Plat F, Saini R
Bristol-Myers Squibb Pharmaceutical Research Institute Europe, Waterloo, Belgium.
Am J Hypertens. 1997 Oct;10(10 Pt 2):262S-271S. doi: 10.1016/s0895-7061(97)00333-6.
The complementary action of angiotensin converting enzyme inhibitors and diuretics in the treatment of hypertension has been demonstrated in a number of studies of fosinopril and hydrochlorothiazide (HCTZ). The combination provides a clinically significant reduction in blood pressure while minimizing the dose-dependent adverse effects of HCTZ, such as hypotension and its metabolic effects on plasma lipoproteins, by keeping the dose of each agent to the minimum. Fosinopril has a unique dual mechanism of elimination and can therefore be used in patients with renal impairment. The efficacy of the combination of fosinopril and hydrochlorothiazide compared with placebo and other agents is reviewed in this article. Studies have demonstrated that the combination is effective in the elderly and in renally impaired patients, regardless of severity. In addition, in non-insulin dependent diabetes, antihypertensive effect is achieved without further affecting carbohydrate and lipid metabolism, which is often the case when thiazide diuretics alone are used. A matrix study was performed to evaluate the optimum dose combination to produce blood pressure normalization and minimize side effects. This study evaluated 17 different dose combinations and demonstrated that the lowest dose combination to produce a clinically significant effect was fosinopril 10 mg and HCTZ 12.5 mg. However, a dose-related antihypertensive effect can be seen, giving the option for the use of 20 mg fosinopril for moderately hypertensive patients. Both combination therapy and fosinopril were significantly more effective than HCTZ alone or placebo. The fosinopril/HCTZ combination has also been shown to have a comparable effect to sustained-release nifedipine and propanolol + HCTZ. The studies reviewed here demonstrate that fosinopril/HCTZ combination treatment has a number of advantages over either agent used alone, providing blood pressure normalization in a broad range of hypertensive patients, including diabetic patients and the elderly.
在多项关于福辛普利和氢氯噻嗪（HCTZ）的研究中，已证实血管紧张素转换酶抑制剂与利尿剂在治疗高血压方面具有协同作用。这种联合用药能显著降低血压，同时通过将每种药物的剂量降至最低，使HCTZ剂量依赖性的不良反应（如低血压及其对血浆脂蛋白的代谢影响）降至最小。福辛普利具有独特的双重消除机制，因此可用于肾功能不全患者。本文综述了福辛普利与氢氯噻嗪联合用药与安慰剂及其他药物相比的疗效。研究表明，无论严重程度如何，该联合用药在老年患者和肾功能不全患者中均有效。此外，在非胰岛素依赖型糖尿病患者中，该联合用药可实现降压效果，且不会进一步影响碳水化合物和脂质代谢，而单独使用噻嗪类利尿剂时往往会出现这种情况。进行了一项矩阵研究，以评估实现血压正常化并使副作用最小化的最佳剂量组合。该研究评估了17种不同的剂量组合，结果表明产生临床显著效果的最低剂量组合是福辛普利10毫克和氢氯噻嗪12.5毫克。然而，可见剂量相关的降压作用，这为中度高血压患者使用20毫克福辛普利提供了选择。联合治疗和福辛普利均比单独使用氢氯噻嗪或安慰剂显著更有效。福辛普利/氢氯噻嗪联合用药也已显示出与硝苯地平缓释片以及普萘洛尔+氢氯噻嗪具有相当的效果。本文综述的研究表明，福辛普利/氢氯噻嗪联合治疗比单独使用任何一种药物都具有许多优势，可为包括糖尿病患者和老年患者在内的广泛高血压患者实现血压正常化。
