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The future direction of cholesterol-lowering therapy.

机译：降胆固醇治疗的未来方向。

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PURPOSE OF REVIEW Observational studies suggest a continuous positive relationship between vascular risk and cholesterol without any lower threshold level. We review recent and future clinical trials addressing the question of optimal treatment goals for cholesterol reduction and how these relate to present guidelines. With increasing focus on greater cholesterol reduction, new approaches to lipid-lowering therapy are being developed; we discuss some of these agents including the new statin, rosuvastatin and novel cholesterol transport inhibitors such as ezetimibe.RECENT FINDINGS The Heart Protection Study demonstrated that LDL cholesterol reduction to levels as low as 1.7 mmol/l was associated with significant clinical benefit in a wide range of high-risk individuals, irrespective of baseline cholesterol levels, with no apparent threshold level for LDL cholesterol with respect to cardiovascular risk. The Heart Protection Study also demonstrated that the benefits of LDL cholesterol reduction extend into peripheral vascular disease and cerebrovascular disease prevention and suggest that the most recent National Cholesterol Education Program Adult Treatment Panel III guidelines, with LDL cholesterol targets of 2.6 mmol/l, may result in undertreatment of a large number of patients. Various large end-point trials, including Treating to New Targets and Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine will attempt to further address the issue of optimal LDL cholesterol reduction. New therapies are being developed to meet the challenge of more intensive cholesterol lowering. Rosuvastatin is a potent, hydrophilic enantiomeric statin producing reductions in LDL cholesterol of 40-69% over its dose range of 5-80 mg. Ezetimibe is a selective cholesterol absorption inhibitor, with a site of action at the intestinal epithelium. Optimum reductions in LDL cholesterol of up to 25 and 60% reduction in chylomicron cholesterol content are seen with a 10-mg dose.SUMMARY Evidence is accumulating supporting the safety and benefits of aggressive cholesterol reduction, with no apparent threshold for LDL cholesterol. New therapies will aid in achieving lower cholesterol levels and the use of combination therapies targeting different aspects of cholesterol metabolism may produce additional benefits. Outcome studies are awaited to further address these issues.
机译：审查的目的观察性研究表明，血管风险和胆固醇之间存在持续的正相关关系，而没有任何较低的阈值水平。我们回顾了有关降低胆固醇的最佳治疗目标以及它们与当前指南的关系的最新和未来临床试验。随着人们对降低胆固醇的日益关注，正在开发新的降脂治疗方法。我们讨论了其中的某些药物，包括新的他汀类药物，瑞舒伐他汀和新型胆固醇转运抑制剂，例如依泽替米贝。最新发现心脏保护研究表明，低密度脂蛋白胆固醇降低至1.7 mmol / l的水平与广泛的临床获益相关。与基线胆固醇水平无关的高危人群，对于心血管风险，LDL胆固醇没有明显的阈值水平。心脏保护研究还表明，降低LDL胆固醇的益处可扩展到周围血管疾病和脑血管疾病的预防，并建议可能导致最新的国家胆固醇教育计划成人治疗小组III指南，其LDL胆固醇目标为2.6 mmol / l。大量患者的治疗不足。各种大型终点试验，包括“治疗新靶点”和“胆固醇和同型半胱氨酸的进一步降低效果的研究”，将尝试进一步解决最佳降低LDL胆固醇的问题。正在开发新的疗法来应对进一步降低胆固醇的挑战。罗苏伐他汀是一种有效的亲水性对映体他汀类药物，在其5-80毫克剂量范围内可使LDL胆固醇降低40-69％。依泽替米贝是一种选择性的胆固醇吸收抑制剂，在肠道上皮具有作用部位。剂量为10 mg时，LDL胆固醇的最佳减少量最多为25，乳糜微粒胆固醇的含量减少60％。总结不断积累的证据支持积极降低胆固醇的安全性和益处，没有明显的LDL胆固醇阈值。新疗法将有助于降低胆固醇水平，针对胆固醇代谢不同方面的联合疗法可能会产生更多益处。等待结果研究以进一步解决这些问题。

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