Division of Cardiology, Department of Medicine, The Johns Hopkins Ciccarone Preventive Cardiology Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Cardiol Rev. 2011 Jan-Feb;19(1):17-22. doi: 10.1097/CRD.0b013e3181fc212a.
Statins have been shown to reduce cardiovascular events. However, despite widespread use of statin therapy, residual cardiovascular risk remains, and this has left clinicians searching for an effective adjunctive therapy to optimize lipid profiles and reduce risk further. Given the cost and duration of large event driven trials, adjunctive lipid lowering therapy options have largely been evaluated through surrogate measures of atherosclerosis, making clinical practice decisions regarding combination therapy difficult. Two common approaches that have been evaluated almost entirely by surrogate outcome trials include the addition of ezetimibe or the addition of niacin. Our article attempts to place these surrogate end point trials in their proper context, providing clinicians with a practical approach to making clinical practice decisions regarding adjunctive therapy in the absence of clinical outcomes data. Although definitive changes to lipid lowering guidelines should be based on clinical outcomes trials, in the absence of clinical outcomes data, it is reasonable to make individualized clinical practice decisions on the basis of surrogate measures of disease as long as there is corroboration among the effect on atherosclerosis and lipid parameters as adjunctive therapy, and clinical outcomes as monotherapy. Given that niacin fits these criteria, it seems prudent to support the use of niacin as adjunctive therapy in combination with maximally tolerated dose of statin in patients with low high-density lipoprotein-cholesterol and known coronary artery disease. Three ongoing clinical outcomes trials evaluating niacin and ezetimibe in combination with statin will provide more definitive word regarding the safety and efficacy of these agents as adjunctive therapy.
他汀类药物已被证明可降低心血管事件风险。然而，尽管广泛使用他汀类药物治疗，仍然存在残留的心血管风险，这使得临床医生在寻找有效的辅助治疗方法来优化血脂谱并进一步降低风险。鉴于大型事件驱动试验的成本和持续时间，辅助降脂治疗选择主要通过动脉粥样硬化的替代指标进行评估，这使得关于联合治疗的临床实践决策变得困难。已经通过替代终点试验评估了两种常见的方法，包括添加依折麦布或添加烟酸。我们的文章试图将这些替代终点试验置于适当的背景下，为临床医生在缺乏临床结果数据的情况下提供关于辅助治疗的临床实践决策的实用方法。尽管降低血脂指南的明确改变应基于临床结果试验，但在缺乏临床结果数据的情况下，根据疾病的替代指标做出个体化的临床实践决策是合理的，只要在作为辅助治疗时，对动脉粥样硬化和血脂参数的影响以及单药治疗时的临床结果之间存在一致性。鉴于烟酸符合这些标准，因此似乎明智的是，在患有低高密度脂蛋白胆固醇和已知冠心病的患者中，支持将烟酸与最大耐受剂量的他汀类药物联合用作辅助治疗。目前正在进行三项评估烟酸和依折麦布与他汀类药物联合使用的临床结果试验，将提供关于这些药物作为辅助治疗的安全性和有效性的更明确信息。
