Masana Luis, Civeira Fernando
Unitat de Medicina Vascular i Metabolisme, Hospital Universitari Sant Joan, Universitat Rovira i Virgili, IISPV, CIBERDEM, Reus, Tarragona, España.
Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Servicio de Medicina Interna, Hospital Universitario Miguel Servet, IIS Aragón, Red de Investigación Cardiovascular (RIC), Zaragoza, España.
Clin Investig Arterioscler. 2016 May;28 Suppl 2:22-30. doi: 10.1016/S0214-9168(16)30167-X.
The achievement of low-density lipoprotein (LDL) therapeutic targets is especially difficult in some patients at high cardiovascular risk. These patients include persons with statin intolerance and those with very high LDL cholesterol (LDLc) levels such as persons with familial hypercholesterolemia. The proportion of statin-intolerant patients is between 7% and 29%. Alternative lipid-lowering drugs (including ezetimibe) are less effective and are not free from adverse effects. Both alirocumab, with the ODYSSEY ALTERNATIVE study, and evolocumab, with the GAUSS study, have shown strong lipid-lowering efficacy, with much greater tolerability than currently available alternatives, with the result that a larger number of patients achieve therapeutic targets. In familial hypercholesterolemia, the monogenic metabolic disease most frequently associated with high cardiovascular risk, early intervention is cost-effective. Although statins have substantially improved the prognosis of familial hypercholesterolemia, many affected individuals are far from achieving the recommended therapeutic targets. In this patient group, PCSK9 inhibition with monoclonal antibodies has also been shown to be highly effective in reducing LDLc, especially in heterozygous individuals. The studies performed to date have shown that these drugs are safe and effective and can help many patients with familial hypercholesterolemia to drastically reduce their cardiovascular risk.
在一些心血管风险较高的患者中，实现低密度脂蛋白（LDL）治疗目标尤其困难。这些患者包括他汀类药物不耐受者以及LDL胆固醇（LDLc）水平非常高的患者，如家族性高胆固醇血症患者。他汀类药物不耐受患者的比例在7%至29%之间。其他降脂药物（包括依折麦布）效果较差且并非没有不良反应。在ODYSSEY ALTERNATIVE研究中的阿利西尤单抗以及在GAUSS研究中的依洛尤单抗均显示出强大的降脂功效，耐受性比现有替代药物好得多，结果是更多患者实现了治疗目标。在家族性高胆固醇血症（最常与高心血管风险相关的单基因代谢疾病）中，早期干预具有成本效益。尽管他汀类药物已显著改善了家族性高胆固醇血症的预后，但许多受影响个体远未达到推荐的治疗目标。在该患者群体中，使用单克隆抗体抑制前蛋白转化酶枯草溶菌素9（PCSK9）在降低LDLc方面也已显示出高效，尤其是在杂合子个体中。迄今为止进行的研究表明，这些药物安全有效，可帮助许多家族性高胆固醇血症患者大幅降低心血管风险。
