Pelacarsen and lipoprotein(a) apheresis in secondary prevention: the Lp(a)FRONTIERS APHERESIS trial.

The Lp(a)FRONTIERS APHERESIS trial investigated whether pelacarsen reduces the need for LA in patients from Germany with elevated Lp(a) and established cardiovascular disease (CVD).

Lp(a)FRONTIERS 血浆置换试验研究了Pelacarsen是否能减少德国升高的Lp(a)和已建立的心血管疾病（CVD）患者对LA的需求。

Methods

Adult patients with Lp(a) levels >60 mg/dl who had undergone ≥35 LA sessions in the prior year were randomized to receive pelacarsen 80 mg or placebo every 4 weeks for 52 weeks.

在过去的12个月里接受了≥35次脂蛋白清除（LA）治疗的成年患者，如果他们的Lp(a)水平>60 mg/dl，将被随机分配接受pelacarsen 80 mg或安慰剂，每4周一次，持续52周。

Weekly LA sessions were performed if the Lp(a) measurement from the prior visit was >60 mg/dL.

如果上一次访问的Lp(a)测量值>60 mg/dL，则执行每周一次的LA治疗。

The primary endpoint was the rate of performed LA sessions normalized to the weekly LA schedule (the number of actual LA sessions divided by the number of planned LA sessions during the 52-week period).

主要终点是根据每周计划的局部麻醉（LA）会话调整的完成LA会话的比率（52周期间实际进行的LA会话数除以计划的LA会话数）。

Secondary endpoints were time to LA avoidance (for ≥24 consecutive weeks) and total LA avoidance from week 12 to week 52.

次要终点是达到连续24周或以上避免局部麻醉（LA）的时间以及从第12周到第52周的总LA避免时间。

Results

Fifty-one patients were randomized (mean age 61.7 years, mean Lp(a) at baseline 85.4 mg/dL, and mean 44.0 LA sessions in the past 12 months), with 25 of 26 (96.2%) in the pelacarsen arm and 23 of 25 (92.0%) in the placebo arm completing the study.

共有51名患者被随机分配（平均年龄61.7岁，基线时平均Lp(a)水平为85.4 mg/dL，过去12个月平均进行44.0次LA治疗），其中26名患者中有25名（96.2%）在pelacarsen组和25名患者中有23名（92.0%）在安慰剂组完成了研究。

Baseline characteristics were generally balanced between treatment arms.

治疗组之间的基线特征总体上是平衡的。

Pelacarsen reduced the mean rates of LA (0.16 vs 0.93 in placebo, odds ratio 0.006, 95% confidence interval[CI] 0.003, 0.013; P < .0001) and substantially increased the hazard of achieving LA avoidance (hazard ratio: 88.3; P = .0014; median time to achieve LA avoidance: 6.1 weeks) and total LA avoidance (odds ratio: 163.2; P = .0005).

Pelacarsen 降低了平均低密度脂蛋白(LDL)水平（0.16 vs 0.93 对照组，比值比为0.006，95%置信区间[CI]为0.003, 0.013; P < .0001），显著增加了达到LDL目标值的危险（风险比：88.3; P = .0014; 达到LDL目标值的中位时间：6.1周）和完全达到LDL目标值的几率（比值比：163.2; P = .0005）。

The placebo-adjusted Lp(a) change from baseline at week 52 was -72% (95% CI: -79%, -61%; P < .0001).

与安慰剂相比，52周时基线Lp(a)的调整变化为-72%（95% CI: -79%, -61%; P < .0001）。

Treatment emergent adverse events were similar between arms, except for mostly mild injection site erythema (pelacarsen 38.5%; placebo 0%).

两组间治疗相关的不良事件相似，除了轻微的注射部位红斑（pelacarsen组为38.5%；安慰剂组为0%）。

Conclusions

Pelacarsen is a highly effective and well-tolerated Lp(a)-targeted therapy that substantially reduces the need for LA in patients with elevated Lp(a) and established CVD.

Pelacarsen是一种高效且耐受性良好的针对Lp(a)的治疗药物，能显著减少具有升高Lp(a)和已建立的CVD患者的LA需求。

CLINICALTRIALS.GOV, IDENTIFIER: NCT05305664.

临床试验注册号：NCT05305664。