Radevski I, Skudicky D, Candy G, Sathekge S, Strugo V, Sareli P
Department of Cardiology, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.
Am J Hypertens. 1999 Feb;12(2 Pt 1):194-203. doi: 10.1016/s0895-7061(98)00233-7.
A single-center, prospective double-blind randomized trial was conducted to compare the efficacy and safety of the calcium channel blocker nisoldipine in a sustained release coat-core formulation (CC), titrated from 10 mg to 40 mg daily, with the angiotensin converting enzyme inhibitor enalapril, titrated from 10 to 40 mg daily, in the treatment of black South African patients with severe hypertension (sitting diastolic blood pressure [DBP] between 115 and 140 mm Hg, confirmed by 24-h ambulatory blood pressure monitoring). Treatment target was a sitting DBP < 95 mm Hg by the 9th week of treatment. This was followed by a 4-month open phase using nisoldipine CC 10 to 60 mg daily. Ninety-six patients had complete data at baseline, and at the end of the double-blind and open phases, and were included in this analysis. In both groups, all patients required titration up to the maximal dose of double-blind medication. Monotherapy with nisoldipine CC, but not enalapril, significantly reduced both sitting and 24-h ambulatory blood pressure (BP). Twenty-four-hour BP in the nisoldipine CC group decreased from 179+/-14 / 118+/-7 to 144+/-16 / 94+/-10 mm Hg (P < .0001) versus 181+/-13 / 117+/-5 to 171+/-17 / 110+/-11 mm Hg in the enalapril group (P = ns). The profound decrease in blood pressure achieved with nisoldipine CC was accompanied by a significant reduction in left ventricular [LV] mass index, observed after only 2 months of treatment (from 146+/-40 to 129+/-35 g/m2, P = .05). In contrast, enalapril had no effect on LV mass (from 139+/-36 to 142+/-50 g/m2, P = NS). The antihypertensive effect of nisoldipine CC was further demonstrated in the open phase, during which 24-h BP decreased from 180+/-14 / 118+/-6 mm Hg (at baseline) to 142+/-16 / 92+/-10 mm Hg at the end of the 16-week open phase (P < .0001). This effect was sustained with trough-to-peak ratio of 74% for systolic and 67% for diastolic BP, with further regression in LV mass. Reduction in 24-h systolic BP to < 135 mm Hg was associated with a greater degree of regression of LV mass index in patients treated with nisoldipine CC. The incidence of adverse events in both groups was low and both nisoldipine CC and enalapril were well tolerated. The incidence of significant ventricular arrhythmia was also low and did not change with treatment. In conclusion, our findings suggest that nisoldipine CC administered once daily could be considered as a suitable first-line antihypertensive agent in black patients with severe hypertension, based on its profound and sustained blood-pressure-lowering effect, associated with significant regression of left ventricular mass and its low side effect profile.
进行了一项单中心、前瞻性双盲随机试验，以比较钙通道阻滞剂缓释包衣片硝苯地平控释片（CC）（每日剂量从10毫克滴定至40毫克）与血管紧张素转换酶抑制剂依那普利（每日剂量从10毫克滴定至40毫克）治疗南非黑人重度高血压患者（经24小时动态血压监测确认，坐位舒张压[DBP]在115至140毫米汞柱之间）的疗效和安全性。治疗目标是在治疗第9周时坐位DBP<95毫米汞柱。随后是为期4个月的开放期，使用每日10至60毫克的硝苯地平控释片。96例患者在基线、双盲期和开放期结束时均有完整数据，并纳入本分析。两组患者均需要滴定至双盲药物的最大剂量。硝苯地平控释片单药治疗可显著降低坐位和24小时动态血压（BP），而依那普利则不能。硝苯地平控释片组24小时血压从179±14/118±7毫米汞柱降至144±16/94±10毫米汞柱（P<.0001），而依那普利组从181±13/117±5毫米汞柱降至171±17/110±11毫米汞柱（P=无统计学意义）。硝苯地平控释片使血压大幅下降的同时，仅治疗2个月后左心室[LV]质量指数就显著降低（从146±40降至129±35克/平方米，P=.05）。相比之下，依那普利对LV质量无影响（从139±36降至142±50克/平方米，P=无统计学意义）。硝苯地平控释片的降压作用在开放期进一步得到证实，在此期间，24小时血压从基线时的180±14/118±6毫米汞柱降至16周开放期末的142±16/92±10毫米汞柱（P<.0001）。这种作用得以持续，收缩压谷峰比为74%，舒张压为67%，LV质量进一步减轻。硝苯地平控释片治疗的患者中，24小时收缩压降至<135毫米汞柱与LV质量指数更大程度的减轻相关。两组不良事件发生率均较低，硝苯地平控释片和依那普利耐受性均良好。显著室性心律失常的发生率也较低，且不随治疗而改变。总之，我们的研究结果表明，基于其显著且持续的降压作用、与左心室质量显著减轻相关以及低副作用 profile，每日一次服用硝苯地平控释片可被视为重度高血压黑人患者合适的一线抗高血压药物。
