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Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid‐lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long‐term LA. Patients and Methods In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)‐hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutively identified. Results Mean LDL‐C concentration prior to initiation of LA or PCSK9 antibody treatment was 5.3 ± 2.6 mmol/L (205 ± 102 mg/dL). Due to established ASCVD, the risk‐adjusted LDL‐C target value was <1.8 mmol/L (<70 mg/dL) in all patients. Use of PCSK9 antibodies increased the proportion of patients attaining the LDL‐C target concentration by 41.8% overall. Treatment emergent adverse events (TEAE) associated with PCSK9 antibody medication were reported in 35 patients (31.8%). Discontinuation of PCSK9 antibody therapy due to TEAEs occurred in 25 patients (22.7%). Conclusion Finally, 55.5% of patients received a combination of PCSK9 antibody therapy and LA at individually optimized treatment frequencies resulting in an increase of target attainment in 54.1% of patients. About 18.1% of chronic LA patients terminated LA treatment in this real‐world study. The termination of long‐term LA therapy, which has hitherto prevented the progression of ASCVD, requires careful individual risk assessment and cannot be recommended by the general criteria of LDL‐C reduction.

The mitochondrial (mt) 3243 DNA mutation is an underlying cause of maternally inherited diabetes and deafness (MIDD) syndrome and the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We report an affected German MIDD pedigree with maternal lineage over three generations. The index patient, her mother, her maternal aunt and her maternal grandmother all suffered from diabetes and premature hearing loss and were positive on testing for the mt 3243 DNA mutation. The 27-year-old index patient had a history of grand mal seizures. As sequela of abdominal ultrasound and confirmed by magnetic resonance cholangio-pancreaticography, she was diagnosed with chronic pancreatitis with pancreatic calcifications and pancreatic duct dilation, although she was completely asymptomatic and with no signs of steatorrhoea. She did not have gallstones and the common bile duct was normal. A possible etiopathogenic pathway for pancreatitis could be a suppressive effect of the mt 3243 mutation on the oxidative phosphorylation in affected mitochondria. Although pancreatitis and pancreatic dysfunction in association with the mt 3243 mutation, especially in patients with comorbidity of MELAS and diabetes, has previously been described as a rare manifestation, this case is specific because of the discrepancy of advanced morphological pancreatic alterations and complete lack of pancreatogenic symptoms.

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Next to drug therapy, regular LA is an essential component of LLT for approaching LDL-C targets in children with hoFH or c-hetFH, which was successful only in a minority of children. Progression of CVD morbidity and resulting mortality remain unresolved issues. Early and intensified multimodal LLT guided by risk factors beyond LDL-C concentration is needed to improve outcome.