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Abstract：
We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA).
The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months.
Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly.
PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.
The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months.
Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly.
PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.
摘要：
我们评估了前蛋白转化酶枯草杆菌蛋白酶/kexin9型抑制剂（PCSK9i）在接受LL药物和脂蛋白单采术（LA）治疗的杂合性家族性高胆固醇血症（HeFH）患者中的降脂（LL）作用。
PCSK9i治疗（evolocumab420mg/4周，alirocumab150毫克/2周，或alirocumab75mg/2周：9、6和2名患者，分别）在HeFH患者中开始（n=17；年龄35-69岁，10个男人,以前用他汀类药物+依泽替米贝±coleesevelam和LA治疗2-12年）。在LA会议之前和之后以及之前获得了血脂谱，改用PCSK9i治疗后1个月和2个月。PCSK9i治疗的持续时间为3至18个月。
中值总胆固醇（TC），低密度脂蛋白胆固醇（LDL-C），高密度脂蛋白胆固醇（HDL-C），LA之前的甘油三酯（TG）水平为268、198、46和126mg/dL，分别,并降低（在LA会议结束时）至117、50、40和51mg/dL，分别(TC的P<.001，所有其他比较的P=.001)。LA后时间平均LDL-C水平中位数为155（121，176；中位数[25，第75百分位数])mg/dL。中值TC,LDL-C,PCSK9i治疗前TG水平分别为269、190和127mg/dL，下降至152、100和95mg/dL，分别(分别为P=0.002、P<0.002和P<.03)。与LA后的时间平均LDL-C水平相比，PCSK9i治疗的稳定LDL-C水平显着降低（中位值：100vs155mg/dL；P=.008）。使用PCSK9i，从13名冠心病患者中，6例(46.1%)患者LDL-C<70mg/dL,2例患者（15.4%）LDL-C<100mg/dL。除2例患者每月继续进行一次外，所有患者均停止了脂蛋白单采术。
与HeFH患者LA后的短暂降低相比，PCSK9i可以随着时间的推移更一致地降低LDL-C。PCSK9i治疗可降低LA的频率。需要更大的试验来确定PCSK9i在先前接受LA的患者中的临床意义。
PCSK9i治疗（evolocumab420mg/4周，alirocumab150毫克/2周，或alirocumab75mg/2周：9、6和2名患者，分别）在HeFH患者中开始（n=17；年龄35-69岁，10个男人,以前用他汀类药物+依泽替米贝±coleesevelam和LA治疗2-12年）。在LA会议之前和之后以及之前获得了血脂谱，改用PCSK9i治疗后1个月和2个月。PCSK9i治疗的持续时间为3至18个月。
中值总胆固醇（TC），低密度脂蛋白胆固醇（LDL-C），高密度脂蛋白胆固醇（HDL-C），LA之前的甘油三酯（TG）水平为268、198、46和126mg/dL，分别,并降低（在LA会议结束时）至117、50、40和51mg/dL，分别(TC的P<.001，所有其他比较的P=.001)。LA后时间平均LDL-C水平中位数为155（121，176；中位数[25，第75百分位数])mg/dL。中值TC,LDL-C,PCSK9i治疗前TG水平分别为269、190和127mg/dL，下降至152、100和95mg/dL，分别(分别为P=0.002、P<0.002和P<.03)。与LA后的时间平均LDL-C水平相比，PCSK9i治疗的稳定LDL-C水平显着降低（中位值：100vs155mg/dL；P=.008）。使用PCSK9i，从13名冠心病患者中，6例(46.1%)患者LDL-C<70mg/dL,2例患者（15.4%）LDL-C<100mg/dL。除2例患者每月继续进行一次外，所有患者均停止了脂蛋白单采术。
与HeFH患者LA后的短暂降低相比，PCSK9i可以随着时间的推移更一致地降低LDL-C。PCSK9i治疗可降低LA的频率。需要更大的试验来确定PCSK9i在先前接受LA的患者中的临床意义。
