<International Circulation>: You have just participated in a very active and lively debate about maximizing beta-blockers and adding Ivabradine in heart failure patients with high heart rate. Would you please briefly review this topic and summarize the benefits and shortcomings of beta-blockers and Ivabradine, respectively? What do you believe are the residual questions that remain?
《国际循环》:您刚参加了一场非常活跃和热烈的关于在高心率的心力衰竭患者中将β受体阻滞剂用至最大量并加用伊伐布雷定的辩论。您能否简要回顾这一主题,并概括一下β受体阻滞剂和伊伐布雷定分别有什么优缺点?您认为还有哪些未能解答的问题?
Prof.Swedberg: We have studied patients who remain at an elevated heart rate, which is known to be an increased risk. We could also show in our SHIFT study that patients with a heart rate above 70 have an incremental risk, which exponentially increases with higher and higher heart rates. A clinician should be concerned and should reduce the heart rate. What we did was to require that the patients were on recommended therapy, including a beta-blocker, initiated according to the ESC guidelines. We very carefully documented if they were not on such therapy. Upon analysis we found that 56% were only on at least 50% of the recommended background dose. That has been criticized because it begs the question why weren’t these patients on a higher dose of beta-blockers? They should have been on 100% of the recommended doses. We know however that that is impossible. So the problem is what is the dose level they would ask for. When we look into other contemporary trials or registries we see that today you cannot up-titrate patients to the levels requested when the trials were designed, sometimes more than 50 years ago. That was just picking doses randomly and forcing patients into these trials. Today it is different, patients are different, and they have different background treatments with much more ACE inhibitor treatments, higher dose levels, etc. We think that we managed to have an optimized background therapy and on top of that we lowered heart rate with Ivabradine, whose exclusive cardiovascular effect is lowering heart rate. There have been no reported constituent effects such as lowering blood pressure, no psychological side-effects, so it is very well tolerated. Then we sorted out the data an saw that cardiovascular outcomes were reduced significantly. Today I also presented that the patients reported an overall improvement in how they felt. That improvement in health related quality of life is actually related to the magnitude of the heart rate reduction. This last finding has absolutely not been shown with beta-blockers where, at best, a patient doesn’t deteriorate in terms of quality of life. That is a major difference.
Prof.Swedberg:我们已经研究了心率仍然较高的患者,众所周知这些患者的风险升高。我们还在我们的SHIFT研究中证明,心率大于70的患者有增量风险,且这一风险随着心率越来越高而成指数升高。临床医生应该予以关注,且应当降低心率。我们所做的是要求患者接受推荐的治疗,包括根据ESC指南着手的β受体阻滞剂。如果他们没有接受这种治疗,则我们会非常仔细地记录。经分析我们发现,仅56%的患者在接受所推荐背景剂量的至少50%。这一直在被批判,因为它引出了一个问题,即为什么这些患者未在接受更高剂量的β受体阻滞剂?他们本来应该接受推荐剂量的100%。 然而,我们知道那是不可能的。因此,问题是他们要求的剂量水平是什么。当我们研究其他当代试验或注册研究,我们看到,今天你不能将患者向上滴定至试验设计时(有时是超过50年前)所要求的水平。那仅仅是随机挑选的剂量并强迫患者进入这些试验。今天一切都不同了,患者是不同的,且他们有着不同的背景治疗,如更多的ACE抑制剂治疗,更高的剂量水平等。我们认为,我们设法优化背景治疗,并在此基础上,我们用伊伐布雷定来降低心率,其独有的心血管作用就是降低心率。尚无报告有组成作用如降压,无心理上的不良反应,因此其耐受性非常好。然后,我们整理出这些数据,看到心血管终点被显著降低。今天,我还展示了患者报告他们感觉上的全面改善。实际上,健康相关生活质量上的这一改善与心率降低的幅度有关。而β受体阻滞剂绝对尚未证明这一最新结果,充其量,患者在生活质量方面不恶化。这是一个重大的区别。