对于高血压患者而言，24小时平稳的血压和心率控制非常重要。研究发现，在高血压患者心血管事件的预测方面，与日间血压相比，夜间和清晨血压可能是更好的预测因素；心率是高血压患者的重要独立危险因素之一，而夜间心率比日间心率能更好地预测心血管事件。服药最后4小时的血压和心率可真实反映出长效降压药是否可以达到真正的24小时覆盖。

比索洛尔和美托洛尔缓释片（SR）是目前广泛应用的两种长效β受体阻滞剂，二者均可每天口服1次。比索洛尔的长效性归因于其较长的血浆半衰期；而美托洛尔SR的长效性主要源自于其持续释放的剂型。目前尚不清楚这两种药物的长效性是否存在差异。由中南大学湘雅医院杨天伦教授牵头的“比较富马酸比索洛尔和美托洛尔缓释片对轻中度高血压患者的血压和心率控制（CREATIVE）”的研究结果于米兰当地时间2015年6月13日在本届ESH年会上展示，研究旨在比较比索洛尔与美托洛尔SR的长效性，具体观察两种药物治疗12周后，对服药最后4小时的平均动态心率和血压的控制情况。

该研究为2011年12月~2014年4月开展的一项随机、多中心、平行、开放标签的临床研究，共从中国7家医院纳入186例轻中度高血压（WHO分级的Ⅰ级和Ⅱ级）门诊患者。研究主要疗效终点为治疗12周最后4小时的平均动态舒张压（DBP）和平均动态心率的改变；次要疗效终点为最后4小时的平均动态收缩压（SBP）改变，平均24小时动态SBP和DBP的改变，平均日间和夜间的动态SBP和DBP的改变，平均24小时动态心率改变，平均日间和夜间动态心率、血压和心率应答率的改变；其他终点包括药物安全性和依从性。

结果发现，降低最后4小时平均动态心率方面，比索洛尔比美托洛尔SR更有效；在降低最后4小时平均动态DBP方面，比索洛尔非劣效于美托洛尔SR。在降低平均24小时、日间和夜间动态心率方面，比索洛尔优于美托洛尔SR。亚组分析发现，基线临床心率>80次/分的患者中，比索洛尔显示出更有效地控制平均动态心率作用。另外，比索洛尔的药物依从性稍好。两组的总体不良事件及药物相关不良事件发生率相似，研究期间均未发现两种药物有新的安全问题。

专题报道>>>2015欧洲高血压学会科学年会（ESH2015）

摘要：SUPERIOR DYNAMIC HEART RATE CONTROL AND NON-INFERIOR BLOOD PRESSURE CONTROL WITH BISOPROLOL VS METOPROLOL SUSTAINED RELEASE TABLET IN MILD-TO-MODERATE HYPERTENSION: CREATIVE STUDY（PP.LB01.01）

Objective: Both bisoprolol and metoprolol sustained release tablet (SR) are indicated in the management of hypertension. While long duration of effect in metoprolol SR was achieved through its sustained-release formulation, bisoprolol has intrinsic long duration of action. This study aimed to investigate long action of bisoprolol compared with metoprolol SR in controlling mean dynamic heart rate and diastolic blood pressure in the last 4 hours of a 12-week treatment period in patients with mild-to-moderate primary hypertension

Design and method: 186 mild-to-moderate hypertensive patients from 7 centers in China were enrolled in this randomized, parallel, multicenter, open-label clinical study from Dec 2011 to Dec 2014. Patients were treated with either bispoprolol 5–10 mg or metoprolol SR 47.5–95 mg once daily for 12 weeks. Primary end points were mean dynamic heart rate control and mean dynamic diastolic blood pressure control in the last 4 hours of the treatment period. Secondary endpoints included ambulatory monitoring of the blood pressure and heart rate, safety, and compliance.

Results: A total of 186 subjects were enrolled and analyzed, 93 subjects in each group respectively. In the last 4 hours of the treatment period, bisoprolol demonstrated significantly better control of mean dynamic heart rate compared with metoprolol SR (LSmeans difference: –3.79 bpm,97.5% CI: –7.45, –0.14)).

In the last 4 hours of the treatment period, the LSmeans difference of diastolic blood pressure was –1.00 (97.5% CI: –4.79, 2.78), with the upper limit less than 4, indicating that bisoprolol group was noninferior to metoprolol sustained release tablets group bisoprolol further provided significantly better control in 24 hour mean ambulatory, mean daytime, and nighttime heart rate. The overall adverse event (AE) rate was similar in bisoprolol group and metoprolol SR group (20.43% vs 17.20%). Noncompliance was reported in 3(3.53%) and 6(7.32%) subjects in bisoprolol and metoprolol sustained release tablets group respectively.

Conclusions: Both bisoprolol and metoprolol SR could have long action. Bisoprolol provided superior dynamic heart rate control and non-inferior dynamic blood pressure control vs metoprolol SR in patients with mild-to-moderate hypertension.No new safety concern was found.

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