国际循环:已经证实控制血压能降低心血管并发病率和死亡率的风险,在这一领域进行过很多临床试验。抗高血压药物的种类很多,您能在药物的选择上给我们一些建议吗?
Kjeldsen博士:这当然是一个非常重要的问题。首先,所有降低血压的不同药物都能预防心血管并发症,尤其是卒中。欧洲社会的观点是我们能够使用所有的抗高血压药物。在大多数患者中,需要进行联合用药,需要使用两种,可能三种或更多的药物来控制血压。那么关于哪一种药物最好这个问题,我认为某些患者需要联合使用多种药物才能有效控制血压。基于我们所做的试验我有一些自己的观点,在两个大型试验中,我们加入了β受体阻滞剂对主要终点进行关注,在ASCOT试验中,我们使用β受体阻滞剂作为原发性高血压的初始治疗用药。在这些试验中效果好的药物是钙通道阻滞剂,ACE抑制剂,ARBs,而这些药物大多数都结合了利尿剂共同使用的。所以我自己的观点是,我们需要结合利尿剂来使用这些抗高血压药物。
<International Circulation>: It has been firmly established that controlling blood pressure is of importance in reducing the risk of cardiovascular morbidity and mortality. There are a lot of clinic trials in this particular area and we have many different kinds of antihypertensive agents. Do you have any suggestions about the selection of these antihypertensive agents?
Professor Kjeldsen: This is of course a very important question. First of all, I mean all the different drugs that lower blood pressure also prevent against cardiovascular complications and in particular stroke. And the opinion of the European Society is that we can really use all or the entire XXX for antihypertensives. In most patients, you need combinations. You need two, or maybe three, or even more drugs to control the high blood pressure. Then the discussion about which drug is the best one. In some patients XXX you need all the drugs to control high blood pressure but in moderate hypertension I have my own opinion based on the trials we have been doing. In two large trials we have been beating the beta blockers for the primary endpoint and in a liFe study ASCOT trial we downgraded the beta blocker for primary treatment of primary hypertension. The winner in these trials were calcium antagonists, ACE inhibitors, ARBs, mostly combined with thiazide diuretics so when it comes to my personal opinion, we need to include these drugs in combination with thiazide diuretics.
《国际循环》:已经证实控制血压能降低心血管并发病率和死亡率的风险,在这一领域进行过很多临床试验。抗高血压药物的种类很多,您能在药物的选择上给我们一些建议吗?
Kjeldsen教授:这当然是一个非常重要的问题。首先,所有降低血压的不同药物都能预防心血管并发症,尤其是卒中。另外,欧洲高血压协会的观点是我们能够使用所有的医疗设备来治疗高血压。在大多数患者中,需要进行联合用药,需要使用两种,可能三种或更多的药物来控制高血压。对于那么关于哪一种药物最好这个问题,我认为某些血压较高的患者需要联合使用多种药物才能有效控制血压。对于中等程度的高血压患者基于我们所做的试验我有一些自己的观点,在两个大型试验中,我们关注了β受体阻滞剂对主要终点的影响,在ASCOT试验,我们降低了使用β受体阻滞剂作为原发性高血压的初始治疗用药。在这些试验中效果好的药物是钙通道阻滞剂,ACE抑制剂,ARBs,而这些药物大多数都结合了噻嗪类利尿剂共同使用的。所以我自己的观点是,我们需要结合利尿剂来使用这些抗高血压药物。
<International Circulation>: Stroke is extremely prevalent in China. We are a journal based in China, so it is of major concern. Is there a different in the different categories of antihypertensive drugs from the clinical trials as far as which ones perhaps is better in those specific endpoints such as stroke?
Prof. Kjeldsen: First study that really showed the difference in primary endpoints was the LIFE study. In LIFE the difference in stroke favoring the ARB versus the beta blocker was driving the difference in primary endpoint. Let us go to the ASCOT study, ASCOT was stopped a little bit prematurely because of the difference in total mortality but the largest difference in endpoint was for stroke, favoring the XXX plus ACE inhibitors plus beta blocker plus thiazide. So stroke is such an important endpoint I think the driving primary endpoint in these studies.
《国际循环》:卒中在中国非常普遍,作为来自中国的记者,当然对此尤为关注。从临床试验来讲,在不同类别的抗高血压药物中,哪一种对能减少某些特殊终点事件的发生,比如卒中的发生?
Kjeldsen教授:LIFE研究是第一个显示主要终点事件有差异的研究。在LIFE研究中,关于主要终点事件,ARB比β受体阻滞剂在预防卒中方面更好。我们来看ASCOT研究,ASCOT有点过早结束是因为总死亡率出现了明显的差异,而终点事件的最主要差异就是卒中,钙通道阻滞剂合用ACE抑制剂优于β受体阻滞剂和噻嗪类利尿剂联合使用。所以我认为卒中的发生是区分主要终点事件的重要指标。
<International Circulation>: What’s the relationship between baseline blood pressure and magnitude of blood pressure reductions during antihypertensive treatment?
Prof. Kjeldsen: Generally we tend to believe that the more we lower the blood pressure the better the outcome. There are not many possibilities of randomized studies when looking at this question. We did a hot study back in the 1990s almost 19,000 hypertensives randomized to a target below 90 to 85 to 80. The problem was that we had very small differences in blood pressure so we lost some statistical power but there was a borderline significance favoring less myocardial infarction. But if you analyze observed data, observational data from the interventional studies like the VALUE trial, in VALUE those achieved control of systolic blood pressure below 140 after six months had a much more favorable outcome compared to those who did not achieve their target within six months. We believe that the lower the better in most patients.
《国际循环》:在高血压的治疗上,基线血压和血压的降幅有什么关系呢?
Kjeldsen教授:一般来说我趋于相信血压越低结局越好。在这一问题上没有很多随机试验。我们曾经在上世纪90年代做过一个HOT研究,大约19,000名高血压患者随机分到靶血压分别为低于90,85和80的3个组中。问题在于由于血压之间的差异太小,我们失去了一些统计学的效能,但是在关于心肌梗死方面有一些临界的统计学差异。如果你分析一些干预研究的测量数据,比如VALUE研究,在这个研究中,收缩压控制在140以下的患者结局要比在6个月之内没有控制好血压的患者好得多。我们相信对大多数患者而言,血压降得越低越好。
<International Circulation>: You just mentioned “the lower the better”. Obviously we have a lot of different agents, what about the rate of the lowering. What is your point of view on that as far as an optimal time or rate or perhaps an agent – which one is a gentler action? In your view what is the ideal?
Prof. Kjeldsen: Generally we do not like to lower it within hours, maybe not within days but probably within weeks and absolutely within months. We went further and analyze the VALUE data and looked into the outcomes after one month, those with blood pressure control after one month compared to those who did not have control, there was a difference of stroke and for mortality, failing those without blood pressure control after one month. So I believe that within weeks atleast we should have blood pressure control.
《国际循环》:您刚才提到“越低越好”,很显然,我们有很多不同降压药物可供选择,降低的率又是多少呢?您对降压的最佳时期,降压率,哪一种药物降压更平缓有什么观点?您认为最理想的是什么?
Kjeldsen教授:一般来说,我们不希望在几个小时,或者几天内迅速降压,我们希望在几周或者几个月之内慢慢降压。我们对VALUE试验进行深入分析,从一个月后的结果可以看到,一个月后血压得到控制的患者与没有得到控制的患者相比,卒中的发生和死亡率都是下降的。所以我相信,至少要在数周内我们应该控制好血压。
<International Circulation>: You mention the VALUE trial, the results from the VALUE study show that there was a highly significant lower rate of new onset diabetes in the valsartan group. The LIFE study also shows Losartan reduced the rate of new onset diabetes. So, can we infer from this that ARBs are a better choice for patients with a high risk of future diabetes, for example the patient who does not currently have diabetes but he has a family history?
Prof. Kjeldsen: A patient with a family history and a high risk of metabolic syndrome and a high risk