<International Circulation>: The polypill is a hot topic at this meeting. What are the most important advantages of using a polypill instead of a multiple drug strategy?

　　Dr. Prabhakaran: The polypill as a strategy has several advantages although there are people who say it has disadvantages also. The main advantage is that it is a single drug; the patient is not taking three or four drugs at the same time. The second advantage is that it can bring down the cost if generic drugs are used in the combination. The third advantage is that it takes into account the multiple risks that are involved and as a consequence， the absolute risk so that people take the drug based on absolute risk and there are no further investigations required. This is the hypothesis that was put forward by Wald and Law about ten years ago. But there are issues with the polypill. For example， a smoker may have a very high risk. Do we ask the smoker to take a polypill or ask him to stop smoking? If a person is obese， do we give them a polypill to help them to reduce risk or ask them to exercise or other strategies to lose weight? Those are fundamental philosophical issues with polypills. But in terms of secondary prevention， for example， the polypill has brought a huge amount of pluses.

　　《国际循环》：多效片是本次大会的亮点之一。与多药联合治疗相比，多效片最重要的优势体现在哪些方面？

　　Prabhakaran博士：作为一种治疗策略，多效片有优点也有缺点。主要优势是多效片是一片药，患者不需要同时服用3、4种。其次，如果与仿制药联用，费用会更低。第三，多效片考虑了多种风险以及可能导致的后果，患者服药的绝对风险可预计。但是多效片也有争议，例如，吸烟者应服用多效片还是戒烟？肥胖患者应当服用多效片还是多运动减重？这是多效片的哲学问题，但在二级预防方面，多效片还是能带来很多获益。

　　<International Circulation>: How do you balance the need for individualizing therapy and the convenience of using one pill for all?

　　Dr. Prabhakaran: The reason for individualizing therapy is that some of us believe that each patient is different and each patient’s requirements are different and that is why we would want to individualize therapy. The fact of the matter is， after a heart attack， for example， there is the need for four simple drugs: a statin， a beta-blocker， aspirin and an ACE-inhibitor. The reality is that in most countries including China， nearly 60% of people are not getting any treatment one year after the event. To simplify this， the polypill will be a great mechanism. While it is important to individualize with initial therapy， a polypill is excellent as secondary prevention. In primary prevention， of course， we need more evidence from trials to see if there is benefit in terms of reduction of blood pressure and lipid profiles. I’m sure studies will show that but it needs to translate into hard clinical outcomes.

　　《国际循环》：如何平衡个体化治疗的需求以及所有患者服用单药的便利度？

　　Prabhakaran博士：患者病情各异，所以每位患者的需求不同，这也是个体化治疗的原因。如心脏病发作后，患者需要服用4种药：他汀、β受体阻滞剂、阿司匹林和血管紧张素转换酶抑制剂（ACEI）。但事实上，大部分国家包括中国在内，近60%患者在发病后一年内未接受任何治疗，多效片能让这类患者的治疗更简便。尽管初始治疗的个体化很重要，但多效片在二级预防中的作用可圈可点。一级预防中我们需要更多临床试验证据观察多效片是否对降低血压和血脂有益。试验肯定会显示出获益，但转化成临床疗效还需观察。

　　<International Circulation>: Would there be a worry about overusing medication in primary prevention where a polypill targets several different mechanisms?

　　Dr. Prabhakaran: That’s a real danger. However， take hypertension， for example. Hypertension doesn’t occur alone. A person with hypertension has diabetes， has high lipid levels and so on， so a polypill could be made with half-dose drugs which can have fewer side effects but can actually counter many of these factors. In that respect， a polypill might be useful. The issue here is what types of polypills will be required in primary prevention? What is the dosage that may be required for individual drug components? What kinds of drugs will be required because there are multiple drugs effective against blood pressure， multiple drugs effective against lipids and multiple drugs for diabetes? What is the right combination? This is one of the areas we need to work on.

　　《国际循环》：由于多效片可作用于多个靶点，如果在一级预防中过度应用是否引人担忧？

　　Prabhakaran博士：过度用药很危险，但也不尽然。以高血压为例，高血压并不独立发生。高血压患者通常伴糖尿病、高血脂等合并症，多效片通常由半数剂量的多种药物制成，因此不良反应较少又能控制危险因素。在这方面，多效片的效果值得肯定。问题是一级预防中需要哪种多效片？个体化用药的剂量多大才合适？由于降压药、调脂药和降糖药都有很多种，哪一种药物是必须的？如何搭配最佳？这是领域内需要继续研究的问题。

　　<International Circulation>: Cardiologists might be worried about undertreatment of patients using a polypill who might need a higher dose of certain drugs.

　　Dr. Prabhakaran: I wouldn’t worry too much about undertreatment because even where you start off with a polypill， there is the option to increase doses or adding-on drugs. You might say that defeats the purpose of giving a single drug. There could be two doses of a polypill – one high dose and one low dose. After starting on the low dose pill， a patient can step up to the high dose if the need arises.

　　《国际循环》：心血管医生是否会担心如果多效片治疗不足的患者未来需要更大剂量药物治疗？

　　Prabhakaran博士：治疗不足的问题无需担心，从用多效片治疗开始，患者就可以选择增加剂量或增加药物种类，这也许违背了单药治疗的初衷。多效片的剂量也分为大剂量和小剂量，开始用小剂量治疗后，如果病情需要，患者可以逐步增加至大剂量。

　　<International Circulation>: Do you think it’s a good idea to produce a range of polypills with different doses and different drug combinations?

　　Dr. Prabhakaran: I think there is a need for polypills for multiple diseases. A hypertension polypill. A diabetes polypill. A coronary artery disease polypill. A stroke polypill. And a heart failure polypill. Secondly， there would be a requirement for at least two doses of a polypill， maybe more. The polypill would also be an evolving thing. Drugs go off patent， better drugs become available， so there would be a shift in the drugs used in polypills. We need to keep abreast of the changes that are happening in medicine.

　　《国际循环》：您是否认为有必要将多效片设置成不同剂量和不同成分组合？

　　Prabhakaran博士：为多种疾病制造多效片是有必要的，如高血压多效片、糖尿病多效片、冠状动脉病多效片、卒中多效片、心衰多效片等。其次，多效片可能需要至少两种剂量或更多。多效片也是逐步进化的药品，当药品过了专利保护期，会有更好的药物用于临床，所以多效片的应用也需紧跟医学前进的步伐。

　　<International Circulation>: What about adding metformin into a polypill?

　　Dr. Prabhakaran: Adding metformin to a polypill is a great idea actually， especially for patients with prediabetes with other risk factors or even patients with diabetes. The biggest problem with metformin is that it is a large drug. It is somewhat difficult to add it to a polypill. The current technology does not make the pill smaller， so until that technology comes along， it is going to be difficult.

　　《国际循环》：在多效片中加入二甲双胍如何？

　　Prabhakaran博士：在多效片中加入二甲双胍是不错的理念，特别是对合并其他危险因素的前期糖尿病患者或已确诊的糖尿病患者。最大的问题是二甲双胍体积太大，某种程度上很难加入多效片的组分。现阶段研究并不能将药片缩小，除非有新技术，否则依然比较困难。

　　<International Circulation>: In randomized controlled trials concerning polypills versus usual care， control care is much better than the usual care， so how do you address this question of assessing the polypill against usual care?

　　Dr. Prabhakaran: This is an interesting and difficult issue to manage because， as a strategy， you have to compare usual care to the polypill.  We did a trial for the UMPIRE trial in India and parts of Europe (the Netherlands， Ireland and the UK) with different health systems. In the UK， for example， free medications apply to the polypill group and the usual care group so they equalized each other out a bit， but even then there was an improved adherence of around 30%. Taking the polypill had such advantages in taking a single pill that people keep using it. But it is very difficult to do a controlled trial with polypills unless we have multiple placebos for polypills it is going to be very difficult. So we need to do pragmatic open trials that take care of all of the precautions that are required to address all the biases that may occur in trials.

　　《国际循环》：随机对照试验关注多效片和常规治疗的疗效，控制治疗优于常规治疗，在对比多效片和常规治疗疗效的问题上您怎么看？

　　Prabhakaran博士：这个现象很有趣，但也很难管理，因为作为治疗策略来说，不得不将多效片和常规治疗作比较。我们曾在印度和欧洲不同医疗系统下进行UMPIRE研究，在英国多效片和常规治疗疗效相当，但多效片的依从性比常规治疗高30%，这是多效片和单药相比的优势，患者能持续用药。但对多效片做对照试验很困难，除非设置多种成分的安慰剂多效片治疗组。所以需要进行实用性开放研究，对试验中所有可能发生的偏差采取预防措施。

　　<International Circulation>: Even with those adversities， if you don’t get a positive result from trials， could you still promote the use of polypills?

　　Dr. Prabhakaran: For secondary prevention， it is a no-brainer. Even if there is no difference， I would recommend the polypill because it is much easier for the patient to take and there may be a cost advantage to it.

　　《国际循环》：如果试验无法得到阳性结果，是否继续推广多效片的使用？

　　Prabhakaran博士：对二级预防而言这是个简单的问题。即使试验结果没有显著差异，多效片依然值得推荐，因为患者服药更简便，经济上更划算。