Real-World Data Show Leqvio's Effectiveness in Reducing LDL-C in Patients With ASCVD

New findings from the V-INITIATE trial were presented at the 2024 American College of Cardiology's Annual Scientific Session & Expo and published in the Journal of the American College of Cardiology, demonstrating the substantial impact of inclisiran (Leqvio) on lowering low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD).¹

Low-density lipoprotein cholesterol | Image credit: LASZLO – stock.adobe.com

According to a news release from Novartis, the study underscores the significance of early addition of twice-yearly inclisiran to maximally tolerated statin therapy, before ezetimibe, as a means to achieve better LDL-C management in patients with ASCVD who struggle to reach their goals with statins alone.²

Michael Koren, MD, medical director and CEO of Jacksonville Center for Clinical Research and lead investigator of the trial, highlighted the critical need to address the challenge of inadequate LDL-C control in these patients.

“V-INITIATE evaluated a solution to the important challenge seen in clinical practice of too many patients with ASCVD not achieving guideline-recommended LDL-C goal on statins alone and effective non-statin therapies being markedly underutilized,” Koren said in the news release.² “Given the urgent need to more aggressively manage LDL-C, the results from V-INITIATE show that when added earlier in the treatment continuum, the structured use of effective non-statin therapies like Leqvio can significantly reduce LDL-C for ASCVD patients who are struggling to reach or maintain their LDL-C goal.”

The findings of the V-INITIATE phase 3b study indicate that initiating inclisiran immediately in patients with atherosclerotic cardiovascular disease (ASCVD) who have not achieved LDL-C levels <70 mg/dL leads to significant reductions in LDL-C. This prospective study, conducted across 45 sites in the US, involved 450 adult patients with elevated LDL-C levels randomized to receive either usual care or usual care plus immediate inclisiran initiation at 0, 90, and 270 days. Laboratory assessments were performed at 0, 90, 180, 270 and 330 days, and the mean baseline LDL-C was 97.4 mg/dL.

Results showed a substantial 60% reduction in LDL-C from baseline to day 330 in the inclisiran first group compared with a mere 7% reduction in the usual care group, meeting the primary endpoint of the study. Additionally, a higher proportion of patients in the inclisiran first group achieved the target LDL-C level of <70 mg/dL (81.8%) compared with the usual care group (22.2%), highlighting the efficacy of inclisiran in achieving LDL-C goals. However, patients in the inclisiran first group experienced more injection-site treatment-emergent adverse events and withdrawal due to treatment-emergent adverse events compared to the usual care group, although overall adverse event rates were similar between the 2 groups.

“The data from V-INITIATE illustrate that earlier initiation of innovative non-statin therapies, like Leqvio, presents a real opportunity to do better for ASCVD patients and improve the way we approach LDL-C lowering,” said David Soergel, MD, global head of cardiovascular, renal and metabolic drug development at Novartis.² “This study adds data from a real-world setting to the growing body of evidence for Leqvio being generated through our robust VictORION program, and further reinforces the clinical value of this twice-yearly HCP-administered therapy.”

The V-INITIATE trial is part of the comprehensive VictORION clinical program for inclisiran, which encompasses over 30 trials and involves more than 60,000 patients across 50 countries worldwide. This program aims to build upon the existing evidence of inclisiran’s efficacy in reducing LDL-C levels by conducting randomized clinical trials, implementation research, and real-world studies. Major trials within the program—such as ORION-4 for secondary prevention and V-2-PREVENT for high-risk primary prevention—are planned to further explore inclisiran’s potential benefits on cardiovascular outcomes.

ASCVD encompasses various conditions triggered by the accumulation of plaques within artery walls, primarily consisting of LDL-C. The gradual buildup of LDL-C correlates with plaque growth, increasing the risk of cardiovascular events like heart attacks and strokes. Responsible for 85% of cardiovascular disease-related deaths, ASCVD is the leading cause of mortality in the European Union, and its impact in the US surpasses that of any other chronic condition. Conditions such as diabetes and familial hypercholesterolemia are considered ASCVD risk-equivalents due to their comparable risk of cardiovascular events.²

References

1. Koren MJ, Rodriguez F, East C, et al. An Inclisiran First Strategy vs Usual Care in Patients with Atherosclerosis. J Am Coll Cardiol. Published online April 6, 2024. doi:10.1016/j.jacc.2024.03.382
2. New Novartis data show early addition of twice-yearly Leqvio (inclisiran) following maximally tolerated statin therapy significantly reduces LDL-C in ASCVD patients in real-world setting. News release. Novartis. April 6, 2024. Accessed April 11, 2024. https://www.novartis.com/news/media-releases/new-novartis-data-show-early-addition-twice-yearly-leqvio-inclisiran-following-maximally-tolerated-statin-therapy-significantly-reduces-ldl-c-ascvd-patients-real-world-setting