In-hospital inclisiran for early LDL-C lowering after atherosclerotic ischemic stroke: an observational pilot study

Guidelines recommend low-density lipoprotein cholesterol (LDL-C) below 55 mg/dL and a ≥ 50% reduction in very-high-risk patients, including after atherosclerotic stroke. Recurrence risk peaks in the acute phase, yet oral therapy reaches target slowly. Early in-hospital use of inclisiran after stroke is largely unexplored. To assess the feasibility of in-hospital inclisiran after high-risk ischemic stroke and describe the early LDL-C trajectory. Single-arm observational pilot study from a prospective single-center registry. Fifteen consecutive adults with ischemic stroke due to large-artery atherosclerosis or branch atheromatous disease meeting Italian fast-track reimbursement criteria received inclisiran 284 mg during admission on top of intensified oral therapy. LDL-C was measured at baseline, days 3, 7, 10, 14, and three months. Fifteen of 18 eligible patients (83.3%) were treated, a median of 3 days after the LDL-C result. Baseline LDL-C was 138 mg/dL and fell to 75 and 31 mg/dL at days 3 and 14 after the dose (median reductions 45% and 77%). The composite goal (≥ 50% reduction from the acute-phase baseline and LDL-C < 55 mg/dL) was met by 33.3% at day 7, 80.0% at day 14, and 86.7% at a median of 87 days. Oral therapy was modified in 13 patients, so inclisiran's contribution cannot be isolated. No recurrent stroke or inclisiran-related adverse event occurred. In-hospital inclisiran was feasible, and most patients reached the goal within two weeks of the combined regimen. These hypothesis-generating findings warrant a controlled study measuring proprotein convertase subtilisin/kexin type 9, with clinical outcomes and longer follow-up.