Bramlage Peter, Buhck Hartmut, Zemmrich Claudia
Institut für Pharmakologie und präventive Medizin, Menzelstrasse 21, 15831, Mahlow, Germany,
Clin Drug Investig. 2014 Apr;34(4):241-9. doi: 10.1007/s40261-014-0169-2.
Safety and efficacy of the fixed-dose combination candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg has been demonstrated in a number of randomized clinical trials. Because stringent inclusion and exclusion criteria prohibit many high-risk patients from being investigated in clinical trials we aimed to assess the effectiveness, tolerability, and safety in a large unselected cohort of high-risk patients in primary care. The primary objective was the efficacy of candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg in lowering the office-based blood pressure (BP). Secondary objectives were changes of metabolic parameters and safety.
A multicenter, non-interventional study of patients with a BP ≥ 140 mmHg systolic and/or 90 mmHg diastolic and additional cardiovascular risk factors. Patients received the fixed-dose combination of candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg for 24 weeks.
A total of 3,390 patients with a mean age of 61.7 ± 10.6 years, 57.8 % being male, and a mean body mass index of 29.7 kg/m(2) were documented. Of these, 70.9 % had at least one additional cardiovascular risk factor such as coronary artery disease (45.5 %) or diabetes mellitus (44.5 %). Baseline BP was 159.6 ± 15.3 over 93.5 ± 9.5 mmHg. BP at 24 weeks was reduced by 32.3 ± 15.8 systolic and 16.1 ± 10.2 mmHg diastolic compared with baseline (p < 0.001 each). Systolic BP (SBP) and diastolic BP (DBP) was normalized (<140/<90 mmHg) in 57.4 % of non-diabetic patients. An SBP <140 mmHg or SBP reduction of ≥ 20 mmHg was achieved by 77.9 % non-diabetic patients. Fasting plasma glucose (-5.9 mg/dL), glycosylated hemoglobin (-0.18 %), low-density lipoprotein cholesterol (-8.5 mg/dL) and triglycerides (-20.3 mg/dL) were reduced significantly, high-density lipoprotein was increased by 0.18 %, while potassium and creatinine levels remained stable. The proportion of patients with adverse drug reactions (ADRs) was 1.3 % (n = 61 events in 45 patients). There were ten serious ADRs in eight patients; four patients died without causal relationship to study drug.
The results confirm previous randomized clinical trial data supporting the effectiveness, tolerability, and safety of this fixed-dose combination in an unselected patient population with high cardiovascular risk.
在多项随机临床试验中已证实坎地沙坦酯32毫克/氢氯噻嗪25毫克固定剂量复方制剂的安全性和有效性。由于严格的纳入和排除标准使许多高危患者无法纳入临床试验进行研究，因此我们旨在评估在基层医疗中一大群未经筛选的高危患者中的有效性、耐受性和安全性。主要目的是坎地沙坦酯32毫克/氢氯噻嗪25毫克降低诊室血压（BP）的疗效。次要目的是代谢参数的变化和安全性。
一项针对收缩压≥140毫米汞柱和/或舒张压≥90毫米汞柱且伴有其他心血管危险因素患者的多中心、非干预性研究。患者接受坎地沙坦酯32毫克与氢氯噻嗪25毫克的固定剂量复方制剂治疗24周。
共记录了3390例患者，平均年龄61.7±10.6岁，男性占57.8%，平均体重指数为29.7千克/米²。其中，70.9%的患者至少有一种其他心血管危险因素，如冠状动脉疾病（45.5%）或糖尿病（44.5%）。基线血压为收缩压159.6±15.3毫米汞柱，舒张压93.5±9.5毫米汞柱。与基线相比，24周时收缩压降低了32.3±15.8毫米汞柱，舒张压降低了16.1±10.2毫米汞柱（每项p<0.001）。57.4%的非糖尿病患者收缩压（SBP）和舒张压（DBP）恢复正常（<140/<90毫米汞柱）。77.9%的非糖尿病患者收缩压<140毫米汞柱或收缩压降低≥20毫米汞柱。空腹血糖（-5.9毫克/分升）、糖化血红蛋白（-0.18%）、低密度脂蛋白胆固醇（-8.5毫克/分升）和甘油三酯（-20.3毫克/分升）显著降低，高密度脂蛋白升高了0.18%，而钾和肌酐水平保持稳定。药物不良反应（ADR）患者比例为1.3%（45例患者发生61起事件）。8例患者出现10起严重ADR；4例患者死亡，与研究药物无因果关系。
结果证实了先前随机临床试验数据，支持该固定剂量复方制剂在未经筛选的高心血管风险患者群体中的有效性、耐受性和安全性。
