1. <International Circulation>: More than 30，000 patients at high risk of CV complication from 41 countries are recruited for the study of ONTARGET， involving 1，700 Chinese patients. As the Asia-Pacific Regional Coordinator of the study， could you please talk about the evolvement of ONTARGET in China and why are Chinese patients selected to the study?

《国际循环》：ONTARGET研究在41个国家纳入了三万多名心血管高危患者，其中在中国也有1700名患者参与了该研究，您作为亚太地区的协调者，请您谈谈中国ONTARGET研究的开展情况以及为什么会考虑入选中国的患者？

Prof. Peter Sleight: I think there are two very clear results from the ONTARGET study. And as you say it’s of great interest because it’s the first study like this which includes a lot of people from Asia and we are very grateful for China for joining in the goals， not only in this trial but in many of the trials we are doing， we have a fantastic collaboration with the Chinese physicians. And the data quality is extremely good and the recruitment is very good. So I am very pleased to have you in it. The important messages are that we have shown in this population as I suppose to say a heart failure or post-MI population. We have shown it in elderly high risk population that telmisartan is absolute equivalent to ramipril the ACEI. And it’s better tolerated and there is much less cough， much less angioneurotic edema and both of these are important. And I think possibly for the Chinese population the cough is a very important thing because my understanding is that the cough is more common with ACEI in China. That’s what I have been told with much experience. So that’s very important. The safety of the two are absolutely equal. 

The second important result was that it was unexpected to us was that when we combined the two which in many small trials are shown to have some benefits， there was no overall benefit in this trial. So not only was there was no overall benefit， there was some harm. And the harm was from excessive renal failure and excessive hypotension and syncope. So those are two very important messages. I think if you are going to use this combination of ARB and ACEI， you’ll have to be absolutely obsessional about monitoring patients. You have to pick your patients， maybe some heart failure patients， the combination is good. But in this population without heart failure， largely people with hypertension and vascular disease， it’s not a good combination. I think you need to lower BP by combination of different classes of drugs. Don’t try to block the renin-angiotensin system too hard. Because if you do， the patients get into some intercurrenting illness， the dehydrates， diarrhea， this could be dangerous， this could be tipping them into renal failure. When if you just have one of the agents， there is some leeway， some possibility to escape.  

Peter Sleight教授：我认为，ONTARGET研究有两个非常显著的结果。正如你所提到的，ONTARGET研究具有很重要的意义。ONTARGET研究是纳入大样本亚洲患者的首个研究，我们非常感谢中国能够参与该研究，中国不仅参加了ONTARGET研究，还参加了其他多项研究。与中国的医生的合作非常愉快，数据质量相当不错，病例入组也很好。因此，我非常高兴你们能参与本研究。我们发现的重要结果是，在这些老年高危患者中（心衰和心肌梗死患者），特米沙坦与ACEI类药物雷米普利的疗效相近。但是特米沙坦的耐受性更好，咳嗽更为少见，血管神经性水肿明显减少。咳嗽和血管神经性水肿都很重要。我认为，对于中国患者来说咳嗽是非常重要的，因为我了解到中国患者服用ACEI时咳嗽更为常见。特米沙坦和雷米普利的安全性相似。

第二个重要结果就是，当将两种药物联合分析时，该试验不但没有总体益处，还有害处，来自肾衰、血压过低和晕厥发生率的增加。这是我们没有预料到的。这两种药物以往已经在多个小样本的临床试验中被证实有效。因此，这就是该试验的两个非常重要的结果。我认为，如果你想联用ARB和ACEI，必须要注意严密监测患者。严格选择病例，联合治疗可能对某些心衰患者有利。但是，对于不合并心衰的患者，主要是高血压和血管性疾病的患者，ARB加ACEI并不是好的联合治疗方案。我认为，需要通过联合不同种类的药物来降低血压。不要过分阻断RAS。因为如果这样做的话，患者会合并某些疾病，例如脱水或腹泻，可能对患者有危险，导致肾衰。如果只用一种RAS阻断药物的话，还有回旋的余地。

2. <International Circulation>: Activated RAAS palys a major role in the onset of insulin resistance and atherosclearosis， to blockade RAAS can interrupt the chain of the progress of cardiovascular events， from atherosclearosis to myocardial infarction， storke， blood vessel remodlling and eventually to death.Underpressure is the basis strategy of reducing the risk of CV， according to the result of ONTARGET， would you please talk about the benefits being independent of the BP-lowering effect through blocking RAS system?

《国际循环》：肾素血管紧张素醛固酮系统(RAAS)激活在高血压伴胰岛素抵抗和动脉粥样硬化的发病中起主导作用，阻断RAAS可打断心血管事件链的每个环节，从动脉粥样硬化到心梗、卒中再到血管重塑直至死亡。降压是降低心血管危险的最基本的策略，结合ONTARGET研究结果，请您谈谈阻断RAAS系统带来了哪些降压以外的益处？

Prof Peter Sleight：I think the blockade of the RAS in the hypertension， post MI， DM and many high risk people is absolutely a problem. And this just gives us two equal alternatives for treatment. There is no doubt for stroke， the lower the BP， the better. But for the other， MI， for cardiovascular death， for heart failure， it’s not such good evidence that you have to go too low with BP. 

Peter Sleight教授：我认为，在高血压、心肌梗死、糖尿病和多个高风险人群中，阻断RAS系统绝对是个需要考虑的问题。ONTARGET研究为我们提供了两个选择。毫无疑问，对于卒中患者来说血压越低越好。但是对于心肌梗死、心血管死亡、心衰患者，则没有很好的证据支持需要将血压降的很低

3. <International Circulation>: As the Principal Investigator and Study Chair， you have said “the ONTARGET™ Trial Programme patient population is more representative of what we typically see in everyday clinical practice. Importantly， the trial reflects the changing approach to cardiovascular disease prevention – looking not at managing specific diseases such as diabetes or hypertension， but at managing individual patients with complex combinations of risk factors.” How can we understand?

《国际循环》：ONTARGET研究对象都是临床实践中常见的患者群，您作为该研究的首席研究员和主席曾指出该研究非常重要的一点是改变了心血管疾病的预防途径，即不是简单的仅仅针对特殊疾病如糖尿病和高血压的管理，而是对合并有多种危险因素的患者的个体化管理。您能否对此做一个较详细的解读？

Prof Peter Sleight：I think it’s important that you try to reduce blood pressure risk in people who are at high risk and you try to do it by many methods. And one is to use statins. Antoher is to lower the BP， the third is to block the RAS. The fourth is antiplatelet agents. So you use a mix of these things. 

Peter Sleight教授：我认为，重要的是应当尝试降低高危人群的高血压风险，这可以通过下述几种方式做到，包括他汀类药物治疗、降低血压、阻断RAS和应用抗血小板制剂。因此，需要上述药物的联合应用。