Inclisiran in addition to statin therapy lowers lipoprotein(a) and improves one-year outcomes in young patients with familial hypercholesterolemia and coronary artery disease

Background / Introduction

Residual cardiovascular risk in patients with familial hypercholesterolemia (FH) and prior acute coronary syndrome (ACS) may be driven in part by elevated lipoprotein(a) [Lp(a)], which is not substantially reduced by statin therapy alone. Inclisiran, a small interfering RNA targeting PCSK9, has been shown to lower LDL-C and Lp(a).

Purpose

To evaluate the effect of inclisiran added to statin therapy versus statin monotherapy on LDL-C, Lp(a), and one-year clinical outcomes in young patients with FH and established ischemic heart disease.

Methods

We included 104 patients aged 40–55 years with prior ACS, arterial hypertension, and dyslipidemia (LDL-C >5 mmol/L, total cholesterol >7.5 mmol/L). Patients were assigned to:

Statin monotherapy (atorvastatin 40 mg, n=58)

Combined statin (atorvastatin 40 mg) + inclisiran therapy (n=46)

Baseline and follow-up lipid profiles, including LDL-C and Lp(a), were collected during 2025. Clinical outcomes were prospectively monitored over one year.

Results

At baseline, total cholesterol reached a maximum of 14.1 mmol/L and LDL-C 9.3 mmol/L. Women had higher baseline Lp(a) levels compared with men.

After 12 months, statin monotherapy achieved LDL-C <3.0 mmol/L, whereas combined therapy achieved LDL-C <1.9 mmol/L. Combined therapy resulted in an approximately 40% reduction in Lp(a), with more pronounced reductions in women. No meaningful Lp(a) change was observed in the statin monotherapy group.

During one-year follow-up, no patient in either group experienced recurrent ACS, while five patients in the statin monotherapy group were hospitalized for unstable angina.

Conclusion

In young patients with FH and prior ACS, statin therapy effectively lowers LDL-C but does not substantially reduce Lp(a). Addition of inclisiran provides superior lipid control, including significant Lp(a) reduction—particularly in women—and is associated with fewer ischemic events over one-year follow-up. These results support combined therapy as an effective secondary prevention strategy in high-risk patients.