Spitthöver Ralf, Röseler Tilmann, Julius Ulrich, Heigl Franz, Schettler Volker J J, Kühn Ralf, Leebmann Josef, Raabe Andrea, Knittel Markus, Schürfeld Carsten, Moesenthin Michael, Bernhardt Wanja M, Röseler Eberhard, Ketteler Markus, Heibges Andreas, Klingel Reinhard
Dialysis and Lipid Center North Rhine, Essen, Germany.
Center for Nephrology, Hypertension, and Metabolic Diseases, Hannover, Germany.
J Clin Apher. 2019 Aug;34(4):423-433. doi: 10.1002/jca.21695. Epub 2019 Feb 28.
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.
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.
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%).
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.
在开始慢性脂蛋白分离术（LA）的最后一步之前，使用单克隆抗体抑制前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）补充了降脂治疗（LLT）的手段。关于在使用PCSK9抗体强化LLT后开始慢性LA或在长期LA期间开始PCSK9抗体治疗的患者的数据很少。
在本研究中，连续确定了110例因高胆固醇血症或合并脂蛋白（a）-高脂蛋白血症而患有已确诊动脉粥样硬化性心血管疾病（ASCVD）的患者，这些患者在常规护理期间首次接受PCSK9抗体治疗。
在开始LA或PCSK9抗体治疗之前，平均低密度脂蛋白胆固醇（LDL-C）浓度为5.3±2.6 mmol/L（205±102 mg/dL）。由于已确诊ASCVD，所有患者的风险调整后LDL-C目标值均<1.8 mmol/L（<70 mg/dL）。使用PCSK9抗体使总体达到LDL-C目标浓度的患者比例增加了41.8%。35例患者（31.8%）报告了与PCSK9抗体药物相关的治疗出现的不良事件（TEAE）。25例患者（22.7%）因TEAE停用PCSK9抗体治疗。
最后，55.5%的患者以个体优化的治疗频率接受了PCSK9抗体治疗和LA的联合治疗，使54.1%的患者实现目标的比例增加。在这项真实世界研究中，约18.1%的慢性LA患者终止了LA治疗。迄今为止预防ASCVD进展的长期LA治疗的终止需要仔细的个体风险评估，不能根据LDL-C降低的一般标准推荐。
