Real-World Insights Into Evolocumab Use in Patients With Hyperlipidemia: Canadian Analysis From the ZERBINI Study

Abstract

Background: The 2021 Canadian Cardiovascular Society guidelines recommend proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy in patients with atherosclerotic cardiovascular disease whose low-density lipoprotein cholesterol (LDL-C) concentration remains ≥ 1.8 mmol/L despite maximally tolerated statin therapy. This retrospective and prospective observational study characterizes Canadian patients treated with evolocumab and describes its effectiveness and safety.

Methods: Between August 2017 and July 2019, a total of 131 patients initiated on evolocumab therapy were enrolled at 15 sites in Canada. Data were extracted from medical records every 3 months between 6 months prior to, and for 12 months following evolocumab therapy initiation, until July 6, 2020. Baseline and prospectively collected data are reported as available.

Results: A total of 131 patients were enrolled (59.5% male; mean age [standard deviation (SD)] 64.7 ± 10.6 years), most with a diagnosis of atherosclerotic cardiovascular disease and/or familial hypercholesterolemia (93.4%). Mean (± SD) LDL-C concentration at baseline was 3.7 (± 1.7) mmol/L (n = 119), with 58.0% of patients receiving a statin (36.6% high intensity). Mean (± SD) LDL-C concentration after evolocumab treatment was 1.6 (± 1.0) mmol/L (n = 120), representing a 58.7% decrease from baseline (n = 109). This level remained stable over 12 months. An LDL-C concentration < 1.8 mmol/L was achieved by 77.5% of patients. Persistence was 92%, and no serious treatment-emergent adverse events were reported.

Conclusions: These findings provide real-world evidence of guideline-recommended initiation of evolocumab therapy, as well as confirmation of its effectiveness and safety in a Canadian population. Evolocumab therapy can address a healthcare gap in the management of dyslipidemia, by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.

Graphical abstract

Figure 1

Low-density lipoprotein (LDL-C) concentrations at baseline and post-evolocumab therapy initiation (N = 109. Data represent patients with an LDL-C measurement at baseline (measured within 6 months prior to initiation of evolocumab therapy) and their last LDL-C measurement post-evolocumab therapy initiation. Results were similar for patients on evolocumab monotherapy vs those on evolocumab plus lipid-lowering therapy (mean 56.5% vs 56.9% reduction). Values are means ± standard deviation accompanied by percent change from baseline.

Figure 2

Distribution of percent change from baseline to average low-density lipoprotein cholesterol (LDL-C) post-evolocumab therapy initiation (N = 109). Data represent patients with an LDL-C measurement at baseline (measured within 6 months prior to initiation of evolocumab therapy) and their last LDL-C measurement post-evolocumab therapy initiation.

Figure 3

Low-density lipoprotein cholesterol (LDL-C) concentrations over time in patients without missing LDL-C measurements (N = 70). Data represent patients with a baseline LDL-C measurement and subsequent LDL-C measurement within 1-6 months and 7-12 months post-evolocumab therapy initiation. Values are mean ± standard deviation. ^†The last LDL-C measurement within 6 months prior to initiation of evolocumab therapy.

Figure 4

Lipid-lowering therapies over the study period. ∗Statin intensity was defined based on the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.^†Over the course of the trial, 7 patients discontinued statins after initiation of evolocumab therapy; 3 patients up-titrated and 1 patient down-titrated the statin dose; 7 patients discontinued ezetimibe; 5 of those 7 patients were on a background statin that was not discontinued. ^‡The last LDL-C measured within 6 months prior to initiation of evolocumab was regarded as the baseline LDL-C.