根据BEAUTIFUL研究结果，Procoralan*（Ivabradine）是第一个能够减少稳定性冠心病患者心肌梗死（心脏病发作）和血运重建术的抗心绞痛药物。
2008年8月31日，德国慕尼黑.倍受期待的BEAUTIFUL研究(评价If通道抑制剂Ivabradine对冠心病伴左心功能不全患者发病率/死亡率的作用)结果显示，伴有左心功能不全（LVD）且心率70次/分钟以上的冠心病（CVD）患者，心血管死亡及发生其他心血管事件的风险显著增高，在这些患者中（心率大于70次/分钟以上者），即使他们已经接受了现有的最佳治疗方案，采用Ivabradine进行治疗仍能将最重要的冠脉事件，如致死性和非致死性心肌梗死及冠状动脉重建术的风险进一步降低三分之一。BEAUTIFUL研究执行委员会主席Kim Fox教授在结果公布后的评论中指出：“一直以来Ivabradine都被认为能够减轻心肌缺血。BEAUTIFUL研究结果显示，Ivabradine是第一个能够减少心肌梗死和血运重建术的抗心绞痛药物，且与其他药物联合使用具有良好的耐受性。这是评价任何抗心绞痛和抗心肌缺血药物的金标准。”
BEAUTIFUL研究于2004年12月启动，是在独立执行委员会的指导下进行的。第一例患者入组时间是2005年早期，共有10917例合并LVD的CAD患者入组，这些患者来自4个大洲33个国家的781个研究中心。患者的平均心率是71次/分钟，其中一半患者的心率在70次/分钟以上。BEAUTIFUL研究结果显示，心率≥70次/分钟的患者有更大的可能性发生死亡或其他心血管事件。这些患者心血管死亡风险增加34％，心肌梗死、心力衰竭和冠状动脉重建术的风险分别增加46％、56％与38％。
在纳入研究的整个患者群体中，Ivabradine并未能使主要复合终点（心血管死亡、因急性心肌梗死的入院率和因心力衰竭的入院率）显著降低。但对于基线心率大于70次/分钟的患者，Ivabradine能够将因致死性和非致死性心肌梗死而住院的风险显著降低36%（P=0.001），同时将冠状动脉重建术的风险降低30%（P=0.016）。值得注意的是，这些患者中的大多数已经在接受心血管疾病治疗指南所推荐的治疗，包括抗血小板药物（94%），血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂(91%)，β受体阻滞剂（87%）以及降脂药物（76%）。由于BEAUTIFUL研究首次证实，即使对那些正在接受当前最佳心血管疾病治疗方案的患者，采用Ivabradine治疗，同样可以在单纯降低心率的基础上进一步降低冠脉事件的风险。因此，BEAUTIFUL研究结果对这些心率在70次/分钟以上冠心病患者的治疗是一个突破。该研究也证实了Ivabradine的安全性和良好的耐受性。Ivabradine能够与所有心血管疾病的常规处方药物联合应用。指导委员会主席Roberto Ferrari教授在对该研究结果进行评论时指出：“冠心病患者经常接受诸多指标的检测，却未进行简单的心率测量。BEAUTIFUL研究强化了对所有CAD患者进行心率测量的必要性，同时强调对于心率大于70次/分钟的CAD患者，需要在原治疗基础上加用Ivabradine以降低患者的心率。”
Ivabradine能够减轻慢性稳定性心绞痛患者的心肌缺血，这可以解释为什么在BEAUTIFUL研究中Ivabradine能降低不良终点事件的发生率1。新的研究已证实Ivabradine能够改善内皮细胞的功能障碍2和防止动脉粥样硬化的进展。
尽管冠心病的治疗已取得许多的进展，但据世界卫生组织报告，直到2030年，冠心病仍将是世界范围内最主要的医疗保健难题
3。
然而，BEAUTIFUL的研究结果提示人们Ivabradine将有助于改善这一局面，因为BEAUTIFUL研究显示Ivabradine能够降低心肌梗死和血运重建术的风险。BEAUTIFUL研究执行委员会主席Kim Fox教授在最后总结时说：“一半的冠心病患者在静息时心率超过70次/分钟，这些患者现在能够从Ivabradine的治疗中获益，该药物将极大降低他们再次出现心脏病发作或者需要进一步手术治疗的几率”。
参考文献：
1. Tardif J-C， Ford I， Tendera M， et al. Eur Heart J. 2005;26:2529-2536.
2. Florian Custodis， MD*; Magnus Baumhäkel， et al Circulation 2008;117:2377-2387.
3. Projections of Global Mortality and Burden of Disease from 2002 to 2030 PLoS Med 3(11): e442. doi:10.1371/journal.pmed.0030442.
英文原文：
With the BEAUTIFUL results， Procoralan* (ivabradine) is the first antianginal treatment shown to reduce myocardial infarction (heart attack) and revascularisation in stable coronary patients
Munich， Germany， 31 August， 2008. The results of the much awaited BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with CAD and left ventricULar dysfunction) trial have shown that coronary artery disease (CAD) patients with left ventricular dysfunction (LVD) and a heart rate more than 70 bpm have a significantly higher risk of cardiovascular death and other cardiovascular events and in these patients (heart rate above 70 bpm) treatment with ivabradine further reduces the risk of the most important coronary events such as fatal and non-fatal myocardial infarction and coronary revascularisation by one third， even when these patients are already receiving optimal therapy. Commenting after the results presentation， the Chairman of the BEAUTIFUL Executive Committee， Prof Kim Fox said ‘Ivabradine was always known to relieve ischemia. With the BEAUTIFUL results， ivabradine is the first antianginal treatment shown to reduce myocardial infarction and revascularisation and to have a good tolerability profile even when used with other drugs. This is the gold standard for any antianginal， anti-ischemic drug’.
The BEAUTIFUL trial was initiated in December 2004， under the guidance of an independent Executive Committee with the first patient being enrolled in early 2005. 10917 CAD patients with LVD， were recruited in 781 centres in 33 countries across 4 continents. The mean heart rate in these patients was 71 bpm and half of the patients had a heart rate more than 70 bpm. The results of the BEAUTIFUL study have shown that these patients with heart rate > 70 bpm are more likely to die or suffer from another cardiovascular event. The increase in risk is 34% for cardiovascular death， 46% for myocardial infarction， 56% for heart failure and 38% for coronary revascularisation.
In the overall study population treatment with ivabradine did not result in a significant reduction of the primary composite end point (Cardiovascular death， admission to hospital for acute MI and admission to hospital for heart failure). However in patients with baseline heart rate more than 70 bpm， ivabradine significantly reduced the risk of hospitalisation for fatal and non-fatal myocardial infarction by 36% (p=0.001) and the risk of coronary revascularisation by 30% (p=0.016). What is important to note is that most of these patients were already receiving the guidelines-recommended cardiovascular therapy: antiplatelet agents (94%)， angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (91%)， β-blockers (87%)， as well as lipid-lowering agents (76%). Hence the results of BEAUTIFUL constitute a step further in the management of these coronary patients with heart rate above 70 bpm because， for the first time it has been shown that pure heart rate reduction with ivabradine further reduces coronary events even in patients receiving the current optimal cardiovascular therapy. This study also confirms that ivabradine is safe and well tolerated and can be used with all routinely prescribed cardiovascular drugs. Commenting on the results the Chairman of the Steering Committee， Prof Roberto Ferrari said ‘Often a lot of investigations are performed in coronary patients but a simple heart rate measurement is not done. BEAUTIFUL has reinforced the need to measure heart rate in all CAD patients and if the heart rate is more than 70 bpm to reduce it by using ivabradine on top of background therapy.’
BEAUTIFUL results with ivabradine can be explained by its well documented ability to relieve myocardial ischemia in patients with chronic stable angina.1 New research has demonstrated that ivabradine improves endothelial dysfunction2 and prevents the progression of atherosclerosis.
Despite all the advances， the World Health Organisation reports that till 2030 coronary artery disease will remain the leading healthcare problem worldwide3. Ivabradine would help to reduce this burden because as shown by the BEAUTIFU