PCSK9 inhibitors show superior LDL-C lowering effects to ezetimibe
Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor is superior to ezetimibe in reducing low-density lipoprotein cholesterol (LDL-C), with or without statin therapy, according to a study presented at the Asian Pacific Society of Cardiology Congress 2018 (APSC 2018) in Taipei, Taiwan. Additionally, PCSK9 inhibitor shows comparable safety profile.
The investigators searched for medical journals using PubMed, Cochrane, Springer, Trip Database and Science Direct. Included were randomized clinical trials (RCTs) or meta-analyses of RCTs, studies in patients with hypercholesterolaemia, and comparison research using PCSK9 inhibitor drugs and ezetimibe.
Non-English studies, animal studies, opinion articles and articles with no abstract were not included in the analysis. A total of three articles were selected and analysed after applying the inclusion and exclusion criteria. [APSC 2018, abstract P001]
In LAPLACE II trial, the PCSK9 inhibitor evolocumab showed superior LDL-C–lowering effect vs ezetimibe (high-intensity statin group: mean LDL-C change from baseline of week 10–12, 65.1 percent; 95 percent CI, –69.8 percent to –60.3 percent vs –21.3 percent; –28.0 percent to –14.5 percent; p<0.001; moderate intensity statin group: mean LDL-C change, –62.5 percent; –66.1 percent to –58.2 percent vs –19.0 percent; –24.0 percent to –13.9 percent; p<0.001).
The ODYSSEY Combo II trial, which compared alirocumab with ezetimibe in high cardiovascular risk patients, showed comparable results, with mean LDL-C change from baseline of –52.4 percent for alirocumab and –21.8 percent for ezetimibe (p<0001). Safety profile appeared to be similar between the PCSK9 inhibitor and ezetimibe.
The GAUSS-3 trial, which compared evolocumab with ezetimibe in patients with muscle-related statin intolerance, showed that while mean LDL-C change from baseline was –52.8 percent (–55.8 percent to –49.8 percent) for evolocumab and –16.7 percent (–20.8 percent to –12.5 percent) for ezetimibe (p<0.001), any muscle-related adverse events occurrence percentage only led to a nonsignificant 20.7 percent for evolocumab and 28.8 percent for ezetimibe (hazard ratio, 0.68; 0.39–1.19; p=0.17).
Further research is warranted to determine the long-term effects of PCSK9 inhibitors on cardiovascular risk and safety, according to the investigators.
In a recent study, Pandey and colleagues suggested that widespread clinical adoption of PCSK9 inhibitors will depend on the results from ongoing and planned cardiovascular efficacy and safety trials with the study drug. Also, understanding the practical challenges and barriers to the use of these medications by high cardiovascular risk patients will affect the clinical adoption of these agents. [Curr Opin Cardiol 2017;32:633-641]
Statin administration has been the standard for managing patients with hypercholesterolaemia, but a significant proportion of patients do not respond positively to statin monotherapy. Some cannot tolerate statins, while others do not reach adequate levels of LDL-C reduction despite optimal statin dose.
“Nonstatin alternatives, such as ezetimibe and PCSK9 inhibitor (eg, alirocumab and evolocumab), open new possibilities for more optimal LDL-C control on these patients,” the investigators said.