β受体阻滞剂在降压治疗中失去光芒

美国科罗拉多州斯诺马斯——如今，β受体阻滞剂或许已经失去了几十年来作为高血压一线治疗的地位。

在斯诺马斯召开的美国心血管年会上，来自纽约西奈山医学院的医学教授Clive Rosendorff博士称：“总的来看，我认为现已形成共识，即对于没有并发症的高血压患者，β受体阻滞剂并不是一个好的选择。”


Clive Rosendorff博士
 
Rosendorff博士指出，充足的证据表明，β受体阻滞剂预防卒中和心肌梗死(MI)以及降低总死亡率的效果不及其他类型的降压药物。而且，其肾脏保护作用不及雷米普利，逆转左室肥厚的效果也不及其他降压药物。

此外，正如传输动脉功能评估(CAFE)研究所示，β受体阻滞剂存在所谓的“假降压疗效”：即中心动脉压的下降程度达不到收缩压的下降程度，这可能解释了为何其心脏保护作用不及其他降压药物。而且，β受体阻滞剂还与胰岛素抵抗增加、运动耐力下降、体重增加以及副作用导致的高停药率相关。

Rosendorff博士是美国心脏病学会(ACC)/美国心脏协会(AHA)/美国高血压学会(ASH)联合委员会的主席，该委员会负责起草了即将公布的关于缺血性心脏病预防与管理中的高血压治疗的修订版科学声明。他也是2007年AHA关于该主题科学声明的起草委员会主席(Circulation 2007;115:2761-88)。

对于β受体阻滞剂作为无并发症高血压一线用药的缺点，自2007年AHA科学声明发布以来最具说服力的证据之一是对6项meta分析进行的meta分析。这6项meta分析总共纳入了26项比较β受体阻滞剂与安慰剂的随机试验。其结论是：β受体阻滞剂虽然使卒中风险相对下降16%~22%，但在预防MI和死亡方面并没有优于安慰剂(J. Am. Coll. Cardiol. 2007;50:563-72)。

这项meta-meta分析还纳入了3项比较β受体阻滞剂与利尿剂对照试验的meta分析以及3项比较β受体阻滞剂与其他药物的meta分析。结果显示，从MI、卒中和死亡率这三个终点来看，β受体阻滞剂显著劣于其他抗高血压药物。

需要注意的是，这些临床试验和meta分析几乎全部局限于阿替洛尔和短效美托洛尔。

作为心脏病专家，Rosendorff博士指出：“对于新一代β受体阻滞剂，我们还没有类似的数据。对于卡维地洛，尚未从高血压结局的角度对其进行过评价。比索洛尔和奈必洛尔也是一样。当我们找到数据支持这些新一代β受体阻滞剂用于降压治疗时，这种模式有可能会发生相当大的转变。”

Rosendorff博士表示，尚不能就即将公布的ACC/AHA/ASH科学声明中提出的推荐意见发表评价。他强调其关于β受体阻滞剂不适用于无并发症的高血压的评论仅代表其个人观点，而不一定是整个专家小组的观点。

不过，值得一提的是，在最近公布的第八届全国联合委员会(JNC 8)报告中推荐了四类可以作为高血压初始治疗的抗高血压药物，其中并没有β受体阻滞剂(JAMA 2014;311:507-20)。

Rosendorff博士声明无相关经济利益冲突。

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By: BRUCE JANCIN, Cardiology News Digital Network

SNOWMASS, COLO. – Beta-blockers have lost their decades-long status as first-line therapy for hypertension.

"Generally, I think there is a consensus that beta-blockers are a poor choice for uncomplicated hypertension," Dr. Clive Rosendorff observed at the Annual Cardiovascular Conference at Snowmass.
 
Abundant evidence indicates that beta-blockers provide less protection against stroke, MI, and overall mortality than other classes of antihypertensive agents. They offer less renal protection than ramipril and achieve less regression of left ventricular hypertrophy than other antihypertensive drugs.

Moreover, as was shown in the Conduit Artery Function Evaluation (CAFE) study, beta-blockers have what has been termed "pseudo-antihypertensive efficacy": that is, they fail to reduce central aortic blood pressure to the same extent they lower systolic blood pressure, which may explain why they are less cardioprotective than other antihypertensive drugs. They also are associated with an increase in insulin resistance, reduced exercise tolerance, weight gain, and a high rate of withdrawal because of side effects, said Dr. Rosendorff, professor of medicine at Mount Sinai School of Medicine, New York.

Dr. Rosdendorff chaired the joint American College of Cardiology/American Heart Association/American Society for Hypertension committee that wrote the soon-to-be-released revised scientific statement on the treatment of hypertension in the prevention and management of ischemic heart disease. He also chaired the 2007 AHA scientific statement on the subject (Circulation 2007;115:2761-88).

One of the most persuasive pieces of evidence of the shortcomings of beta-blockers as first-line agents for uncomplicated hypertension to appear since the release of the 2007 AHA scientific statement was a meta-analysis of six meta-analyses. The six meta-analyses incorporated a total of 26 randomized trials of beta-blockers versus placebo. The conclusion: beta-blockers were no better than placebo in preventing MI or mortality, although they did result in a 16%-22% relative reduction in stroke risk (J. Am. Coll. Cardiol. 2007;50:563-72).

This meta-meta-analysis also included three meta-analyses of comparative trials of beta-blockers versus diuretics and three meta-analyses of beta-blockers compared with other drugs. Beta-blockers turned out to be significantly worse than the other antihypertensive agents in terms of the three endpoints of MI, stroke, and mortality.

A caveat: these clinical trials and meta-analyses were nearly all restricted to atenolol and short-acting metoprolol.

"We don’t have any comparable data for newer beta-blockers. Carvedilol has never been looked at from the point of view of outcomes in hypertension. Bisoprolol likewise, and nabivolol, too. It’s possible that the paradigm might be changed quite considerably when we have data to support the use of these newer beta-blockers in the treatment of hypertension," the cardiologist said.

Dr. Rosendorff noted that he wasn’t at liberty to discuss the recommendations of the forthcoming ACC/AHA/ASH scientific statement in advance of its release. He stressed that his comments on the drawbacks of beta-blockers for uncomplicated hypertension represented his own views and not necessarily the panel’s.

Of note, however, is that the recently published report of the Eighth Joint National Committee (JNC 8) doesn’t list beta-blockers among the four classes of antihypertensive medications recommended for the initial treatment of hypertension (JAMA 2014;311:507-20).

Dr. Rosendorff reported having no financial conflicts of interest.