Dunbar Richard L, Goel Harsh
Department of Medicine, Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, 9-010 Maloney Building, Philadelphia, PA, 19104, USA.
Curr Atheroscler Rep. 2016 Feb;18(2):11. doi: 10.1007/s11883-016-0563-8.
Niacin was the first drug demonstrating lowered cholesterol prevents coronary heart disease (CHD) events, with two clinical CHD outcome studies establishing a cardioprotective niacin regimen: 1 g thrice daily with meals. Though cardioprotective, skin toxicity limits niacin's use, fostering several variations to improve tolerability. One of these, an extended-release (ER) alternative, proved immensely successful commercially, dominating clinical practice despite departing from the established regimen in several critical ways. Hence, improved tolerability may have come at the cost of diminished efficacy, posing a conundrum: Does it still help the population at risk for CHD to broaden a drug's acceptance by "watering it down"? This question is crucial at this stage now that the ER alternative failed to recapitulate the benefits of the established cardioprotective niacin regimen in two trials of the alternative approach: AIM-HIGH and HPS2-THRIVE. Part I of this review discusses how vastly the ER alternative departs from the established cardioprotective regimen, why that is important physiologically, and how it may explain the findings of AIM-HIGH and HPS2-THRIVE. Given important gaps left by statin therapy, the established cardioprotective niacin regimen remains an important evidence-based therapy for the statin intolerant or statin averse.
烟酸是第一种被证明降低胆固醇可预防冠心病（CHD）事件的药物，两项临床CHD结局研究确立了一种具有心脏保护作用的烟酸治疗方案：每日三次，每次1克，与餐同服。尽管具有心脏保护作用，但皮肤毒性限制了烟酸的使用，促使人们进行了多种改进以提高耐受性。其中一种改进型，即缓释（ER）制剂，在商业上取得了巨大成功，尽管在几个关键方面与既定方案有所不同，但仍主导着临床实践。因此，耐受性的提高可能是以疗效降低为代价的，这就带来了一个难题：通过“稀释”药物来扩大其接受度，对冠心病高危人群是否仍有帮助？鉴于在两项采用替代方法的试验（AIM-HIGH和HPS2-THRIVE）中，ER制剂未能重现既定的具有心脏保护作用的烟酸治疗方案的益处，这个问题在现阶段至关重要。本综述的第一部分讨论了ER制剂与既定的心脏保护方案有多大差异，这种差异在生理上为何重要，以及它如何解释AIM-HIGH和HPS2-THRIVE的研究结果。鉴于他汀类药物治疗存在重要差距，既定的具有心脏保护作用的烟酸治疗方案对于不耐受或厌恶他汀类药物的患者仍然是一种重要的循证治疗方法。
