Inclisiran Shows Good Toleration and Substantial LDL-C Reductions in Real-World Practice

Patients on background lipid-lowering therapy (LLT) receiving inclisiran (Leqvio; Novartis)—excluding those switching to the drug from a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor monoclonal antibody—experienced a 50% reduction in low-density lipoprotein cholesterol (LDL-C) and was well-tolerated in real-world practice, observations consistent with those in clinical trials, according to research published by investigators in Journal of Clinical Lipidology.¹

How Does Inclisiran Impact Patients in the Real World?

Inclisiran is an FDA-approved PCSK9 inhibitor in combination with a healthy diet and statin therapy to lower LDL-C in adults with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease (ASCVD), along with an indication as a monotherapy for LDL-C-lowering in adults with hypercholesterolemia. The small interfering RNA has been established in numerous clinical trials as a safe and effective option for reducing LDL-C, especially for individuals who have not achieved their cholesterol target goals with standard statin therapy.^2,3

Unique among other LLTs, inclisiran can be administered through a subcutaneous injection every 6 months by a health care professional following the first dose and a second dose at 3 months. Given this, it could be a more convenient option for patients seeking greater LDL-C reductions, with less strict adherence necessary. It is imperative to elucidate the real-world impacts of inclisiran on LDL-C in the United States given its potentially massive population benefit; however, literature is lacking on the subject. Prior research has suffered from small sample sizes, limited to utilizing pooling data from multiple lipid clinics rather than using data from a single site.^1,4

The current authors sought to report their 2-year real-world experience with inclisiran in an academic lipid clinic, both comparing LDL-C outcomes between patients on various types of LLTs other than statins at their beginning of inclisiran treatment and analyzing the real-world efficacy of inclisiran’s LDL-C reduction on patients switching from another LLT. The single-center, retrospective study enrolled patients prescribed inclisiran at the UCSD Health Advanced Lipid Disorders Clinic between March 2022 and November 2023.¹

Inclisiran Tolerated, Effective At Reducing LDL-C By 50%

After 120 individuals were recorded receiving at least 1 dose of inclisiran during the study period, 60 patients ultimately had at least 1 LDL-C measurement obtained 30 days or more after the first dose of inclisiran and were thus included in the study. A large portion (87%) of the cohort had a history of ASCVD, and nearly half of them (n = 29) were prescribed a statin at inclisiran initiation. Twelve patients switched from a different PCSK9 inhibitor monoclonal antibody to inclisiran within 1-month period prior to their first dose.¹

Throughout 134 days following the first dose of inclisiran to the first LDL-C follow-up measurement, patients received various numbers of inclisiran doses, ranging from 1 to 3. Importantly, most patients tolerated the injections well, with no observed serious adverse effects. For the 3 patients reporting mild adverse effects—including anxiety, fever, injection site pain, weakness, and fatigue—they had resolved by the time of their second injection.¹

LDL-C was found to have decreased by 38% mg/dL from baseline to the measurements taken at least 30 days following the patients’ first dose of inclisiran. For the 12 patients that switched from another PCSK9 to inclisiran, LDL-C increased 3.8% from baseline; however, for individuals who switched from a PCSK9 but were on another background LLT at inclisiran initiation had a nonstatistically significant decrease in LDL-C. When excluding all patients previously on PCSK9s, LDL-C decreased 45%, according to the investigators.¹

These results indicate clinically meaningful heterogeneity in real-world use of inclisiran when considering multiple poignant factors, including concomitant LLT use and whether a patient is switching from a different PCSK9 to inclisiran. Positively, inclisiran was well-tolerated, reflecting its strong safety signals from clinical trials. The investigators noted that 70% of the patients in this population reported past statin adverse effects or intolerance, which reflects the patients often treated with inclisiran in real-world clinical practice.¹

Pharmacists can know with confidence that inclisiran can induce meaningful LDL-C reductions, but with key factors such as past medication use impacting their efficacy. As trusted health care providers, pharmacists play a key role in ensuring proper adherence to inclisiran and in scheduling follow-up visits for patients.¹

REFERENCES

1. Mazdeyasnan D, Birs A, Chiou T, et al. Insights from a real-world experience with inclisiran at a large United States lipid clinic. J Clin Lip. 2025;19(4):812-818. doi:10.1016/j.jacl.2025.06.015

2. Ferruggia K. Inclisiran receives FDA approval for new indication to treat hypercholesterolemia. Pharmacy Times. Published August 1, 2025. Accessed September 25, 2025. https://www.pharmacytimes.com/view/inclisiran-receives-fda-approval-for-new-indication-to-treat-hypercholesterolemia

3. Halpern L. Inclisiran with LLT reduces LDL-C in hypercholesterolemia without inducing muscle pain. Pharmacy Times. Published September 9, 2025. Accessed September 25, 2025. https://www.pharmacytimes.com/view/inclisiran-with-llt-reduces-ldl-c-in-hypercholesterolemia-without-inducing-muscle-pain

4. Makhmudova U, Schatz U, Perakakis N, et al. High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany. Clin Res Cardiol. 2023;112(11):1639-1649. doi:10.1007/s00392-023-02247-8