PCSK9 Inhibitor Use and Outcomes Using Concomitant Lipid-Lowering Therapies in the Veterans Health Administration

Abstract

Background

Real-world data on use of PCSK9 inhibitors (PCSK9-Is), with or without statins and/or ezetimibe, and associated outcomes, can inform more effective prescribing. The objective was to evaluate clinical effectiveness and safety of PCSK9-Is within the Veterans Health Administration (VHA).

Methods

In this retrospective cohort study, we included Veterans who had at least one outpatient prescription for alirocumab and/or evolocumab filled within VHA between August 21, 2015, and September 30, 2020. Analyses included 4 mutually exclusive subgroups: PCSK9-I alone, PCSK9-I+statin, PCSK9-I+ezetimibe, and PCSK9-I+statin+ezetimibe subgroups. Primary outcomes included medication possession ratio, persistence, and low-density lipoprotein (LDL).

Results

Among Veterans in the analytical cohort (n = 2428), 36.2% were on PCSK9-I monotherapy; 24.0% received a PCSK9-I+statin; 27.4% were on a PCSK9-I+ezetimibe; and 12.4% received triple therapy, that is, PCSK9-I+statin+ezetimibe. The mean medication possession ratio (standard deviation [SD]) for PCSK9-I monotherapy was 83.8% (13.3) compared to 84.3% (11.2) with PCSK9-I+statin therapy, 87.1% (10.1) with PCSK9-I+ezetimibe therapy, and 85.8% (11.7) with triple therapy. The percentage of patients who discontinued PCSK9-I in the monotherapy subgroup was 12.3% vs 9.5%, 6.6%, and 7.4% in the concomitant statin, ezetimibe, and triple-therapy subgroups, respectively (p = .002 among the groups). Mean LDL level was greater in the PCSK9-I monotherapy subgroup (85.6 mg/dL) compared with the concomitant statin (66.5 mg/dL), ezetimibe (65.7 mg/dL), and triple-therapy subgroups (68.1 mg/dL).

Conclusions

Veterans showed good adherence and/or persistence with PCSK9-I regimens. On average, those receiving concomitant therapy with a statin and/or ezetimibe achieved significantly lower LDL levels.