International Circulation: Also previous studies have demonstrated that only when a statin significantly lowers LDLc levels and raises HDLc levels, can substantial atherosclerotic regression be obtained. What do you think is the appropriate way to choose statin agents when a physician is aiming to reduce coronary atherosclerosis to prevent future CV events? IC:既往有研究提示,只有当他汀治疗显著降低LDL-C并同时升高HDL-C水平时,才能实现斑块逆转。为逆转斑块从而预防未来心血管事件,您认为医生在处方他汀时应如何选择? Dr Harrington: Here is where we rely on the guidelines. There are guidelines both in the US and in other areas of the world where the clinical trials for primary prevention and secondary prevention have been well analyzed and well considered. In those guidelines, they offer us as practitioners, goals for LDL reduction. Looking at the area that I work most closely in, which is acute ischemic heart disease, in the guidelines for patients with acute ischemic heart disease, the professional organizations recommend we lower LDLc less than 100 and they give us an optional guideline based on that particular patient’s risk, lower than 70. Then one can look at the different statins and try to understand the relative potency so if you have a patient starting with a particular level of LDL, you ought to be able to predict what level of LDL you can get that patient to utilizing different doses of statins. I think if people keep their target in mind and choose their statin on the basis of being able to achieve that target, our patients will be well-served. Dr Harrington: 遵循指南还是我们首先要强调的。美国和全球各地区指南都对一级预防和二级预防临床试验做了很好的分析和总结。指南对LDL-C治疗目标值做出了明确要求。例如我本人主要治疗的急性缺血性心脏病患者,指南建议将急性缺血性心脏病患者的LDL-C目标值降至<100 mg/dl,最佳目标值为<70 mg/dl。基于此我们应了解不同他汀的降脂强度,根据患者的基线LDL-C水平确定其治疗目标,以此选择不同剂量的他汀。牢记该患者的治疗目标并据此选择能够实现该目标的他汀药物,患者就能得到很好的治疗。 International Circulation: The safety issue is always the important issue especially involving the drug interactions of statins. With regard to the safety issue, what are your thoughts on statins? IC:安全性尤其是他汀与其他药物间相互作用引起的安全性问题非常重要。您如何评价他汀治疗的安全性? Dr Harrington: The best way to choose a statin is to look at the potency of LDL you are trying to achieve and secondly to look at statins that have associated large safety data bases. That typically comes from large randomized trials with many thousands, if not tens of thousands, of patients where we can look at the side effects. The side effects being largely muscle-related side effects and sometimes liver and we should monitor these sorts of things when we see our patients and talk to our patients and recognize that a reaction and adverse reaction to one statin does not exclude you from trying another statin for example. Part of that becomes the art of medicine coupled with an understanding of the science of medicine. We have a lot yet to learn. We realize that there are patients who obviously have different genetic make-ups that may affect the metabolism of some of these drugs; different genetic make-ups that may affect the metabolism of multiple drugs that perhaps use competing pathways for their metabolism. We are still in an era where we are sorting that out. My prediction is that we will get to a point where looking at a patient’s characteristics which includes their genetic characteristics, will allow the physician to most appropriately choose drugs from which the patient can get good benefit while minimizing the risk. We still have to work towards that. There will be sessions at this meeting to address some of these issues. In the US, this has been referred to as personalized medicine; trying to understand the best drug, the best dose and the best side effect profile for an individual. This is a field in which a lot of work remains to be done. Dr Harrington: 选择他汀药物最重要的是依据其降低LDL-C以实现治疗达标的能力,其次是基于其相关的大规模安全性数据。这种数据多来源于纳入数千甚至上万例患者的、可充分观察不良反应的大型试验。他汀不良反应多为肌肉或肝脏相关的事件,我们必须严密监测并充分告知患者,需要认识到,一种剂量的他汀如果出现不良反应并不意外着不能尝试另一种他汀。我们知道部分患者具有不同基因型从而影响某些药物的代谢,如果某种基因型影响多种药物代谢,则可能造成药物间竞争代谢途径。我预计将来我们可以根据患者特征,包括其基因特征,来选择对其获益最大而风险最低的最为适宜的药物。
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