AUTHOR=Chaiyasothi Thanaputt , Nathisuwan Surakit , Dilokthornsakul Piyameth , Vathesatogkit Prin , Thakkinstian Ammarin , Reid Christopher , Wongcharoen Wanwarang , Chaiyakunapruk Nathorn 

TITLE=Effects of Non-statin Lipid-Modifying Agents on Cardiovascular Morbidity and Mortality Among Statin-Treated Patients: A Systematic Review and Network Meta-Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00547

DOI=10.3389/fphar.2019.00547

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients.</p><p><bold>Methods:</bold> A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes.</p><p><bold>Results:</bold> Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72–0.93, <italic>p</italic> = 0.003), stroke (RR 0.74, 95% CI 0.65–0.85, <italic>p</italic> &lt; 0.001), coronary revascularization (RR 0.84, 95% CI 0.75–0.94, <italic>p</italic> = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST.</p><p><bold>Conclusions:</bold> None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients.</p>