VICTORION-INITIATE: LOW-DENSITY LIPOPROTEIN CHOLESTEROL GOAL ATTAINMENT AND CUMULATIVE EXPOSURE WITH “INCLISIRAN FIRST” VERSUS USUAL CARE IN PATIENTS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE

Abstract

Therapeutic Area

ASCVD /CVD Risk Reduction

Background

Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE, inclisiran allowed more patients with ASCVD to achieve and sustain LDL-C goals vs current usual care (UC).This study evaluated cumulative LDL-C exposure in the overall population and LDL-C goal attainment and safety in prespecified subgroups receiving an “inclisiran first” implementation strategy (IF; adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL with maximally tolerated statins) compared with UC.

Methods

VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial conducted at 45 sites across 20 states in the United States. Patients were randomized 1:1 (stratified by insurance status) to IF (open-label inclisiran 284 mg at Days 0, 90 and 270 plus UC) or UC alone, (lipid management directed by treating physician’s discretion). Subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (<1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]) and statin intolerance. Cumulative LDL-C exposure and safety by subgroup were also evaluated.

Results

Of 450 patients randomized to IF or UC, 11.1% and 84.2% had an ASCVD event <1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2% and 14.7% had a history of CHD, CVD or PAD, and 25.8% were statin intolerant. Cumulative exposure to LDL-C to Day 330 was >50% lower with IF vs UC (mean time-adjusted LDL-C: 42.4 mg/dL vs 90.7 mg/dL, (Figure). Significantly more patients on IF achieved LDL-C goals of <70 mg/dL and <55 mg/dL at Day 330 vs UC, irrespective of the subgroups (Table). Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between IF and UC (IF: 52.6%-71.2%, UC: 46.2%-66.0% and IF: 10.7%-28.3%, UC: 11.4%-22.2%, respectively).

Conclusions

Patients with ASCVD and LDL-C >70 mg/dL on IF had lower cumulative LDL-C exposure and achieved rapid and sustained LDL-C goals than those on UC, regardless of ASCVD subtype, event timing, and statin intolerance. The safety profile of IF was consistent across subgroups, with no differences in adverse events vs UC.