2SPD-018 Adjusted indirect comparison between plozasiran and zodasiran in mixed hyperlipidemia

<h3>Background and Importance</h3> Plozasiran and zodasiran are RNA interference agents developed for the treatment of mixed hyperlipidemia. No direct comparisons between these drugs have been performed. <h3>Aim and Objectives</h3> To conduct adjusted indirect comparisons (AICs) on efficacy between plozasiran and zodasiran in mixed hyperlipidemia. <h3>Material and Methods</h3> A search was developed in Pubmed database to select pivotal randomised clinical trials (RCTs) including plozasiran and zodasiran in mixed hyperlipidemia. These RCTs had to presented comparable populations, follow-up periods, endpoints and comparator arms. AICs of regimens with best benefit-risk balance were developed using Bucher’s method on the following endpoints: percentage change in plasma levels from baseline to week 24 of fasting triglyceride, non-HDL cholesterol, ApoB, LDL cholesterol, HDL cholesterol, remnant cholesterol and lipoprotein (a). The absolute risk reduction (ARR) was calculated for AICs. <h3>Results</h3> Two phase II RCTs were selected, one of each drug. A total of 557 patients were included. Doses of plozasiran 25 mg quarterly (PLOZ-25q) and zodasiran 200 mg (ZOD-200) were selected based on their superior risk-benefit balance. Placebo was common comparator. AIC limitations: short patient follow-up and minor differences in population characteristics (percentage of high-intensity statins and fibrates received). The results of the trials and AICs are shown in table 1. <h3>Conclusion and Relevance</h3> Significant favourable differences on differing surrogate endpoints were found for PLOZ-25q (HDL cholesterol) and ZOD-200 (non-HDL cholesterol, LDL cholesterol, remnant cholesterol) in mixed hyperlipidaemia. RCTs with harder endpoints and longer follow-up are needed to establish better therapeutic positioning. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest