Okin S, Huberfeld S I, Frishman W H, Soberman J, Laifer L, Greenberg S, Lapsker J, Charlap S, Strom J A
Department of Medicine, the Albert Einstein College of Medicine, Bronx, New York.
J Clin Pharmacol. 1988 Nov;28(11):1008-16. doi: 10.1002/j.1552-4604.1988.tb03122.x.
The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.
采用安慰剂导入、随机、双盲平行研究设计,对33例轻至中度高血压患者(坐位舒张压[DBP]95 - 115 mmHg)比较了竞争性5-羟色胺阻断剂酮色林与普萘洛尔的安全性和有效性。所有患者接受4周安慰剂治疗,然后随机接受递增剂量的酮色林(每日2次,每次20、40 mg)或普萘洛尔(每日2次,每次40、80 mg),以使坐位DBP目标值低于90 mmHg。单药治疗未达到目标血压的患者,接受另一种药物联合治疗。在活性单药治疗阶段结束时(研究第10周),与酮色林相比,普萘洛尔使DBP较基线有更大幅度下降(普萘洛尔组为-7.9±10.9 mmHg,P<0.05;酮色林组为-1.0±7.2 mmHg,P=无统计学意义)。16例接受普萘洛尔治疗的患者中有4例达到目标反应,而接受酮色林治疗的17例患者中有3例达到目标反应。联合治疗时,18例患者中有9例达到目标反应;在无反应者中,酮色林加用普萘洛尔使坐位DBP较单药治疗进一步降低-10.3±6.3(P<0.001),而无反应者加用酮色林对坐位DBP无显著反应。普萘洛尔在减慢心率方面显示出持续的效果。酮色林的副作用比普萘洛尔少。对于轻至中度高血压患者,每日2次使用普萘洛尔似乎比每日2次使用酮色林更有效。