Malacco Ettore, Omboni Stefano
Division of Internal Medicine III, L. Sacco Hospital, University of Milano, Milano, Italy.
Italian Institute of Telemedicine, Varese, Italy.
Curr Ther Res Clin Exp. 2008 Jun;69(3):232-42. doi: 10.1016/j.curtheres.2008.06.008.
International guidelines recommend the use of angiotensin-converting enzyme inhibitors, possibly in combination with other antihypertensive drugs, to treat hypertension with associated risk factors.
The aim of this study was to compare the antihypertensive effect of the combination of zofenopril plus hydrochlorothiazide versus zofenopril monotherapy in patients with essential hypertension, according to their cardiovascular risk level.
This was a post hoc analysis of a previously published efficacy and tolerability study. After a 4-week placebo washout, patients with mild to moderate essential hypertension (diastolic blood pressure [DBP] 95-115 mm Hg), aged 18 to 75 years, were randomized at a ratio of 2:1:1 to treatment with zofenopril 30 mg plus hydrochlorothiazide 12.5 mg or monotherapy with zofenopril 30 mg or hydrochlorothiazide 12.5 mg for 12 weeks in an international, multicenter, double-blind study. This period was followed by 24 weeks of open-label treatment. Systolic BP [SBP] and DBP were measured by mercury sphygmomanometry, and changes associated with treatment were calculated. Patients' cardiovascular risk was computed using the Heart Score algorithm. Patients were classified in quartiles according to distribution of cardiovascular risk level, and comparisons were limited to the zofenopril plus hydrochlorothiazide and zofenopril monotherapy treatment groups. The primary end point was change in office DBP.
Two hundred forty-six patients (139 men, 107 women; mean [SD] age, 54 [11] years) were included in the analysis. Mean baseline cardiovascular risk was similar in the zofenopril plus hydrochlorothiazide group and the zofenopril monotherapy group (7% vs 9%). DBP and SBP reductions with treatment were significantly greater (both, P < 0.01) with combination treatment than with monotherapy for each quartile of cardiovascular risk. Cardiovascular risk reduction at the end of the 12 weeks of double-blind treatment was greater in the zofenopril plus hydrochlorothiazide group than in the zofenopril monotherapy group (1.9% vs 0.2%; P < 0.01), particularly in the group of patients with the highest cardiovascular risk at baseline (5.2% vs 2.0%). At the end of the 24-week open-label treatment period, the mean reduction in cardiovascular risk was also significantly greater in the combination treatment group than in the monotherapy group (1.4% vs 0.5%; P < 0.01).
In these hypertensive patients, combination treatment with zofenopril plus hydrochlorothiazide was associated with a significantly greater decrease in BP compared with zofenopril monotherapy, regardless of the patient's cardiovascular risk. The difference between combination treatment and monotherapy was particularly evident for the group of patients at highest risk.
国际指南推荐使用血管紧张素转换酶抑制剂，可能与其他抗高血压药物联合使用，以治疗伴有危险因素的高血压。
本研究的目的是根据心血管风险水平，比较佐芬普利加氢氯噻嗪联合治疗与佐芬普利单药治疗对原发性高血压患者的降压效果。
这是一项对先前发表的疗效和耐受性研究的事后分析。在为期4周的安慰剂洗脱期后，年龄在18至75岁、轻度至中度原发性高血压（舒张压[DBP]95 - 115 mmHg）患者，在一项国际多中心双盲研究中，按2:1:1的比例随机分为接受30 mg佐芬普利加12.5 mg氢氯噻嗪治疗、30 mg佐芬普利单药治疗或12.5 mg氢氯噻嗪单药治疗12周。此阶段之后是24周的开放标签治疗。采用汞柱式血压计测量收缩压[SBP]和舒张压，计算与治疗相关的变化。使用心脏评分算法计算患者的心血管风险。根据心血管风险水平分布将患者分为四分位数，比较仅限于佐芬普利加氢氯噻嗪和佐芬普利单药治疗组。主要终点是诊室舒张压的变化。
246例患者（139例男性，107例女性；平均[标准差]年龄54[11]岁）纳入分析。佐芬普利加氢氯噻嗪组和佐芬普利单药治疗组的平均基线心血管风险相似（7%对9%）。对于每个心血管风险四分位数，联合治疗组治疗后的舒张压和收缩压降低幅度均显著大于（均P < 0.01）单药治疗组。双盲治疗12周结束时，佐芬普利加氢氯噻嗪组的心血管风险降低幅度大于佐芬普利单药治疗组（1.9%对0.2%；P < 0.01），特别是在基线心血管风险最高的患者组中（5.2%对2.0%）。在24周开放标签治疗期结束时，联合治疗组的心血管风险平均降低幅度也显著大于单药治疗组（1.4%对0.5%；P < 0.01）。
在这些高血压患者中，无论患者的心血管风险如何，佐芬普利加氢氯噻嗪联合治疗与佐芬普利单药治疗相比，血压降低幅度显著更大。联合治疗与单药治疗之间的差异在风险最高的患者组中尤为明显。
