Long Term LDL-C Trajectories under Sequential PCSK9 Inhibition: Descriptive Findings from the ORION-3 Switching Arm

The ORION-3 study offered a unique opportunity to characterize long term LDL-C trajectories within the same individuals undergoing sequential PCSK9 inhibition—initially with evolocumab and subsequently with inclisiran. This secondary descriptive analysis was based exclusively on published aggregate data from ORION-3. LDL-C values were extracted from reported summary statistics. In the switching arm, participants received evolocumab 140 mg every two weeks for one year before transitioning to inclisiran 300 mg every six months from day 361 onward. LDL-C was calculated using the Friedewald formula, and missing values were not imputed. Absolute LDL-C values were summarized descriptively at predefined time points. Evolocumab induced a rapid LDL-C reduction, reaching 45.3 mg/dL at day 90 (n = 88). Day 360 represented the final on treatment assessment during evolocumab therapy (mean LDL-C 64.0 mg/dL; n = 86). After switching to inclisiran, LDL-C remained substantially reduced through long term follow up, with a mean of 70.4 mg/dL at day 1440 (n = 79). Sequential PCSK9 inhibition with evolocumab followed by inclisiran maintained robust LDL-C lowering over four years. These descriptive within patient observations reflect expected pharmacodynamic differences between monoclonal antibody and siRNA based PCSK9 inhibition without implying comparative treatment efficacy.