Vogt Anja
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstraße 1, 80336, Munich, Germany.
Clin Res Cardiol Suppl. 2019 Apr;14(Suppl 1):51-56. doi: 10.1007/s11789-019-00096-2.
Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD) and Lp(a) is acknowledged as a risk factor to be included in risk assessment. The established lipid-modifying medical therapies do not lower Lp(a) except niacin but no data of endpoint trials are available. Of the new lipid-modifying drugs a few have some impact on Lp(a). Whether the Lp(a) lowering effect contributes to the reduction of CVD events would have to be shown in Lp(a) dedicated trials. None of the available agents is indicated to lower Lp(a). Lipoprotein apheresis lowers levels of Lp(a) significantly by >60% per treatment. Trial data and data of the German Lipoprotein Apheresis Registry show that regular apheresis reduces cardiovascular events. The Apo(a) antisense oligonucleotide is the only approach to specifically lower Lp(a). The IONIS-APO(a) phase 1 and 2 trials showed very substantial decreases of Lp(a) and good tolerability. The hepatospecific variant IONIS-APO(a)-L is 30 times more potent. The results of the IONIS-APO(a)-L phase 2 trial were presented recently. The highest dosages reduced Lp(a) by 72 and 80%; in about 81 and 98% Lp(a) levels <50 mg/dl were achieved. Tolerability and safety were confirmed, whereby injection site reactions were the most common side effects. This raises hope that the planned phase 3 trial will reproduce these findings and show a reduction of cardiovascular events.
脂蛋白(a)[Lp(a)]水平升高会增加早期和严重心血管疾病（CVD）的风险，Lp(a)被公认为是风险评估中应纳入的一个风险因素。除烟酸外，现有的调脂药物均不能降低Lp(a)，但尚无终点试验数据。在新型调脂药物中，有几种对Lp(a)有一定影响。Lp(a)降低效应是否有助于减少CVD事件，这必须在专门针对Lp(a)的试验中得到证实。目前可用的药物均未被指明用于降低Lp(a)。脂蛋白分离术每次治疗可使Lp(a)水平显著降低>60%。试验数据和德国脂蛋白分离术登记处的数据表明，定期进行分离术可减少心血管事件。载脂蛋白(a)反义寡核苷酸是特异性降低Lp(a)的唯一方法。IONIS-APO(a) 1期和2期试验显示Lp(a)大幅下降且耐受性良好。肝脏特异性变体IONIS-APO(a)-L的效力高30倍。IONIS-APO(a)-L 2期试验的结果最近公布。最高剂量可使Lp(a)分别降低72%和80%；约81%和98%的患者Lp(a)水平降至<50mg/dl。耐受性和安全性得到了证实，其中注射部位反应是最常见的副作用。这让人希望计划中的3期试验将重现这些结果，并显示心血管事件减少。
