Staessen Jan A, Wang Ji-Guang, Thijs Lutgarde
Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Departement Moleculair en Cardiovasculair Onderzoek, Katholieke Universiteit Leuven, Leuven, Belgium.
J Hypertens. 2003 Jun;21(6):1055-76. doi: 10.1097/00004872-200306000-00002.
In a meta-analysis published in October 2001, we reported that new and old classes of antihypertensive drugs had similar long-term efficacy and safety. Furthermore, we observed that in clinical trials in hypertensive or high-risk patients gradients in systolic pressure accounted for most differences in outcome.
To test whether our previous conclusions would hold, we updated our quantitative overview with new information from 14 clinical trials presented before 1 March 2003.
To compare new and old antihypertensive drugs, we computed pooled odds ratios from stratified 2 x 2 contingency tables. If Zelen's test of heterogeneity was significant, we used a random effects model. In a meta-regression analysis, we correlated odds ratios with corresponding between-group differences in systolic pressure. We then contrasted observed odds ratios with those predicted from gradients in systolic pressure.
Differences in achieved systolic blood pressure and incidence of total and cardiovascular mortality, cardiovascular events, stroke, myocardial infarction and heart failure. NEW VERSUS OLD DRUGS: In 15 trials, 120 574 hypertensive patients were randomized to old drugs (diuretics or beta-blockers) or new agents [calcium-channel blockers, alpha-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin type-1 receptor (AR1) blockers]. Old and new drugs provided similar protection against total and cardiovascular mortality and fatal plus non-fatal myocardial infarction. Calcium-channel blockers, including (-8%, P = 0.07) or excluding verapamil (-10%, P = 0.02), as well as AR1 blockers (-24%, P = 0.0002) resulted in better stroke prevention than did the old drugs, whereas the opposite trend was observed for ACE inhibitors (+10%, P = 0.03). The risk of heart failure was higher (P < 0.0001) on calcium-channel blockers (+33%) and alpha-blockers (+102%) than on conventional therapy involving diuretics. META-REGRESSION: Between-group differences in achieved systolic pressure ranged from 0.1 to 3.2 mmHg in seven actively controlled trials (73 237 patients), and from 2.1 to 22.1 mmHg in seven studies comparing varying intensities of blood pressure lowering (11 128 patients). For these 14 new trials, we predicted outcome from achieved systolic blood pressure using our previously published meta-regression models based on 30 trials with 149 407 patients. In general, predicted and observed odds ratios were similar. Larger reductions in systolic pressure (weighted mean 1.8 mmHg) in two trials accounted for the advantage of AR1 blockers over conventional therapy in the prevention of stroke. Only for cardiovascular mortality in very old patients (P = 0.02) and for cardiovascular events and myocardial infarction in old Australians (P < 0.05), the observed odds ratios deviated from our predictions based on the gradients in systolic blood pressure.
The hypothesis that new antihypertensive drugs, such as calcium-channel blockers, alpha-blockers, ACE inhibitors or AR1 blockers might influence cardiovascular prognosis over and beyond their antihypertensive effects remains unproven. The finding that blood pressure differences largely accounted for cardiovascular outcome emphasizes the desirability of tight blood pressure control. However, the level to which blood pressure must be lowered to achieve maximal benefit remains currently unknown.
在2001年10月发表的一项荟萃分析中，我们报告称新型和传统类别的抗高血压药物具有相似的长期疗效和安全性。此外，我们观察到在高血压或高危患者的临床试验中，收缩压梯度是导致结局差异的主要因素。
为了验证我们之前的结论是否仍然成立，我们利用2003年3月1日前公布的14项临床试验的新信息更新了我们的定量综述。
为了比较新型和传统抗高血压药物，我们从分层的2×2列联表中计算合并比值比。如果泽伦异质性检验显著，我们使用随机效应模型。在荟萃回归分析中，我们将比值比与收缩压的组间相应差异进行关联。然后，我们将观察到的比值比与根据收缩压梯度预测的比值比进行对比。
达到的收缩压差异以及总死亡率、心血管死亡率、心血管事件、中风、心肌梗死和心力衰竭的发生率。新型药物与传统药物比较：在15项试验中，120574例高血压患者被随机分为接受传统药物（利尿剂或β受体阻滞剂）或新型药物治疗[钙通道阻滞剂、α受体阻滞剂、血管紧张素转换酶（ACE）抑制剂或血管紧张素1型受体（AR1）阻滞剂]。新型和传统药物在预防总死亡率和心血管死亡率以及致命和非致命性心肌梗死方面提供了相似的保护。包括维拉帕米（-8%，P=0.07）或不包括维拉帕米（-10%，P=0.02）的钙通道阻滞剂以及AR1阻滞剂（-24%，P=0.0002）在预防中风方面比传统药物效果更好，而ACE抑制剂则呈现相反趋势（+10%，P=0.03）。与使用利尿剂的传统治疗相比，钙通道阻滞剂（+33%）和α受体阻滞剂（+102%）导致心力衰竭的风险更高（P<0.0001）。荟萃回归：在7项积极对照试验（73237例患者）中，组间达到的收缩压差异范围为0.1至3.2 mmHg，在7项比较不同血压降低强度的研究（11128例患者）中，差异范围为2.1至22.1 mmHg。对于这14项新试验，我们使用基于30项试验（149407例患者）的先前发表的荟萃回归模型，根据达到的收缩压预测结局。总体而言，预测的和观察到的比值比相似。两项试验中收缩压的更大降低（加权平均值1.8 mmHg）解释了AR1阻滞剂在预防中风方面优于传统治疗的优势。仅在非常老年患者的心血管死亡率方面（P=0.02）以及在老年澳大利亚人的心血管事件和心肌梗死方面（P<0.05），观察到的比值比偏离了我们基于收缩压梯度的预测。
新型抗高血压药物，如钙通道阻滞剂、α受体阻滞剂、ACE抑制剂或AR1阻滞剂，可能在其降压作用之外影响心血管预后的假设仍未得到证实。血压差异在很大程度上决定心血管结局这一发现强调了严格控制血压的必要性。然而，目前尚不清楚血压必须降至何种水平才能实现最大获益。
