An "Inclisiran First" Strategy vs Usual Care in Patients With Atherosclerotic Cardiovascular Disease

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Atherosclerotic cardiovascular disease (ASCVD) patients often fail to meet low-density lipoprotein cholesterol (LDL-C) targets with standard therapies.
• Inclisiran, a twice-yearly therapy, demonstrates significant LDL-C reduction when added to statins.

Purpose of the Study:

• To evaluate the effectiveness of an "inclisiran first" strategy versus usual care in ASCVD patients with elevated LDL-C despite maximally tolerated statins.
• To compare LDL-C goal attainment and statin discontinuation rates between the two treatment strategies.

Main Methods:

• The VICTORION-INITIATE trial was a prospective, randomized, 1:1 trial comparing "inclisiran first" (inclisiran added immediately) plus usual care to usual care alone.
• Primary endpoints included percentage change in LDL-C from baseline and statin discontinuation rates.
• Patients received inclisiran 284 mg at days 0, 90, and 270, with lipid management at physician's discretion in the usual care arm.

Main Results:

• The "inclisiran first" strategy resulted in a significantly greater LDL-C reduction (60.0%) compared to usual care (7.0%) by day 330 (P < 0.001).
• More patients in the "inclisiran first" group achieved LDL-C goals (<70 mg/dL: 81.8% vs 22.2%; <55 mg/dL: 71.6% vs 8.9%; P < 0.001).
• Statin discontinuation rates were noninferior (6.0% vs 16.7%), and treatment-emergent adverse event rates were similar between groups, although injection-site events were more common with inclisiran.

Conclusions:

• An "inclisiran first" implementation strategy is effective in significantly lowering LDL-C in ASCVD patients.
• This strategy achieves superior LDL-C reduction without negatively impacting statin use or introducing new safety concerns.
• The findings support "inclisiran first" as a viable option for managing hyperlipidemia in high-risk cardiovascular patients.