PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients

Abstract

A real-world setting study of Familial hypercholesterolemia (FH) patients which received PCSK9 inhibitors in a specialized referral center in Mexico City. Ten patients between the age of 18-70 years and a diagnosis of FH according to DLCN criteria with failure to achieve LDL-C goals with standard therapy between 2016 and 2017 enrolled in a simple randomization in which a group of five participants received alirocumab (75 mg every two weeks) and the remaining five patients evolocumab (140 mg every two weeks). Comparative analysis was made analyzing the means of LDL at the baseline, at 4, 6, and 12 weeks. The evolocumab group had an average initial LDL-C of 277 mg/dL which, after 12 weeks of treatment, was significantly reduced to 116 mg/dL; p= 0.04 (IC95 11.5-310.9). The alirocumab group with a mean initial LDL-C of 229 mg/dL showed a reduction at 12 weeks of treatment to 80 mg/dL; p= 0.008 (IC95 63.8-233.7). In conclusion, PCSK9 inhibitors are an excellent treatment option in patients with FH who do not reach LDL-C goals with standard therapy or due to intolerance. There is no difference in the lipid-lowering effect between both PSCK9 inhibitors.

Effectiveness and safety of PCSK9 inhibitors in real-world clinical practice. An observational multicentre study. The IRIS-PCSK9I study

“…Likewise, some research has been undertaken with respect to routine clinical practice, including different population with hypercholesterolemia. Most reported real-life experiences are consistent with the clinical trials [ [21] , [22] , [23] , [24] , [25] , [26] , [27] ].…”

Proprotein convertase subtilisin/kexin type 9 inhibitors treatment in dyslipidemic patients: a real world prescription

“…One possible explanation could be the increased compliance with the PCSK9 inhibitors or with the suggested therapy as a whole. Our data are in line with what has been previously reported in the literature 26 …”

“…Our data are in line with what has been previously reported in the literature. 26 The FOURIER cardiovascular outcomes trial studied evolocumab vs placebo in 27564 patients with clinically evident ASCVD and on a moderate-to-high-intensity statin regimen over a median follow-up duration of 2.2 years. The trial showed a mean percentage reduction in LDL-C levels with evolocumab, as compared with placebo; the reduction was 59%, from a median baseline value of 92 mg/dl to 30 mg/dl.…”

Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials

“…PCSK9 inhibitors can be divided into those inhibiting the binding of PCSK9 to LDLR, and those inhibiting the expression or interfering with the secretion of PCSK9. PCSK9 monoclonal antibodies, alirocumab and evolocumab, were approved to treat FH in 2015 by the US Food and Drug Administration (FDA) [18]; however, the relationship between PCSK9 inhibitors and Lp(a) levels has not been fully studied [19]. Some studies indicated that evolocumab significantly reduces Lp(a) levels, more effectively than LDL-C plasmapheresis [20]; alirocumab reduced Lp(a) through an alternative pathway in addition to LDL-C reduction [21]; the ODYSSEY OUTCOMES demonstrated that Lp(a) predicted total cardiovascular event risk, and relative and absolute risk reduction in the placebo and alirocumab group [22]; while another showed no difference in circulating Lp(a) levels after 24 weeks of adalimumab or ezetimibe treatment [23].…”