“Inclisiran first” strategy highly effective regarding LDL control in ASCVD

Earlier introduction of inclisiran led to significantly reduced low-density lipoprotein (LDL) concentrations without affecting statin compliance in patients with atherosclerotic cardiovascular disease (ASCVD) in the phase 3b VICTORIAN-INITIATE trial. More than 80% of patients achieved the LDL treatment goal of ≤70 mg/dL.

Inclisiran is a first-in-class, long-acting, synthetic small-interfering RNA molecule directed against PCSK9, which has been shown to cause a marked reduction in LDL-C levels. Twice-yearly injections can lower LDL concentration by an additional 50%. In the current prospective, multicenter, randomised, open-label phase 3b trial VICTORION-INITIATE (NCT04929249), Dr Michael Koren (Jacksonville Center for Clinical Research, FL, USA) and his coworkers assessed whether an “inclisiran first” implementation strategy (i.e. adding inclisiran immediately when patients fail to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) can help to control LDL concentrations in patients with a history of ASCVD.

All 450 participants received maximum tolerated statin therapy or had documented statin intolerance without achieving LDL-C ≤70 mg/dL. They were randomly assigned to the “inclisiran first” strategy or usual care with lipid-lowering therapy left to the treating physician's discretion. The study's co-primary endpoints were the percentage change in LDL-C from baseline to day 330 and the discontinuation of statin therapy, defined as no statin use for ≥30 days before the end-of-study visit.

At day 330, the mean percentage change in LDL-C from baseline was -60.0% (97.5% CI -64.7 to -55.2) with the “inclisiran first” intervention and only -7.0% (97.5% CI -12.0 to -1.9) with usual care; a statistically significant difference (LS mean difference -53.0%; 97.5% CI -60.0 to -46.0; P<0.001). Statin discontinuation rates with “inclisiran first” (6.0%) were non-inferior versus usual care (16.7%). In the “inclisiran first” group, 81.8% of participants met their LDL treatment goal compared with 22.2% in the usual care group (P<0.0001).

The safety profile of both approaches was similar, except for injection-site reactions that were more frequent in the “inclisiran first” strategy (10.3% versus 0 in the usual care group).

1. Koren MJ, et al. Comparison of an "Inclisiran First" strategy with usual care in patients with atherosclerotic cardiovascular disease: results from the VICTORION-INITIATE randomized trial. LB2, Session 405,ACC 2024 Scientific Session, 6–8 April, Atlanta, USA.

Medical writing support was provided by Dr Susanne Kammerer.
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Posted on 9 April, 2024