Poulter Neil R, Wedel Hans, Dahlöf Björn, Sever Peter S, Beevers D Gareth, Caulfield Mark, Kjeldsen Sverre E, Kristinsson Arni, McInnes Gordon T, Mehlsen Jesper, Nieminen Markku, O'Brien Eoin, Ostergren Jan, Pocock Stuart
Imperial College London, London, UK.
Lancet. 2005;366(9489):907-13. doi: 10.1016/S0140-6736(05)67186-3.
Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0.86 and 0.77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation.
We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates.
We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0.86 (0.77-0.96) to 0.88 (0.79-0.98) and from 0.77 (0.66-0.89) to 0.83 (0.72-0.96), respectively. Multivariate adjustment gave HRs of 0.94 (0.81-1.08) for coronary events (HDL cholesterol being the largest contributor) and 0.87 (0.73-1.05) for stroke events.
Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.
盎格鲁-斯堪的纳维亚心脏结局试验-降压组（ASCOT-BPLA）的结果显示，与接受以阿替洛尔为基础的联合药物治疗方案的个体相比，接受以氨氯地平为基础的联合药物治疗方案的个体发生冠状动脉事件和中风事件的发生率显著更低（风险比分别为0.86和0.77）。我们的目的是评估这些差异在多大程度上归因于随机分组后血压及其他变量的显著差异。
我们使用了ASCOT-BPLA的数据（n = 19257），并比较了试验中连续时间点累积平均血压水平的差异与冠状动脉和中风事件的连续差异。采用收缩压差异的序列均值匹配来调整这些事件差异的风险比。我们使用更新的Cox回归模型来评估各种血压测量值、血清高密度脂蛋白胆固醇、甘油三酯和钾、空腹血糖、心率及体重的累积平均水平差异对事件发生率差异的影响。
我们未发现血压差异大小与不同事件发生率之间存在时间关联。收缩压差异的序列均值匹配使冠状动脉和中风事件的风险比降低的程度，与Cox回归分析中收缩压差异调整的程度相似。经血压调整后的冠状动脉事件和中风事件的风险比分别从0.86（0.77 - 0.96）升至0.88（0.79 - 0.98），以及从0.77（0.66 - 0.89）升至0.83（0.72 - 0.96）。多变量调整后，冠状动脉事件的风险比为0.94（0.81 - 1.08）（高密度脂蛋白胆固醇是最大的影响因素），中风事件的风险比为0.87（0.73 - 1.05）。
多变量调整解释了ASCOT-BPLA中所测试的治疗方案之间冠状动脉事件差异的约一半以及中风事件差异的约40%，但残留差异不再显著。这些残留差异可能表明统计调整不足，但两种治疗方案对其他变量的不同影响也有可能导致了所观察到的不同发生率，尤其是中风。
