Mancia G, Omboni S, Agabiti-Rosei E, Casati R, Fogari R, Leonetti G, Montemurro G, Nami R, Pessina A C, Pirrelli A, Zanchetti A
Clinica Medica, Università di Milano-Bicocca, Ospedale San Gerardo, Monza, Italy.
J Cardiovasc Pharmacol. 2000 Jun;35(6):926-31. doi: 10.1097/00005344-200006000-00015.
Recent studies showed that in diabetic hypertensive patients, administration of angiotensin-converting enzyme (ACE)-inhibitors or calcium antagonists can effectively lower blood pressure (BP) and prevent diabetes-related cardiovascular complications with no adverse metabolic effects. We sought to assess the antihypertensive and metabolic effects of the new dihydropyridine calcium antagonist manidipine (M) in patients with diabetes mellitus and essential hypertension as compared with the ACE inhibitor enalapril (E). After 3 weeks of placebo, 101 (62 men; age range, 34-72 years) hypertensives with type II diabetes mellitus were randomized to M 10-20 mg or E 10-20 mg, od, for 24 weeks. At the end of the placebo period and the active-treatment phase, BP was measured with a mercury sphygmomanometer (office, O) and over the 24 h by ambulatory (A) monitoring. ABP recordings were analyzed to obtain 24-h, day (6 a.m. to midnight), and night (midnight to 6 a.m.) average systolic (S) and diastolic (D) BP and heart rate (HR) values. Homogeneity of the antihypertensive effect over the 24 h was assessed by the smoothness index [SI: i.e., the ratio between the average of the 24 hourly BP changes after treatment and the corresponding standard deviation (the higher the SI, the more uniform is the BP control by treatment over the 24 h]. The O SBP and DBP were significantly (p < 0.01) and similarly reduced by M (16 +/- 10 and 13 +/- 6 mm Hg, n = 49) and E (15 +/- 10 and 13 +/- 6 mm Hg, n = 45). The percentage of patients whose O DBP was reduced < or = 85 mm Hg (i.e., the value indicated to be the optimal DBP goal in diabetic hypertensives) was similar for M (37%) and E (40%). The reduction of 24-h BP also was similar between M (n = 38) and E (n = 38) for both drugs (systolic, 6 +/- 11 and 8 +/- 10 mm Hg; diastolic, 5 +/- 8 and 5 +/- 7; NS, M vs. E). The antihypertensive effect was distributed in a similar homogeneous fashion throughout the dosing interval, as shown by the similar SI values (M, 0.6 +/- 1.2 for SBP and 0.6 +/- 0.9 for DBP; E, 0.6 +/- 0.8 for SBP and 0.5 +/- 0.7 for DBP; NS, M vs. E). O and A HR were unchanged by either treatment. Markers of glucose and lipid metabolism and renal function were not significantly modified by treatment both with M and with E. In the diabetic hypertensives, M was as effective and metabolically neutral as the ACE-inhibitor E.
近期研究表明，在糖尿病高血压患者中，给予血管紧张素转换酶（ACE）抑制剂或钙拮抗剂可有效降低血压（BP），并预防糖尿病相关的心血管并发症，且无不良代谢影响。我们试图评估新型二氢吡啶类钙拮抗剂马尼地平（M）与ACE抑制剂依那普利（E）相比，对糖尿病合并原发性高血压患者的降压及代谢作用。在3周的安慰剂期后，101例（62例男性；年龄范围34 - 72岁）II型糖尿病高血压患者被随机分为马尼地平10 - 20 mg组或依那普利10 - 20 mg组，每日一次，治疗24周。在安慰剂期结束和积极治疗阶段结束时，使用汞柱式血压计测量诊室血压（O），并通过动态血压监测（A）测量24小时血压。分析动态血压记录以获取24小时、日间（上午6点至午夜）和夜间（午夜至上午6点）的平均收缩压（S）、舒张压（D）和心率（HR）值。通过平滑指数评估24小时降压效果的均匀性[平滑指数：即治疗后24小时每小时血压变化平均值与相应标准差的比值（平滑指数越高，治疗在24小时内对血压的控制越均匀）]。马尼地平（16±10和13±6 mmHg，n = 49）和依那普利（15±10和13±6 mmHg，n = 45）显著降低（p < 0.01）且相似程度降低诊室收缩压和舒张压。诊室舒张压降低至≤85 mmHg（即糖尿病高血压患者的最佳舒张压目标值）的患者百分比，马尼地平组（37%）和依那普利组（40%）相似。两种药物在马尼地平组（n = 38）和依那普利组（n = 38）中24小时血压降低情况也相似（收缩压，6±11和8±10 mmHg；舒张压，5±8和5±7；马尼地平与依那普利比较，无显著性差异）。如相似的平滑指数值所示（马尼地平，收缩压为0.6±1.2，舒张压为0.6±0.9；依那普利，收缩压为0.6±0.8，舒张压为0.5±0.7；马尼地平与依那普利比较，无显著性差异），降压效果在整个给药间隔内以相似的均匀方式分布。两种治疗均未改变诊室和动态心率。马尼地平和依那普利治疗均未显著改变血糖和脂质代谢及肾功能指标。在糖尿病高血压患者中，马尼地平与ACE抑制剂依那普利降压效果相同且对代谢无不良影响。
