 48.98%; 95% CI: 59.19, -38.77) vs ezetimibe alone, with moderate evidence certainty. Evolocumab, alirocumab, and the combination of bempedoic acid and ezetimibe, also showed significant reductions in LDL-C compared to ezetimibe monotherapy, though the magnitude of their effects was smaller than that of the evolocumab and ezetimibe combination. The SUCRA of evolocumab and ezetimibe (99.7%) aligns with its highest comparative efficacy. No significant differences in safety outcomes were observed across treatments.</p><p><strong>Conclusion: </strong>Evolocumab combined with ezetimibe is the most effective regimen for LDL-C reduction, with a safety profile comparable to other treatments, making it a viable alternative for patients with statin intolerance.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of clinical lipidology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jacl.2025.07.012","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Statin intolerance presents a considerable challenge in managing patients at risk for cardiovascular diseases, as it limits patients' access to standard lipid-lowering therapies.
Objective: This study aims to compare the efficacy and safety of various nonstatin lipid-lowering therapies in patients who are intolerant to statins.
Methods: We searched PubMed, Embase, CENTRAL, and EBSCO open dissertations through September 2023 for randomized controlled trials in statin-intolerant patients comparing nonstatin lipid-lowering agents. The primary outcome was low-density lipoprotein cholesterol (LDL-C). A random-effects model estimated comparative effects using mean differences (MDs) for LDL-C reduction and relative risks (RRs) for safety outcomes, specifically trial withdrawal due to adverse events. Results were reported with 95% CIs, and therapies ranked using the surface under the cumulative ranking curve (SUCRA). Evidence certainty was assessed with the Confidence in Network Meta-Analysis (CINeMA) platform.
Results: Of 1533 articles, 6 studies (1326 patients) met inclusion criteria. Evolocumab combined with ezetimibe achieved the greatest LDL-C reduction (MD: 48.98%; 95% CI: 59.19, -38.77) vs ezetimibe alone, with moderate evidence certainty. Evolocumab, alirocumab, and the combination of bempedoic acid and ezetimibe, also showed significant reductions in LDL-C compared to ezetimibe monotherapy, though the magnitude of their effects was smaller than that of the evolocumab and ezetimibe combination. The SUCRA of evolocumab and ezetimibe (99.7%) aligns with its highest comparative efficacy. No significant differences in safety outcomes were observed across treatments.
Conclusion: Evolocumab combined with ezetimibe is the most effective regimen for LDL-C reduction, with a safety profile comparable to other treatments, making it a viable alternative for patients with statin intolerance.
期刊介绍：
Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner.
Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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