Background: The prevalence of Familial Hypercholesterolemia (FH) is estimated to be 1 in 250 US adults. The advent of PCSK9 inhibitors has led a to a paradigm shift in the management of these patients. The purpose of this study was to analyze the efficacy of PCSK9 inhibitors in patients with heterozygous or homozygous FH.
Methods: Pubmed, EMBASE and clinicaltrials.gov were searched for randomized controlled trials of PCSK9 inhibitors. Trials that exclusively recruited FH patients or those that reported data separately for FH patients were included. The primary outcome of this analysis was mean difference in LDL-C in patients treated with a PCSK9 inhibitor compared with placebo. Secondary endpoints were change in other lipids and incidence of adverse events. A random effects model was used to analyze the pooled estimates.
Results: A pooled analysis of 9 trials with a total of 1361 patients was performed. Overall the mean difference in LDL-C reduction with PCSK9 inhibition was -48.6% (95% CI: -51.3 to -45.9; p<0.001), as compared with placebo. There was no significant difference in LDL-C reduction between trials using alirocumab vs. those using evolocumab. There was significant heterogeneity among the included trials I2=75.9%. The risk of bias in all included studies was low.
Conclusions: Among patients with FH, PCSK9 inhibitors were highly effective and reduced LDL-C levels by nearly 50% compared with placebo. No differences in magnitude of reduction were observed between alirocumab and evolocumab.