Wiysonge C S, Bradley H, Mayosi B M, Maroney R, Mbewu A, Opie L H, Volmink J
Ministry of Public Health, EPI, BP 25125 Messa, Yaoundé, Cameroon.
Cochrane Database Syst Rev. 2007 Jan 24(1):CD002003. doi: 10.1002/14651858.CD002003.pub2.
Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs.
To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension.
We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts.
We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older.
At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I(2)) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance.
Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I(2)=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I(2)=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I(2)=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I(2)=0%; ARI=0.6%, NNH=180). There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I(2)=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I(2)=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I(2)=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs.
AUTHORS' CONCLUSIONS: The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.
最近的两项系统评价发现，与其他所有抗高血压药物联合使用相比，一线β受体阻滞剂在降低中风发病率以及中风、心肌梗死和死亡的联合终点方面效果较差。然而，对于特定的结局指标，β受体阻滞剂可能比某一类特定药物更好或更差，因此将β受体阻滞剂与其他所有类别药物联合使用进行比较可能会产生误导。此外，这些系统评价并未评估β受体阻滞剂相对于其他抗高血压药物的耐受性。因此，我们进行了这项评价，以重新评估相对于其他主要类别的抗高血压药物，β受体阻滞剂作为高血压一线治疗的地位。
量化β受体阻滞剂对成年高血压患者发病和死亡终点的有效性和安全性。
我们检索了截至2006年6月的Cochrane对照试验注册库、Medline、Embase以及以往评价的参考文献列表，并联系了高血压专家，以查找符合条件的研究。
我们选择了随机对照试验，这些试验评估了β受体阻滞剂与安慰剂、无治疗或其他药物类别相比，作为高血压单一疗法或一线疗法对18岁及以上男性和非妊娠女性的死亡率和发病率终点的有效性。
至少两名作者独立应用研究入选标准、评估研究质量并提取数据；差异通过协商解决。我们将研究结果表示为相对风险（RR）及95%置信区间（CI），并对试验参与者按随机分配的组进行定量分析，无论他们实际接受了何种治疗或接受了多少治疗。在研究之间不存在显著异质性（p>0.1）的情况下，我们使用固定效应方法进行荟萃分析。否则，我们使用随机效应方法，并通过分层分析调查异质性的原因。此外，我们使用Higgins统计量（I(2)）来量化研究间效应变异性中可归因于真正异质性而非偶然性的部分。
13项符合我们纳入标准的随机对照试验（N=91561名参与者），将β受体阻滞剂与安慰剂或无治疗（4项试验，23613名参与者）、利尿剂（5项试验，18241名参与者）、钙通道阻滞剂（CCB：4项试验，44825名参与者）以及肾素-血管紧张素系统（RAS）抑制剂（3项试验，10828名参与者）进行了比较。一线β受体阻滞剂与安慰剂、利尿剂或RAS抑制剂之间的全因死亡率风险无差异，但与CCB相比，β受体阻滞剂的全因死亡率风险更高（RR 1.07，95%CI 1.00至1.14，I(2)=2.2%；ARI=0.5%，NNH=200）。与安慰剂相比，一线β受体阻滞剂的总心血管疾病（CVD）风险更低（RR 0.88，95%CI 0.79至0.97，I(2)=21.4%，ARR=0.7%，NNT=140）。这主要反映在中风显著减少（RR 0.80，95%CI 0.66至0.96；I(2)=0%；ARR=0.5%，NNT=200）；β受体阻滞剂与安慰剂之间的冠心病（CHD）风险无显著差异。β受体阻滞剂对CVD的影响显著低于CCB（RR 1.18，95%CI 1.08至1.29，I(2)=0%；ARI=1.3%，NNH=80），但与利尿剂或RAS抑制剂无显著差异。与CCB相比，总CVD增加是由于中风增加（RR 1.24，95%CI 1.11至1.40，I(2)=0%；ARI=0.6%，NNH=180）。与RAS抑制剂相比，β受体阻滞剂导致的中风也有所增加（RR 1.30，95%CI 1.11至1.53，I(2)=29.1%；ARI=1.5%，NNH=65）。β受体阻滞剂与利尿剂、CCB或RAS抑制剂之间的CHD无显著差异。此外，与使用利尿剂（RR 1.86，95%CI 1.39至2.50，I(2)=78.2%，ARI=6.4%，NNH=16）和RAS抑制剂（RR 1.41，95%CI 1.29至1.54，I(2)=12.1%；ARI=5.5%，NNH=18）的患者相比，使用β受体阻滞剂的患者因副作用而停药的可能性更大，但与CCB无显著差异。
现有证据不支持将β受体阻滞剂用作高血压治疗的一线药物。这一结论基于与安慰剂或无治疗相比，β受体阻滞剂降低中风的效果相对较弱且对冠心病无影响。更重要的是，与钙通道阻滞剂、肾素-血管紧张素系统抑制剂和噻嗪类利尿剂相比，β受体阻滞剂有导致更差结局的趋势。这些结论的大部分证据来自使用阿替洛尔作为β受体阻滞剂的试验（本评价中75%的β受体阻滞剂参与者）。然而，目前尚不清楚β受体阻滞剂对年轻和老年患者是否有不同影响，以及不同亚型的β受体阻滞剂之间是否存在差异。
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