Drugs for dyslipidaemia: the legacy effect of the Scandinavian Simvastatin Survival Study (4S)

Timo E Strandberg, Petri T Kovanen, Donald M Lloyd-Jones, Frederick J Raal, Raul D Santos, Gerald F Watts
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Abstract

Since the discovery of statins and the Scandinavian Simvastatin Survival Study (4S) results three decades ago, remarkable advances have been made in the treatment of dyslipidaemia, a major risk factor for atherosclerotic cardiovascular disease. Safe and effective statins remain the cornerstone of therapeutic approach for this indication, including for children with genetic dyslipidaemia, and are one of the most widely prescribed drugs in the world. However, despite the affordability of generic statins, they remain underutilised worldwide. The use of ezetimibe to further decrease plasma LDL cholesterol and the targeting of other atherogenic lipoproteins, such as triglyceride-rich lipoproteins and lipoprotein(a), are likely to be required to further reduce atherosclerotic cardiovascular disease events. Drugs directed at these lipoproteins, including gene silencing and editing methods that durably suppress the production of proteins, such as PCSK9 and ANGPTL3, open novel therapeutic options to further reduce the development of atherosclerotic cardiovascular disease.
治疗血脂异常的药物:斯堪的纳维亚辛伐他汀生存研究(4S)的遗产效应
自从三十年前发现他汀类药物和斯堪的纳维亚辛伐他汀生存研究(4S)结果以来,血脂异常(动脉粥样硬化性心血管疾病的主要危险因素)的治疗取得了显著进展。安全有效的他汀类药物仍然是这一适应症(包括遗传性血脂异常儿童)治疗方法的基石,也是世界上处方量最大的药物之一。然而,尽管非专利他汀类药物价格低廉,但在全球范围内仍未得到充分利用。要进一步减少动脉粥样硬化性心血管疾病的发生,可能需要使用依折麦布来进一步降低血浆低密度脂蛋白胆固醇,并针对其他致动脉粥样硬化脂蛋白,如富含甘油三酯的脂蛋白和脂蛋白(a)。针对这些脂蛋白的药物,包括持久抑制 PCSK9 和 ANGPTL3 等蛋白生成的基因沉默和编辑方法,为进一步减少动脉粥样硬化性心血管疾病的发生提供了新的治疗选择。
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