Pesant Y, Marc-Aurèle J, Bielmann P, Alaupovic P, Cartier P, Bichet D, Thibault G, Lupien P J
Hôtel-Dieu Hospital, St-Jérôme, QC, Canada.
Am J Ther. 1999 May;6(3):137-47. doi: 10.1097/00045391-199905000-00004.
This was a double-blind, randomized, two-center, active-controlled, prospective, parallel study designed to evaluate the effects of nebivolol at daily doses of 5 mg on lipid and carbohydrate metabolism and on blood pressure in comparison with atenolol at daily doses of 50 mg. Normometabolic subjects with mild-to-moderate essential hypertension were recruited for this study, which included a 4-week, single-blind placebo washout phase and a 12-week double-blind treatment phase. After 12 weeks of treatment, both drugs demonstrated a significant decrease from baseline in high-density lipoprotein (HDL) apolipoprotein A-I (HDL-apoA-I) (nebivolol, P <.02; atenolol, P <.05). A significant reduction in HDL cholesterol (HDL-C) from baseline was also observed with nebivolol (P <.05). There were no significant differences between the drugs for these parameters, and the ratio low-density lipoprotein cholesterol (LDL-C)-to-HDL-C did not change significantly after 12 weeks of active treatment with nebivolol or atenolol. There were no significant changes in total cholesterol, HDL (2) -C, HDL (3) -C, LDL-C, very-low-density lipoprotein cholesterol (VLDL-C), total triglycerides, HDL-triglycerides (TG), LDL-TG, VLDL-TG, total apoB, LDL-B, VLDL-B (including the ratio LDL-C-to-LDL-apoB), or Lp(a) during treatment with both drugs. No significant differences in plasma apoA-I and apoC-III as well as in apoA-I-, C-III-containing lipoprotein particles (including the apoC-III ratio) were observed between the drugs, neither before nor after each active treatment. There were no significant differences between the drugs or within each treatment group in plasma glucose, insulin, or C-peptide concentrations after a 2-hour oral glucose tolerance test. Mean clinic trough sitting systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 150/98 mm Hg at baseline to 141/90 mm Hg at termination for nebivolol and from 160/99 mm Hg at baseline to 145/88 mm Hg at termination for atenolol. No significant between-treatment differences were observed for the mean clinic trough sitting SBP/DBP. Both drugs significantly increased the atrial natriuretic factor (ANF) N-terminal plasma levels, whereas no changes were observed in ANF C-terminal plasma concentrations. A significant decrease (P <. 05) in the plasma adrenocorticotropic hormone levels was observed after administration of both drugs. A significant decrease (P <.05) in plasma cortisol levels was observed only after atenolol treatment. The incidence of adverse events reported during nebivolol treatment was comparable to that observed during atenolol treatment. Heart rate was significantly reduced by both drugs. There were no significant changes in hematology, biochemistry, or urinalysis studies. Neither nebivolol nor atenolol adversely affected lipid or carbohydrate metabolism in normometabolic hypertensive patients. Both treatments demonstrated adequate and similar antihypertensive effects and were well tolerated.
这是一项双盲、随机、双中心、活性药物对照、前瞻性平行研究,旨在评估每日剂量5 mg奈必洛尔与每日剂量50 mg阿替洛尔相比,对脂质和碳水化合物代谢以及血压的影响。本研究招募了患有轻至中度原发性高血压的正常代谢受试者,研究包括为期4周的单盲安慰剂洗脱期和为期12周的双盲治疗期。治疗12周后,两种药物均使高密度脂蛋白(HDL)载脂蛋白A-I(HDL-apoA-I)较基线水平显著降低(奈必洛尔,P<.02;阿替洛尔,P<.05)。奈必洛尔治疗后,HDL胆固醇(HDL-C)较基线水平也显著降低(P<.05)。这些参数在两种药物之间无显著差异,且在接受奈必洛尔或阿替洛尔12周活性治疗后,低密度脂蛋白胆固醇(LDL-C)与HDL-C的比值无显著变化。在两种药物治疗期间,总胆固醇、HDL(2)-C、HDL(3)-C、LDL-C、极低密度脂蛋白胆固醇(VLDL-C)、总甘油三酯、HDL-甘油三酯(TG)、LDL-TG、VLDL-TG、总载脂蛋白B、LDL-B、VLDL-B(包括LDL-C与LDL-apoB的比值)或脂蛋白(a)均无显著变化。在每次活性治疗前后,两种药物在血浆载脂蛋白A-I和载脂蛋白C-III以及含载脂蛋白A-I、C-III的脂蛋白颗粒(包括载脂蛋白C-III比值)方面均未观察到显著差异。在2小时口服葡萄糖耐量试验后,两种药物之间以及各治疗组内的血浆葡萄糖、胰岛素或C肽浓度均无显著差异。奈必洛尔治疗组的平均诊室谷值坐位收缩压(SBP)/舒张压(DBP)从基线时的150/98 mmHg显著降至治疗结束时的141/90 mmHg,阿替洛尔治疗组从基线时的160/99 mmHg显著降至治疗结束时的145/88 mmHg。两种药物在平均诊室谷值坐位SBP/DBP方面未观察到显著的组间差异。两种药物均显著提高了心钠素(ANF)N端血浆水平,而ANF C端血浆浓度未观察到变化。两种药物给药后,血浆促肾上腺皮质激素水平均显著降低(P<.05)。仅在阿替洛尔治疗后,血浆皮质醇水平显著降低(P<.05)。奈必洛尔治疗期间报告的不良事件发生率与阿替洛尔治疗期间观察到的相当。两种药物均使心率显著降低。血液学、生物化学或尿液分析研究均无显著变化。奈必洛尔和阿替洛尔均未对正常代谢的高血压患者的脂质或碳水化合物代谢产生不良影响。两种治疗均显示出充分且相似的降压效果,耐受性良好。