Treatment persistence, lipid lowering, and 3-year clinical outcomes in patients at very high cardiovascular risk on PCSK9 monoclonal antibodies

TL;DR

This study shows that PCSK9 monoclonal antibodies help patients with high cardiovascular risk achieve better cholesterol control and fewer hospitalizations over three years.

Contribution

The study provides real-world evidence on the long-term effectiveness and persistence of PCSK9-mAb therapy in high-risk patients.

Findings

PCSK9-mAb users achieved lower LDL-C levels and higher target attainment compared to non-users.

Patients on PCSK9-mAb had significantly lower hospitalization rates for cardiovascular events.

Persistence with PCSK9-mAb therapy was high, with statin intolerance linked to higher discontinuation rates.

Abstract

In a cohort of patients with dyslipidemia at very high cardiovascular risk, we investigated differences in LDL-C lipid target achievement, clinical outcomes, and persistence rates between users and non-users of PCSK9 monoclonal antibodies (PCSK9-mAb) over a 3-year observation period. The prospective, multi-center observational study included 1695 patients with dyslipidemia. Eligible patients were adults with familial or non-familial hypercholesterolemia, mixed dyslipidemia, or other therapy-refractory lipid disorders in line with the G-BA reimbursement regulations. Treatment decisions, including PCSK9-mAb administration, were made at the discretion of the treating physician. At baseline, 804 (47.4%) patients received PCSK9-mAb therapy, and 891 (52.5%) did not. There were 42 (4.7%) new PCSK9-mAb receivers during the follow-up. Median propensity-score adjusted LDL-C levels in PCSK9-mAb non-receivers decreased over time from 106.0 to 68.4 mg/dL. LDL-C in PCSK9-mAb receivers dropped from 112.5 mg/dL at baseline to 58.0 mg/dL at 3 years, consistently outperforming non-receivers. Target LDL-C goal attainment (< 55mg/dL) after 3 years was higher in the PCSK9-mAb group (43.2% vs. 34.5%). Persistence with PCSK9-mAb therapy over 3 years since treatment initiation was high (91.5%). Higher discontinuation rates of PCSK9-mAb were associated with baseline statin intolerance (HR = 2.3, p = 0.012). The use of PCSK9-mAb was associated with numerically fewer cardiovascular events (9.3 versus 15.7 per 100 patient-years, p not significant) and lower hospitalization rates due to cardiovascular events compared to non-users (6.3 versus 12.4 per 100 patient years, p = 0.001). This study underscores the real-world efficacy and safety of PCSK9-mAb therapy in achieving sustained LDL-C reduction. Identifier: Clinicaltrials.gov NCT03110432.

The online version contains supplementary material available at 10.1007/s00392-025-02719-z.

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