International Circulation: The ASCOT-LLA trial demonstrated the significant benefits of adding atorvastatin to hypertension treatment in adults with three or more risk factors for heart disease. For the hypertensive patient with three or more risk factors for heart disease or hypertension with target organ damage without CVD what is the most appropriate time to start statin therapy? What would be the greatest benefit of this statin therapy?
《国际循环》：根据ASCOT-LLA试验结果，证实高血压治疗基础上加用阿伐他汀，能够使有3种以上心脏病危险因素的患者明显获益。高血压合并三个或以上危险因素，高血压合并靶器官损害，尚未发生CVD，在什么时候起动他汀治疗最合适？以及联合他汀主要带来的获益是什么？

Professor Shephard: It’s clear that when you discover a patient who has a cardiovascular risk factor problem， the sooner you get that patient onto therapy， the better. There’s no point in waiting until the patient develops a particular profile of risk， or a particular blood pressure， or particular cholesterol level before you start treatment. If they have a total global risk of an event that you think is actionable， you should get them started on treatment right away and that treatment does not necessarily have to target only the risk factor that seems to be the one that is causing the problem， but any management strategy that will lower global risk， whether it be lowering blood pressure or lowering cholesterol， will actually benefit that patient. So， you can have a patient who is hypertensive， perhaps whose hypertension is resistant to intervention， who would benefit from added statin as well. So I recommend that you consider global management strategies that include all of the risk factors and intervention against all of the risk factors that you can reasonably approach.

Shephard教授: 对于有心血管危险因素的患者，他汀治疗越早越好，无需等到患者出现特征表现，或血压、胆固醇升至某个特定值。如果你认为他们有发病的危险，应立即让他们开始接受治疗，并且该治疗不仅仅针对导致该疾病的可能因素，任何能够降低发病危险的治疗措施，或降低血压或降低胆固醇，对患者都是有利的。所以，对单纯降压治疗疗效不佳的高血压患者，增加他汀治疗也可能起效。我认为理想的治疗措施是应考虑所有危险因素并对这些危险因素进行干预的综合治疗措施。

International Circulation: Currently， hypertension control is less than satisfactory in much of the population and patient compliance is an important cause of this less than satisfactory control of blood pressure. When we consider the management of multiple risk factors for hypertensive patients， how can we effectively improve patient compliance? Does a polypill have more benefits?

《国际循环》：目前高血压控制并不理想，患者的依从性差是血压达不到有效控制的一个重要原因，在强调对高血压患者采取全面管理多重心血管危险因素的趋势下，如何有效提高患者的依从性？单片复方制剂是否具有更多的优势，请谈谈您的看法？

Professor Shephard: One of the difficulties of treating patients who have risk of cardiovascular disease is that you can treat multiple risk factors all at one time. That means， in general terms， giving multiple drugs. If you give multiple drugs to a patient， the rate at which that patient will drop out of therapy rises with the increment and number of drugs used. If you could package these drugs into a single pill， you would save the problem of that patient requiring to compartment his day in order to take half a dozen pills over the course of the 16 hours that he is awake. Polypills are a great idea in theory. There is a practical difficulty with polypills， and that is that sometimes it’s very difficult to actually produce a pill that contains multiple drugs， which may interact with each other in an adverse way. So， a polypill with 6 elements in it， which was suggested sometime back， is probably a million miles away， but pills with 2 components are on the market right now and are effective and will minimize the patients’ problems in terms of compliance.

Shephard教授:有心血管危险患者治疗的难点之一是需要同时处理多个危险因素。通常情况下这意味着患者需要同时服用多种药物，如果你给患者服用多种药物，患者退出治疗的风险会随着你使用药物的数量增加而增加。如果你将这些药物制成一粒药，患者就不必在他醒着的12或16小时内为服用半打药片而忙碌一天。多疗效药片是一个很好的治疗方法。但制作多疗效药片有实际困难，有时候很难真的制成一片药能够包含多种药物，有可能相互作用会产生不良反应。所以，一片包含6种元素的药片距离实现还有很长的路，但含有2种成分的药片在市面上已经有售并且有效，它将会最大程度减少患者依从性问题。

International Circulation: Do you feel the new data coming out for atorvastatin and amlodipine is encouraging that this combination in a polypill will be helpful?
《国际循环》：您是否认为阿伐他汀和氨氯地平的联合药片应用对患者有帮助？

Professor Shephard: The atorvastatin and amlodipine combination is a particular case in point. There you are dealing with two of the major elements of cardiovascular risk and you are dealing with them by combining effectively these two treatment strategies which makes it a lot easier for the patient to comply. I think that kind of combination where you are looking at the major elements of risk is the one that drug companies should tackling， and amlodipine and atorvastatin is clearly a good combination.

Shephard教授：阿伐他汀和氨氯地平的联合应用确实是一个特例。在处理心血管危险的两个主要因素时，将两种治疗措施有效结合，使患者更加容易服从。我认为这种将主要危险因素结合的药物是制药公司应该研发的，阿伐他汀和氨氯地平无疑是一个好的结合。

International Circulation: The main result of the ASCOT-LLA trial was that atorvastatin reduced the relative risk of the primary endpoint of non-fatal myocardial infarction and fatal CHD events by 36% (p<0.0001) in hypertensive patients with additional risk factors and without CHD. However， atorvastatin reduced the relative risk of the primary endpoint by 53% (p<0.0001) in the amlodipine group， whereas the risk of this outcome was reduced non-significantly， by just 16%， among those on atenolol. What do you think of these results? What could be the possible mechanism of the difference between the amodipine group and the atenolol group?

《国际循环》： ASCOT-LLA的结果证实高血压伴有其他心血管危险因素的患者中，阿托伐他汀可将主要终点事件（非致死性心肌梗死和致死性冠心病）的相对危险度降低36％（P<0.0001）。而进一步的2×2研究证明，氨氯地平为基础的降压方案加用阿托伐他汀主要终点事件降低达到53%，而阿替洛尔为基础的降压方案加用阿托伐他汀主要终点仅降低16%，无显著性差异。您是怎样看待这一试验结果的？能否分析一下差异发生的可能机制？

Professor Shephard: When you are looking at the outcome of a clinical trial， you should not deal in terms of relative risk reduction or relative risk change because you have no idea how that relates to clinical practice. What you should be looking at is the absolute benefit that any one individual sees. What you need to do is translate your numbers of relative risk reduction into absolute benefit and then you will see quite clearly that absolute benefit in those who are getting the aggressive intervention with the combination therapy is much better. That means that you can go with confidence to your patient and give that combination.
Shephard教授：当你看到临床试验结果时，你不应该分析相对风险的降低或变化，因为你不知道它怎样跟临床实践相结合。你应该看的是绝对利益。你需要做的是将相对风险转换成绝对利益，你会清楚看到侵入性介入加上联合治疗的绝对利益更好。这表示你可以给患者信心，给予联合治疗。

International Circulation: Thank you for taking the time to speak to us today professor.

版面编辑：张家程

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shepherd阿伐他汀氨氯地平他汀ASCOT-LLA试验