In ORION-10 (N=1561) on top of a maximally tolerated statin, LEQVIO demonstrated:

52% LDL-C reduction in patients with ASCVD vs placebo at month 17 (95% CI: -56%, -49%; P<0.0001)¹

84% of patients achieved LDL-C target^* compared with 18% of patients on placebo at month 17³

Results were similar in patients with ASCVD or those at increased risk of CVD^† in ORION-11.¹

Study Design: ORION-10 (N=1561) & ORION-11 (N=1617) were multicenter, double-blind, randomized, placebo-controlled, 18-month, phase 3 trials in patients with established ASCVD (ORION-10 and ORION-11) or increased risk for CVD^† (ORION-11). Patients were taking a maximally tolerated statin with or without other lipid-modifying therapy and required additional LDL-C reduction. The primary efficacy measure was the percentage change in LDL-C from baseline to day 510.^1,4

^*LDL-C target was <70 mg/dL for patients with ASCVD.^1
†Factors that increase risk of CVD include HeFH, T2DM, or 10-year risk of ≥20%.⁴

V-INITIATE: LEQVIO vs usual care arm in a real-world setting

V-INITIATE compared immediate LEQVIO use after failure to reach LDL-C target^‡ with maximally tolerated statin vs usual care, which was physician-determined based on the 2018 AHA/ACC guidelines.²

In the usual care arm, most patients (73%) remained on statins only, with a minority of patients receiving any additional nonstatin lipid-lowering therapy, including 10 patients who received at least 1 dose of LEQVIO.²

^‡Guideline-recommended LDL-C target was <70 mg/dL for patients with ASCVD.^4,5

Early LEQVIO use after failure to reach LDL-C target on statin²

LDL-C reduction with LEQVIO vs usual care 

6% of patients in the LEQVIO arm vs 17% of patients in the usual care arm discontinued statins^§
[-11% (97.5% CI: -18%, -3%)]^2
§Statin discontinuation defined as no statin use for ≥30 days in patients without a history of statin intolerance.²

Study design for V-INITIATE: A 12-month, randomized, open-label, phase 3b study in patients with ASCVD (N=450) evaluated the efficacy and safety of early initiation with LEQVIO immediately upon failure to reach LDL-C <70 mg/dL on maximally tolerated statin vs usual care in a real-world setting.²

The co-primary end points were percentage change in LDL-C from baseline and statin discontinuation rate.²

Patients with ASCVD achieving LDL-C target^2‖

^‖Guideline-recommended LDL-C target was <70 mg/dL for patients with ASCVD.^4,6
¶73% of patients remained on statins only at Day 330.²

Limitations: Usual care did not reflect “best practice” with little use of guideline-recommended nonstatin therapy; therefore, a comparison of efficacy or safety of LEQVIO vs other nonstatin therapies cannot be made. LEQVIO use (n=10) was permitted in the usual care arm which may impact the effectiveness of comparisons. Although the study was designed to mimic clinical practice, statin discontinuation rates may not reflect the real world due to participants’ potential behavior change as a result of being part of a study. The open-label design has the potential for bias and may present difficulties in the interpretation of results.

Implementation of LEQVIO in a real-world setting: expert insights

Watch Dr Michael Koren, a clinical trial investigator for the V-INITIATE trial, discuss the importance of early LEQVIO use in patients with ASCVD (atherosclerotic cardiovascular disease), immediately after failure to reach LDL-C goals with statins.