Effectiveness, Safety, and Adherence to Treatment of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Real Practice

Purpose: To evaluate the effectiveness, adverse reactions, and adherence to treatment of hypolipidemic inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9is) in a context of real clinical practice.

Methods: We present an observational, retrospective, descriptive, multicenter study of patients with hypercholesterolemia who began treatment with PCSK9is between January 2017 and December 2019, with a minimum treatment period of 3 months. The main variable we recorded was the frequency of cardiovascular events (cardiovascular death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina) in patients treated with PCSK9is. We recorded patient demographic characteristics and cardiovascular risk factors at onset of treatment as well as LDL-C levels and their reductions at 3, 6, 12, and 24 months. We calculated adherence to treatment and recorded the adverse reactions during treatment.

Findings: A total of 154 patients were studied, 64 (41.6%) of whom were treated with alirocumab and 90 (58.4%) with evolocumab. The initial dose of alirocumab was 75 mg every 14 days in 48 patients (75%) and 150 mg eery 14 days in 16 (25%). All patients who in the evolocumab group received a dose of 140 mg every 14 days. The mean (SD) basal LDL-C level was 159.6 (50.1) mg/dL, the level at 3 months was 87.9 (49.9) mg/dL (mean [SD] decrease, 44.5% [28.2%]), the level at 6 months was 86.7 (49.2) mg/dL (mean [SD] decrease, 46.3% [25.6%]), and the level at 12 months was 80.5 (41.4) (mean [SD] decrease, 48.9% [23.0%]). These values were maintained at 24 months (mean [SD], 80.3 [41.8] mg/dL; mean [SD] decrease, 47.9% [27.8%]). The percentage decrease of LDL-C for both drugs was approximately 50%, which was maintained until 24 months after treatment. Six patients (3.9%) presented with some cardiovascular event: acute myocardial infarction (2 [1.3%]), stroke (1 [0.65%]), coronary revascularization (1 [0.65%]), and hospitalization for unstable angina (2 [1.3%]). We did not see any adverse reactions related to PCSK9i treatment in 76.5% of patients. In the first 6 months, adherence to treatment with PCSK9is, measured as the possession ratio, was a mean (SD) of 99.4% (3.9%). In the rest of the study period (6-24 months), the mean (SD) adherence to treatment was 99.2% (4.7%).

Implications: The frequency of cardiovascular events in patients treated with PCSK9is was low and occurred despite adequate adherence to treatment (100% possession ratio) with PCSK9is and concomitant treatment with other hypolipidemics. The effectiveness of PCSK9is is similar to that referred to in other published studies with PCSK9is, and this was maintained in the long term (24 months) with few adverse events, all of which were mild.