Real-World Low-Density Lipoprotein Cholesterol Control After Transitioning From Evolocumab to Inclisiran

Abstract

Background

Inclisiran is a siRNA therapy that provides sustained reduction in low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing, but real-world data after switching from PCSK9 monoclonal antibodies remain limited.

Methods and Results

We retrospectively analyzed 32 patients with coronary artery disease who transitioned from evolocumab to inclisiran. Median LDL-C was 27.0 mg/dL at baseline and remained stable at 3, 6, and 9 months (29.0, 30.5, and 29.5 mg/dL). Eight patients (25%) exceeded the LDL-C target (<70 mg/dL) at least once, more frequently among those with heterozygous familial hypercholesterolemia. Discontinuation occurred in 12.5%.

Conclusions

Switching to inclisiran generally maintained LDL-C levels, although patients with familial hypercholesterolemia may require closer monitoring.

Central Figure.

PCSK9 monoclonal antibodies reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in atherosclerotic cardiovascular disease.¹ Inclisiran, a siRNA therapy, suppresses hepatic PCSK9 synthesis with twice-yearly dosing.² However, real-world data on LDL-C control after switching to inclisiran from monoclonal antibodies remain limited. We evaluated LDL-C control and treatment continuity in clinical practice after switching from evolocumab to inclisiran.

Methods

We retrospectively analyzed 33 patients with coronary artery disease who switched from evolocumab to inclisiran at Urasoe General Hospital between November 2023 and June 2024. One patient without follow-up LDL-C data was excluded, leaving 32 patients.

Median evolocumab treatment duration was 330 days (interquartile range [IQR] 198–425). The interval between the last evolocumab dose and the first inclisiran dose was 0 days (IQR 0–0), except for 1 patient (40 days).

LDL-C was measured at baseline and at 3, 6, and 9 months. Missing data occurred in 6%, 25%, and 13% of measurements at these time points. The LDL-C target was <70 mg/dL. Familial hypercholesterolemia (FH) was diagnosed according to Japanese Atherosclerosis Society criteria. Continuous variables are expressed as medians with IQRs; analyses were primarily descriptive given the small sample size.

Results

Among the 32 patients, median age was 69.5 years (IQR 60.8–78.3) and 75% were men. Heterozygous FH was present in 22% of patients. Statins were used in all but 1 patient, and 45% received ezetimibe. After switching, statin dose escalation occurred in 1 patient and ezetimibe was initiated in 1 patient.

Median LDL-C remained stable following the transition (Figure). LDL-C was 27.0 mg/dL (IQR 15.0–47.5) at baseline, 29.0 mg/dL (21.0–58.8) at 3 months, 30.5 mg/dL (26.0–61.5) at 6 months, and 29.5 mg/dL (22.3–56.3) at 9 months.

Figure.

Longitudinal changes in low-density lipoprotein cholesterol (LDL-C) after switching from evolocumab to inclisiran. Box-and-whisker plots showing LDL-C at baseline and at 3, 6, and 9 months after switching therapy. The box represents the interquartile range, the horizontal line indicates the median, and whiskers denote minimum and maximum values. The dashed line represents the LDL-C target of 70 mg/dL. Sample sizes were baseline (n=32), 3 months (n=30), 6 months (n=24), and 9 months (n=28).

Eight patients (25%) exceeded the LDL-C target at least once during follow-up. Among them, median LDL-C was 77.0 mg/dL (IQR 65.0–98.0) at 6 months and 70.0 mg/dL (65.0–86.0) at 9 months.

Inclisiran was discontinued in 4 patients (12.5%) during follow-up because of transfer of care (n=2), non-adherence (n=1), or insufficient LDL-C reduction (n=1).

Discussion

In this real-world cohort, switching from evolocumab to inclisiran was associated with maintenance of LDL-C levels over 9 months. The minimal treatment gap (i.e., most patients received inclisiran on the same day as their final evolocumab dose) likely contributed to stable lipid control.

Approximately 25% of patients exceeded the LDL-C target at least once during follow-up, and FH was more common in these individuals. Clinical trials have demonstrated inclisiran efficacy in heterozygous FH,³ although the LDL-C reduction may be smaller than with monoclonal antibody therapy in some analyses.⁴ Real-world studies have also reported modest LDL-C increases after switching therapy.⁵ Given the descriptive nature of this study, these observations should be considered hypothesis-generating.

Treatment persistence was relatively high, with 87.5% of patients continuing inclisiran at 9 months. The twice-yearly dosing schedule may reduce treatment burden, particularly for patients who have difficulty with self-injection.

Study Limitations

Single-center retrospective design, small sample size, and incomplete follow-up data. No comparator group continuing evolocumab was included, and clinical outcomes were not assessed. Therefore, findings should be interpreted as exploratory.

Conflict of Interest

The authors declare no conflicts of interest.

IRB Information

Approved by the Institutional Review Board of Urasoe General Hospital (Reference No. 2025-018).

Data Availability Statement

De-identified aggregate data on patient demographics, lipid profiles, PCSK9 therapy patterns, and clinical outcomes will be shared. The study protocol and opt-out disclosure document may be available upon request. Data will be accessible after publication and retained per institutional policy. Access is limited to researchers with a valid proposal approved by the IRB, for purposes consistent with the original study. Secondary analyses on lipid management and clinical outcomes are permitted. Data will be shared via secure institutional channels following execution of a data use agreement.