Abstract：
OBJECTIVE: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting.
RESULTS: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016).
CONCLUSIONS: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH.
Contemporary real-world data from the Italian cohort of patients affected by homozygous familial hypercholesterolaemia demonstrated that the addition of novel, low-density lipoprotein receptor (LDLR)-independent medications to conventional therapies allowed the achievement of unprecedented low-density lipoprotein cholesterol (LDL-C) values with a trend towards a reduction of cardiovascular risk.
RESULTS: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016).
CONCLUSIONS: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH.
Contemporary real-world data from the Italian cohort of patients affected by homozygous familial hypercholesterolaemia demonstrated that the addition of novel, low-density lipoprotein receptor (LDLR)-independent medications to conventional therapies allowed the achievement of unprecedented low-density lipoprotein cholesterol (LDL-C) values with a trend towards a reduction of cardiovascular risk.
摘要：
目的：新型降脂疗法（LLTs）的应用显著改变了纯合型家族性高胆固醇血症（HoFH）的临床治疗。在真实世界的临床环境中，在139名HoFH患者的队列中评估了这些进展的影响。
结果：139例HoFH患者的临床特征，以及基线和中位随访5年后的LLTs和低密度脂蛋白胆固醇（LDL-C）水平的信息，我们从纳入LIPid转运障碍意大利GeNetic网络-家族性高胆固醇血症(LIPIGEN-FH)注册的患者记录中进行回顾性检索.比较基线前后随访期间主要动脉粥样硬化心血管事件（MACE-plus）的年发生率。此外,将无MACE+的终身生存率与历史LIPIGENHoFH队列的生存率进行了比较.在基线,LDL-C水平为332±138mg/dL。随访期间,LLT的效力得到了增强，在最后一次访问中，15.8%的患者采用四联疗法。始终如一，LDL-C降至124mg/dL的平均值，相当于降低58.3%（Pt<0.001），在接受前蛋白转化酶枯草杆菌蛋白酶/kexin9型抑制剂和洛米他必特和/或evinacumab作为附加疗法的患者中达到最低值(~90mg/dL)。5年随访中的平均年MACE+率显著低于基线访视前5年观察到的(21.7vs.56.5/1000患者/年；P=0.0016）。
结论：我们的研究结果表明，新型和常规LLTs的组合显着改善了LDL-C控制，表明HoFH患者的心血管预后更好。总的来说,这些结果提倡集约使用，多药LLTs有效管理HoFH。
来自意大利纯合子家族性高胆固醇血症患者队列的当代真实世界数据表明，传统疗法的低密度脂蛋白受体(LDLR)非依赖性药物使得低密度脂蛋白胆固醇(LDL-C)值达到了前所未有的水平,并有降低心血管风险的趋势.
结果：139例HoFH患者的临床特征，以及基线和中位随访5年后的LLTs和低密度脂蛋白胆固醇（LDL-C）水平的信息，我们从纳入LIPid转运障碍意大利GeNetic网络-家族性高胆固醇血症(LIPIGEN-FH)注册的患者记录中进行回顾性检索.比较基线前后随访期间主要动脉粥样硬化心血管事件（MACE-plus）的年发生率。此外,将无MACE+的终身生存率与历史LIPIGENHoFH队列的生存率进行了比较.在基线,LDL-C水平为332±138mg/dL。随访期间,LLT的效力得到了增强，在最后一次访问中，15.8%的患者采用四联疗法。始终如一，LDL-C降至124mg/dL的平均值，相当于降低58.3%（Pt<0.001），在接受前蛋白转化酶枯草杆菌蛋白酶/kexin9型抑制剂和洛米他必特和/或evinacumab作为附加疗法的患者中达到最低值(~90mg/dL)。5年随访中的平均年MACE+率显著低于基线访视前5年观察到的(21.7vs.56.5/1000患者/年；P=0.0016）。
结论：我们的研究结果表明，新型和常规LLTs的组合显着改善了LDL-C控制，表明HoFH患者的心血管预后更好。总的来说,这些结果提倡集约使用，多药LLTs有效管理HoFH。
来自意大利纯合子家族性高胆固醇血症患者队列的当代真实世界数据表明，传统疗法的低密度脂蛋白受体(LDLR)非依赖性药物使得低密度脂蛋白胆固醇(LDL-C)值达到了前所未有的水平,并有降低心血管风险的趋势.
