UTILIZATION AND EFFECTIVENESS OF PCSK9 INHIBITORS IN IMPROVING LIPID PROFILE IN ROUTINE CLINICAL PRACTICE

OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) are a new class of drugs that have been shown to further reduce low-density lipoprotein cholesterol (LDL-C) by 50-70% against various background lipid-lowering therapies. We aimed to assess the use of two PCSK9-I, alirocumab and evolocumab, and compare their effectiveness in improving lipid profile to statins in routine practice. METHODS: Using a large U.S. administrative database, OptumLabs Data Warehouse, with linked laboratory data, we identified 798 patients who initiated PCSK9-I between 8/1/2015-7/31/2016. Among patients with lipid measurements at both baseline and follow up, we propensity score matched patients treated with PCKS9-I (alone or with statins) to those treated with statins (alone or with other non-PCKS9-I lipid lowering drugs). Patients were balanced on 40 baseline characteristics, including socio-demographics, lipid levels, comorbidities, prior lipid lowering treatment and other medication use. We used linear regression to compare the absolute change and percentage change of lipid levels. RESULTS: The mean LDL-C of PCSK9-I users was 122.2 mg/dL prior to the initiation of PCSK9-I, similar to those observed in the Phase III trials. However, over one third of the patients had LDL-C < 100 mg/dL. Most users (72%) used non-PCKS9-I cholesterol lowering drugs (mostly statins) at baseline. In the matched cohort (N=166), over an average of 10 weeks, PCSK9-I were associated with a greater reduction in LDL-C (-14.0 mg/dL, p=0.02; -12%, p=0.01) and non-high-density lipoprotein cholesterol (-15.3 mg/dL, p=0.03; -9.4%, p=0.01) in comparison to statins. Neither drugs significantly reduced LDL-C in patients with LDL-C < 100 mg/dL. CONCLUSIONS: PCSK9-I were commonly prescribed for patients who either had low LDL-C or already achieved low LDL-C on statins, which is a group largely excluded from clinical trials. Consistent with trials, PCSK9-I demonstrated a greater reduction in LDL-C than statins in routine clinical practice, but this benefit was not seen in patients with low LDL-C.