ASCVD is the primary cause of death for women despite having a later onset than it is for men, and mortality is greater for women than it is for men. The disparity may be caused by differences in the diagnosis and management of CVD risk factors. A new siRNA called Inclisiran reduced LDL-C and prevented the creation of PCSK9. Patients with HeFH (ORION-9), ASCVD (ORION-10, -11), and ASCVD risk equivalents participated in three Phase III placebo-controlled studies to assess the effectiveness and safety of inclisiran (ORION-11). For a study, researchers sought to evaluate how sex affected inclisiran’s safety and effectiveness profile.
Sex was used to group patients from each experiment. The co-primary outcomes were time-adjusted percentage change in LDL-C from baseline after Day 90 up to Day 540 and percentage change in LDL-C from baseline to Day 510. The 18-month evaluation period was used to evaluate secondary effectiveness and safety criteria.
There were 3,660 patients in total, of which 1,190 (32.5%) were female and 2,470 (67.5%) were male. In comparison to men, women were more likely to have ASCVD-risk equivalent (26.4% vs. 9.7%), were less likely to take statins (high-intensity statins) (90% [70% vs. 93% [76%]), and were less likely to obtain statins. Both co-primary objectives showed comparable effectiveness of inclisiran vs. placebo in both sexes. Females had higher LDL-C at baseline (122.9 mg/dL vs 105.8 mg/dL), and (secondary endpoints) placebo-corrected mean absolute decrease in LDL-C at Day 510 (62.6 vs 54.0 mg/dL, P<0.05) and time-adjusted reduction from Days 90 to 540 (59.0 vs 51.5 mg/dL, P<0.05) with inclisiran were larger in females. With the exception of injection-site AEs, which were more common in the inclisiran arm than the placebo (females 9.4% vs 0.2%, men 2.8% vs 0.9%), the majority of AEs were similar between inclisiran vs placebo for both sexes.
With the exception of greater injection-site adverse events (AEs) from inclisiran (mostly mild) compared to placebo, which was more common in females, the effectiveness and safety profile of inclisiran were usually similar in both sexes.
Reference: ahajournals.org/doi/10.1161/circ.142.suppl_3.16311
