Safety aspects and side effects of the novel lipid-lowering PCSK9 inhibitors evolocumab/alirozumab in atherosclerotic patients with familial hypercholesterolemia under lipid apheresis

Purpose The present study was intended to analyze potential side effects of a PCSK9 inhibitor therapy. Methods The study includes 37 patients (mean age 63.6±9.2 (41-81) years, 48.6% females) presenting with progressive atherosclerosis and familial hypercholesterolemia at our outpatient department or undergoing routine lipid apheresis therapy who fulfilled the indication for PCSK9 inhibitor therapy (insufficient LDL reduction under statin ezetimibe therapy or with statin ezetimibe intolerance). After onset of therapy, patients underwent regular follow-ups including a detailed questionnaire regarding the side effects of drug therapy. Results Of 19 patients undergoing alirocumab therapy 31.6% (n=6) received a double dosis every four weeks, the other 13 patients the standard dosis every two weeks. 18 patients were administered evolocumab every two weeks. 43.2% (n=16) of all patients reported on side effects (63 events, mean 3.9 per patient). Most frequent side effects were fatigue (n=8), myalgia (n=7), arthralgia (n=6), memory and cognitive impairment, restlessness, dizziness, and nausea (n=5 each). Furthermore, flu-like symptoms (n=3), retarded reaction (n=3), cutaneous irritation at the injection site (n=2), exanthema (n=2), and inflammation of the upper airways (n=2) were also reported. Alirocumab (53.3%, n=10) was associated with a higher incidence of side effects than evolocumab (33.3%, n=6). Under alirocumab myalgia and fatigue were observed most frequently, under evolucumab dizziness and memory disorders. Standard dosis of alirocumab every 2 weeks was associated with lower side effects than the double dosis every 4 weeks (46.1 vs. 66.7%). Due to significant myalgia under alirocumab (300 mg/4w), a dosis reduction was mandator in one patient. In another patient, discontinuation of alirocumab therapy was indicated as she developed a severe depressive disorder. Conclusion Therapy-induced side effects under PCSK9 inhibitor therapy (alirocumab or evolocumab) have been reported by 43.2% of our patients. Most common side effects were fatigue, myalgia, arthralgia followed by neurocognitive disorders such as memory and concentration disorders. The most important complications reported in randomized studies such as local reaction at the injection site (redness and swelling) as well as flu-like symptoms were less frequently observed. Alirocumab was associated with a higher incidence of side effects than evolocumab. A more detailed data acquisition should focus on the dosage increase to prolong the application intervals.