PCSK9 inhibitor failure in a statin-intolerant FH patient with a novel LDLR variant: a case report

Background Approximately 3.8 million patients in China suffer from familial hypercholesterolemia (FH). Statins and PCSK9 inhibitors are recommended by guidelines as therapeutic agents. Nevertheless, cases in which patients demonstrate statin intolerance and an abnormal response to PCSK9 inhibitors present a significant challenge to the clinical treatment of the condition. Case presentation We report a 56-year-old Chinese female diagnosed with heterozygous familial hypercholesterolemia (HeFH). After taking simvastatin, she had elevated transaminases and creatine kinase levels, leading to a transition to PCSK9 inhibitor therapy. Unfortunately, the patient exhibited an absence of the desired response to three different PCSK9 inhibitors. A novel heterozygous missense variant in the LDLR gene (exon 11, c.1700C > T, p.Thr567Ile) was identified through related gene sequencing and genetic testing also revealed a heterozygous variant in the HTR7 gene. In light of the findings, she was treated with a combination of rosuvastatin and ezetimibe. This treatment resulted in the achievement of target lipid levels. During the follow - up, no adverse events were reported. Conclusion The study highlights that genetic testing should be considered for FH patients who experience failure with PCSK9 inhibitors, as novel LDLR variants may account for resistance and inform personalized treatment.