Tuomilehto J, Rastenyte D, Birkenhäger W H, Thijs L, Antikainen R, Bulpitt C J, Fletcher A E, Forette F, Goldhaber A, Palatini P, Sarti C, Fagard R
National Public Health Institute, Helsinki, Finland.
N Engl J Med. 1999 Mar 4;340(9):677-84. doi: 10.1056/NEJM199903043400902.
Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients.
After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, > or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly.
At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively).
Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients.
最近的报告表明，钙通道阻滞剂可能对糖尿病和高血压患者有害。我们之前曾报告，使用钙通道阻滞剂尼群地平进行降压治疗可降低心血管事件风险。在这项事后分析中，我们比较了尼群地平在糖尿病患者和非糖尿病患者中的治疗结果。
根据中心、性别以及既往是否存在心血管并发症进行分层后，将4695例年龄≥60岁、收缩压为160至219 mmHg且舒张压低于95 mmHg的患者随机分配接受积极治疗或安慰剂治疗。积极治疗包括尼群地平（每日10至40 mg），可能加用或换用依那普利（每日5至20 mg）或氢氯噻嗪（每日12.5至25 mg）或两者并用，通过滴定使收缩压至少降低20 mmHg并降至150 mmHg以下。在对照组中，同样给予匹配的安慰剂片。
随机分组时，492例患者（10.5%）患有糖尿病。经过两年的中位随访，糖尿病患者中，安慰剂组和积极治疗组的收缩压和舒张压分别相差8.6 mmHg和3.9 mmHg。在4203例无糖尿病的患者中，两组的收缩压和舒张压分别相差10.3 mmHg和4.5 mmHg。在对可能的混杂因素进行校正后，发现积极治疗使糖尿病患者组的总死亡率降低了55%（从每1000例患者45.1例死亡降至每1000例患者26.4例死亡），心血管疾病死亡率降低了76%，所有心血管事件合并发生率降低了69%，致命性和非致命性卒中降低了73%，所有心脏事件合并发生率降低了63%。在非糖尿病患者中，积极治疗使所有心血管事件合并发生率降低了26%，致命性和非致命性卒中降低了38%。在接受积极治疗的患者组中，糖尿病患者的总死亡率、心血管疾病死亡率和所有心血管事件的降低幅度均显著大于非糖尿病患者（P分别为0.04、0.02和0.01）。
基于尼群地平的降压治疗对老年糖尿病和单纯收缩期高血压患者特别有益。因此，我们的研究结果不支持长效钙通道阻滞剂对糖尿病患者可能有害这一假说。
