Antihypertensive Efficacy of Candesartan in Comparison to Losartan: The CLAIM Study

An 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study was conducted to evaluate the antihypertensive efficacy of candesartan vs. losartan in 654 hypertensive patients with a diastolic blood pressure between 95 and 114 mm Hg from 72 sites throughout the U.S. Eligible patients were randomized to candesartan cilexetil 16 mg once daily, or losartan 50 mg once daily. Two weeks following randomization, patients doubled the respective doses of their angiotensin receptor blockers for an additional 6 weeks. At week 8, candesartan cilexetil lowered trough systolic/diastolic blood pressure by a significantly greater amount than did losartan (13.3/10.9 mm Hg with candesartan cilexetil vs. 9.8/8.7 mm Hg with losartan; p < 0.001). At the same period, candesartan cilexetil also lowered peak blood pressure by a significantly greater amount than did losartan (15.2 to 11.6 mm Hg with candesartan cilexetil vs. 12.6 to 10.1 mm Hg with losartan; p < 0.05). There were statistically significantly ( p < 0.05) higher proportions of responders and controlled patients in the candesartan cilexetil group (62.4% and 56.0%, respectively) than in the losartan group (54.0% and 46.9%, respectively). Both treatment regimens were well tolerated; 1.8% in the candesartan cilexetil group and 1.6% in the losartan group withdrew because of adverse events. In conclusion, this forced-titration study confirms that candesartan cilexetil is more effective than losartan in lowering blood pressure when both are administered once daily at maximum doses. Both drugs were well tolerated.     

Three-Month Effects of Candesartan Cilexetil, an Angiotensin II Type 1 (AT1) Receptor Antagonist, on Left Ventricular Mass and Hemodynamics in Patients with Essential Hypertension

Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2–8 mg/day orally for 8–12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 ± 17.2 mmHg (mean ± SD) to 150.2 ± 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 ± 6.5 mmHg to 87.8 ± 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 ± 31.3 g/m2 to 102.6 ± 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 ± 31.1 g/m2 to 115.8 ± 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 ± 636.3 dynes·s·cm–5 to 1540.4 ± 432.0 dynes·s·cm–5 (P = 0.0034) on MRI and from 1820.4 ± 318.8 dynes·s·cm–5 to 1659.0 ± 317.7 dynes·s·cm–5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2–8 mg/day orally for 8–12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.     

Effect of Losartan, an Angiotensin II Antagonist, on Hepatic Fibrosis Induced by CCl4 in Rats

In addition to regulating blood pressure and body fluid homeostasis, the renin-angiotensin system (RAS) is also involved in hepatic fibrogenesis. We aimed to investigate the effect of losartan, an angiotensin II (Ang II) antagonist, on CCl4-induced hepatic fibrosis in rats. Hepatic fibrosis was induced by a subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. Hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) stimulated with Ang II was determined by ELISA. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin, then scored. Losartan (2.5, 5, and 10 mg x kg(-1), ig) and captopril (100 mg x kg(-1), ig) significantly decreased liver and spleen indexes, serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological scores showed that losartan had an inhibitory effect on the progression of hepatic fibrosis. In in vitro experiments, losartan (1 x 10(-9) - 1 x 10(-5) M) significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs, but captopril (1 x 10(-5) M) did not. The results showed that losartan significantly inhibited the progression of hepatic fibrosis induced by CCl4, and the inhibitory effect of losartan on hepatic fibrosis might be associated with its ability to inhibit the production of TNF-alpha and TGF-beta1 by activated KCs.     

Antihypertensive Efficacy of Olmesartan Medoxomil, a New Angiotensin II Receptor Antagonist, as Assessed by Ambulatory Blood Pressure Measurements

Olmesartan medoxomil is a new angiotensin II receptor blocker. In this randomized, double-blind, placebo-controlled study, the efficacy and safety of olmesartan medoxomil was assessed in 334 patients with moderate to severe essential hypertension. Patients were randomized to receive placebo; 5, 20, or 80 mg olmesartan medoxomil q.d.; or 2.5, 10, or 40 mg olmesartan medoxomil b.i.d. Ambulatory and cuff blood pressure were measured prior to and after 8 weeks of treatment. Treatment with olmesartan medoxomil resulted in a significant placebo-adjusted reduction of mean 24-hour ambulatory diastolic blood pressure of 9.6 mm Hg, 12.2 mm Hg, and 10.6 mm Hg in the 5-, 20-, and 80-mg q.d. groups, respectively. Corresponding reductions in mean ambulatory systolic blood pressure were 14.5 mm Hg, 16.5 mm Hg, and 15.4 mm Hg. Similar reductions of diastolic and systolic blood pressure were seen with b.i.d. dosing. The diastolic trough-to-peak ratios of the q.d. doses of olmesartan medoxomil ranged from 57%–70%, indicating 24-hour effectiveness. The safety profile of olmesartan medoxomil was similar to that of placebo. Olmesartan medoxomil appears to be a safe and effective once-a-day treatment for hypertension.     

坎地沙坦酯联合拉西地平治疗老年性高血压的临床疗效观察

目的观察坎地沙坦酯联合拉西地平治疗老年性高血压的临床疗效及安全性。方法选取2010年12月—2012年12月我院收治的老年性高血压患者84例,将其随机分成对照组和观察组,各42例。对照组应用坎地沙坦酯治疗,观察组应用坎地沙坦酯联合拉西地平治疗,均治疗6周,观察两组治疗效果。结果观察组总有效率为92.9%(39/42),高于对照组的78.6%(33/42)(P0.05);且观察组仅有1例出现脚踝部水肿。结论坎地沙坦酯联合拉西地平治疗老年性高血压有明显的降压疗效,安全可靠,不良反应少,值得临床推广应用。     

Antihypertensive Treatment with Candesartan Cilexetil does not Affect Glucose Homeostasis or Serum Lipid Profile in Patients with Mild Hypertension and Type II Diabetes

This multicentre, randomized, controlled clinical trial assessed the effects of candesartan cilexetil (cand.cil.), a novel angiotensin II antagonist selective for the AT1 receptor with long-lasting antihypertensive activity, compared to placebo on glucose homeostasis and serum lipid profile in mild hypertensives with type II diabetes. A total of 161 men and women, 30-75 years old, with mild hypertension (sitting diastolic blood pressure 90-100 mmHg) and type II diabetes (HbA1c 5.5-9.0%), both measured after a 4-week placebo run-in period, were randomized to double-blind treatment with cand.cil. 8 mg o.i.d. (n = 83) or placebo (n     

Clinical and Experimental Aspects of Olmesartan Medoxomil,a New Angiotensin II Receptor Antagonist

Olmesartan medoxomil is a new orally active angiotensin II (Ang II) type 1 receptor antagonist. It is a prodrug and is rapidly de‐esterified during absorption to form olmesartan, the active metabolite. Olmesartan is a potent, competitive and selective Ang II type 1 receptor antagonist. Olmesartan is not metabolized by the cytochrome P‐450 and has a dual route of elimination, by kidneys and liver. In patients with essential hypertension olmesartan medoxomil administered once daily at doses of 10–80 mg dose‐dependently reduced diastolic blood pressure (DBP). Troughto‐peak ratios for both DBP and systolic blood pressure (SBP) were above 50%. At the recommended once‐daily starting doses, olmesartan medoxomil (20 mg) was more effective than losartan (50 mg), valsartan (80 mg) or irbesartan (150 mg) in reducing cuff DBP in patients with essential hypertension. The results of cuff SBP and mean 24‐h DBP and SBP were similar to those of cuff DBP measurement. In mild‐to‐moderate hypertensive patients the recommended starting dose of olmesartan medoxomil was as effective as that of amlodipine besylate (5 mg/day) in reducing both cuff and 24‐h blood pressure. In lowering DBP olmesartan medoxomil, at 10–20 mg/day, was as effective as atenolol at 50–100 mg/day. In mild‐to‐moderate hypertensive patients, olmesartan medoxomil, at 5–20 mg once daily, was more effective than captopril at 12.5–50 mg twice daily. At 20–40 mg once daily olmesartan medoxomil was as effective as felodipine, at 5–10 mg once daily. Olmesartan medoxomil has minimal adverse effects with no clinically important drug interactions. Animal studies have shown that olmesartan medoxomil provides a wide range of organ protection. Olmesartan medoxomil ameliorated atherosclerosis in hyperlipidemic animals and ameliorated cardiac remodeling and improved survival in rats with myocardial infarction. Olmesartan medoxomil has renoprotective effects in a remnant kidney model and type 2 diabetes models. Future investigation should reveal whether these beneficial effects of olmesartan medoxomil are applicable to human diseases.     

氯沙坦与氨氯地平的降压疗效及其对左心室肥厚逆转作用的效果对比

目的比较氯沙坦与氨氯地平的降压疗效及其对左心室肥厚逆转作用的效果。方法选取2010年5月—2013年4月我社区收治的高血压患者120例,采用随机数字表法将其分为A组和B组,各60例。A组口服氯沙坦钾片治疗,B组口服苯磺酸氨氯地平片治疗,均连续治疗12周。比较两组患者血压和超声心动图指标,包括左心室舒张末内径(LVDd)、舒张期室间隔厚度(LVSd)、左心室后壁厚度(LVPWd)、左心室重量指数(LVMI)。结果治疗后两组收缩压和舒张压比较,差异均无统计学意义(P0.05);A组LVDd、LVSd、LVPWd、LVMI均低于B组(P0.05)。两组不良反应发生率比较,差异无统计学意义(P0.05)。结论氯沙坦与氨氯地平治疗原发性高血压均可获得满意的降压疗效,其中氯沙坦可有效逆转左心室肥厚,疗效具有一定的优越性。     

Angiotensin II-Receptor Antagonist Losartan Does not Prevent Nitroglycerin Tolerance in Patients with Coronary Artery Disease

The study evaluated the effect of Losartan in preventing nitrate tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary disease. Fifteen subjects with chronic stable ischemia evaluated by exercise test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval plus Losartan 100 mg or Losartan-placebo with a double blind crossover design. Myocardial ischemic parameters during stress test were evaluated after each test period and results of Losartan therapy were compared to those with placebo. Time to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or Losartan-placebo (p < 0.001). ST-depression at peak exercise and time to recovery of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo run-in (p < 0.05), sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001) or Losartan-placebo (p < 0.05). At 1 mm-ST depression and at peak exercise, systolic blood pressure and rate-pressure product significantly decreased after sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001, p < 0.05 respectively) with respect to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo. Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo (p < 0.001). The AT₁ antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy.     

Inhibition of Induced Aldosterone Biosynthesis with a Specific Antagonist of Angiotensin II

The present study determined the effect of [Sar(1)-Ile(8)]-angiotensin II on steroidogenesis and induced aldosterone synthesis by the octapeptide angiotensin II, the heptapeptide des-Asp(1)-angiotensin II, and adrenocorticotropic hormone. Rabbit adrenal cells were suspended by incubation of the capsular cortical tissue with collagenase, and aldosterone levels were determined by immunoassay. Steroidogenic responses to angiotensin II and des-Asp(1)-angiotensin were essentially the same. [Sar(1)-Ile(8)]-angiotensin II (10(-7) to 5 x 10(-7) M) had no significant effect on basal aldosterone biosynthesis. However, when added with steroidogenic peptides, it completely blocked the effect of angiotensin II and des-Asp(1)-angiotensin II but not of adrenocorticotropic hormone. The dose ratio of the antagonist to angiotensin II that gave 100% inhibition was about 2:1 and to des-Asp(1)-angiotensin II, about 50:1. The data suggest that des-Asp(1)-angiotensin II has a much higher affinity for the angiotensin receptor in adrenal cortex than angiotensin II.     

国产坎地沙坦酯片治疗轻中度原发性高血压的疗效和安全性

目的　评价坎地沙坦酯片治疗轻中度原发性高血压的疗效和安全性。方法　随机、双盲、双模拟、阳性药物 (氯沙坦 )平行对照。 6 1例轻、中度原发性高血压服用坎地沙坦酯片或氯沙坦片各 1片 ,1次 /d ,必要时增加剂量 1次。总疗程 8周。结果　氯沙坦组治疗前的血压为 (14 6 .2±11.6 ) / (10 0 3± 3.3)mmHg,治疗后的血压为 (130 3± 9.8) / (85 .7± 8 0 )mmHg,血压下降幅度为(16 0± 11.8) / (14 .6± 6 .8)mmHg;坎地沙坦酯组治疗前的血压为 (14 3.4± 11.2 ) / (10 0 6± 4 .1)mmHg,治疗后的血压为 (130 4± 11.2 ) / (86 .3± 8 0 )mmHg,血压下降幅度为 (13 0± 8.7) / (14 .3±6 .5 )mmHg。两组治疗后血压降低幅度均有统计学意义 ,主要降幅均在前 2周。组间无差异。治疗前后心率无明显变化。坎地沙坦酯和氯沙坦降压显效率分别为 6 0 7%和 6 0 0 % ,总有效率分别为82 .1%和 76 .7% ,组间无差别。不良事件坎地沙坦酯和氯沙坦组为头晕各 2例和 1例 ,血生化等实验室指标无异常改变。结论　国产坎地沙坦酯片治疗轻中度原发性高血压不良反应发生率很低 ,本文无 1例出现咳嗽 ,耐受性良好 ,适用于长期治疗。     

国产坎地沙坦酯片治疗轻中度原发性高血压的疗效和安全性

目的评价坎地沙坦酯片治疗轻中度原发性高血压的疗效和安全性.方法随机、双盲、双模拟、阳性药物(氯沙坦)平行对照.61例轻、中度原发性高血压服用坎地沙坦酯片或氯沙坦片各1片,1次/d,必要时增加剂量1次.总疗程8周.结果氯沙坦组治疗前的血压为(146.2±11.6)/(100.3±3.3)mm Hg,治疗后的血压为(130.3±9.8)/(85.7±8.0)mm Hg,血压下降幅度为(16.0±11.8)/(14.6±6.8)mm Hg;坎地沙坦酯组治疗前的血压为(143.4±11.2)/(100.6±4.1)mm Hg,治疗后的血压为(130.4±11.2)/(86.3±8.0)mm Hg,血压下降幅度为(13.0±8.7)/(14.3±6.5) mm Hg.两组治疗后血压降低幅度均有统计学意义,主要降幅均在前2周.组间无差异.治疗前后心率无明显变化.坎地沙坦酯和氯沙坦降压显效率分别为60.7%和60.0%,总有效率分别为82.1%和76.7%,组间无差别.不良事件坎地沙坦酯和氯沙坦组为头晕各2例和1例,血生化等实验室指标无异常改变.结论国产坎地沙坦酯片治疗轻中度原发性高血压不良反应发生率很低,本文无1例出现咳嗽,耐受性良好,适用于长期治疗.     

Efficacy of Irbesartan, a Receptor Selective Antagonist of Angiotensin II, in Reducing Portal Hypertension

The use of angiotensin II antagonists in the treatment of portal hypertension remains controversial. Our aims were to assess the effect of Irbesartan on portal pressure and to evaluate its safety in cirrhotic patients with portal hypertension. Twenty-five cirrhotic patients were treated in a pilot study with Irbesartan 300 mg orally once daily for 60 days. Hemodynamic evaluations and biochemical tests were performed before therapy and after two months of treatment. Three patients (12%) discontinued treatment for symptomatic arterial hypotension (mean arterial pressure –26.% ± 3.1 versus basal). In the 18 responders, the hepatic venous pressure gradient diminished by a mean of 18.1% ± 10.5 from baseline (p = 0.02); the gradient decreased by 20% or more in only 5 patients (23%). The mean arterial pressure decreased significantly during therapy (92 ± 7 vs 109 ± 25 mm Hg, P < 0.001). In conclusions, Irbesartan induced a marginal reduction in portal pressure and its safety was limited by the pronounced effects on arterial pressure.     

Design and baseline characteristics of an observational study in Japanese patients with hypertension: Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH).

The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study is a nationwide, prospective, multicenter observational study that was designed to enroll hypertensive Japanese patients (>30,000 subjects). The patients in this study received treatment with open-label losartan, an angiotensin II receptor antagonist, for a maximum of 5 years. This report summarizes the study protocol and the baseline characteristics of the patients. Between June 2000 and May 2002, patients were screened in all 47 prefectures around Japan. Among the 31,515 patients screened, 31,048 patients were enrolled in this study and treated with losartan at a daily dose of 25-50 mg. These patients were 62.4 +/- 12.1 years old (mean +/- SD) and the mean clinic systolic/diastolic blood pressure (BP) values were 165.3 +/- 17.3/94.3 +/- 11.7 mmHg (mean +/- SD). The complications of hyperlipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease were also present in 38.5%, 13.1%, 8.0%, and 4.4% of patients, respectively. Regarding the World Health Organization classification, grade 2 hypertension was most frequent in this patient cohort. Nearly 10,000 patients agreed to perform home BP monitoring and report details regarding their lifestyles at baseline. Among the patients, 4.2% had white coat hypertension at the baseline. The J-HEALTH study is expected to provide valuable information about the significance of clinic and home BP control and home BP monitoring for the management of hypertension in Japanese patients.     

Effect of a reduction in uric acid on renal outcomes during losartan treatment: a post hoc analysis of the reduction of endpoints in non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan Trial

Emerging data show that increased serum uric acid (SUA) concentration is an independent risk factor for end-stage renal disease. Treatment with the antihypertensive drug losartan lowers SUA. Whether reductions in SUA during losartan therapy are associated with renoprotection is unclear. We therefore tested this hypothesis. In a post hoc analysis of 1342 patients with type 2 diabetes mellitus and nephropathy participating in the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan Trial, we determined the relationship between month 6 change in SUA and renal endpoints, defined as a doubling of serum creatinine or end-stage renal disease. Baseline SUA was 6.7 mg/dL in placebo and losartan-treated subjects. During the first 6 months, losartan lowered SUA by -0.16 mg/dL (95% CI: -0.30 to -0.01; P=0.031) as compared with placebo. The risk of renal events was decreased by 6% (95% CI: 10% to 3%) per 0.5-mg/dL decrement in SUA during the first 6 months. This effect was independent of other risk markers, including estimate glomerular filtration rate and albuminuria. Adjustment of the overall treatment effects for SUA attenuated losartan's renoprotective effect from 22% (95% CI: 6% to 35%) to 17% (95% CI: 1% to 31%), suggesting that approximately one fifth of losartan's renoprotective effect could be attributed to its effect on SUA. Losartan lowers SUA levels compared with placebo treatment in patients with type 2 diabetes mellitus and nephropathy. The degree of reduction in SUA is subsequently associated with the degree in long-term renal risk reduction and explains part of losartan's renoprotective effect. These findings support the view that SUA may be a modifiable risk factor for renal disease.     

In Vivo Pharmacology of L-159,913, A New Highly Potent and Selective Nonpeptide Angiotensin II Receptor Antagonist

The present study was designed to characterize the in vivo pharmacology of L-159,913 (4-[[2′-(N-benzoylsulfamoyl)biphenyl-4-yl]-5butyl-2,4-dihydro-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazcl-3-one); a potent All receptor antagonist. In normotensive rats, dogs, rhesus monkeys, and chimpanzees, L-159,913 inhibited All-induced elevations in blood pressure. In conscious rats, the relative potencies (ED₅₀) were 0.51 mg/kg i.v. and 0.72 mg/kg p.o. Duration of action with single i.v. or p.o. doses exceeded 6 hr in rats. L-159,913 was 3 times less potent than losartan in rats and equipotent to losartan in monkeys. All induced elevation of plasma aldosterone in rats was also inhibited by L-159,913. L-159,913 was antihypertensive in high renin hypertensive rats (aortic coarctation). The maximum hypotensive response to an acute dose of L-159,913 (10 mg/kg, PO) was equal to that of enalaprilat (0.3 mg/kg, iv) in this renin dependent animal model. In conscious normotensive dogs, L-l59,913 had a moderate diuretic, natriuretic and kaliuretic response with no effect on glomerular filtration rate, effective renal plasma flow or filtration fraction, suggesting a tubular site of action. L-159,913 is a selective and potent All receptor antagonist with good oral activity, long duration of action and antihypertensive efficacy.     

无创性动态血压监测评价复方坎地沙坦酯片治疗原发性高血压患者的疗效

目的用无创性动态血压监测仪评价国产复方坎地沙坦酯片(坎地沙坦酯16 mg/氢氯噻嗪12.5 mg)对原发性高血压患者的降压疗效.方法原发性高血压患者经过2周清洗期后,进入坎地沙坦酯片8 mg单药治疗期,对4周后坐位血压未达标者(达标为血压＜140/90 mmHg),进行24小时动态血压监测,以随机双盲、平行对照试验方法,分别服用复方坎地沙坦酯片(复方坎地沙坦酯组,28例)或16 mg坎地沙坦酯片(坎地沙坦酯组,27例)治疗8周.比较两组服药前后24小时动态血压参数变化.观察组内与组间服药前后的不同时段的血压变化,谷峰比值及血压平滑指数.结果共55例患者完成动态血压监测,两组基础指标比较无差异.复方坎地沙坦酯组与坎地沙坦酯组药后收缩压/舒张压/平均动脉压全日平均值(24小时)、日间平均值(600～2200)、夜间平均值(2200～600)均明显下降,与同组基线值比较均有极显著性差异(P＜0.01).组间比较,复方坎地沙坦酯组收缩压/舒张压/平均动脉压全日平均值(24小时)、日间平均值(600～2200)、夜间平均值(2200～600)的降低幅度与坎地沙坦酯组比较均有极显著性差异(P＜0.01).服药谷峰比值(SBP/DBP)复方坎地沙坦酯组分别为99.36%(19.16/19.28 mmHg)和87.36%(10.14/11.61 mmHg),复方坎地沙坦酯组分别为54.42%(7.30/13.41 mmHg)和64.86%(6.43/9.91 mmHg).血压平滑指数(SBP/DBP)在复方坎地沙坦酯组为4.53/3.91,坎地沙坦酯组为1.29/1.52.结论复方坎地沙坦酯片对原发性高血压患者有较好的降压作用,复方制剂比单药降压幅度大、持续时间长.动态血压平均下降幅度日间＞全天＞夜间,收缩压＞舒张压.复方坎地沙坦酯控制血压更平稳.     

Efficacy and Duration of Action of the Four Selective Angiotensin II Subtype 1 Receptor Blockers,Losartan, Candesartan,Valsartan and Telmisartan,in Patients with Essential Hypertension Determined by Home Blood Pressure Measurements

Our objective was to compare the efficacy and duration of action of 4 angiotensin II receptor blockers (ARBs)—losartan (25–100 mg), candesartan (2–12 mg), valsartan (40–80 mg), and telmisartan (10–40 mg)—in patients with essential hypertension using self-measurement of blood pressure at home (home BP) and to examine the differential effect of the four ARBs on home pulse pressure (home PP). After a 2-week run-in period, each of the 4 ARBs was assigned to subjects who were diagnosed as having hypertension on the basis of home BP and who were over 30 years old. The subjects were asked to take the ARB once daily in the morning and to measure home BP once in the evening and in the morning. We compared the efficacy of each ARB on home BP and home PP and assessed the duration of the BP-lowering effect using the morning effect versus evening effect ratio (M/E ratio). The antihypertensive effects of telmisartan on home systolic BP (SBP) both in the evening and in the morning and on home diastolic BP (DBP) in the morning were significantly greater than those of losartan. The effect of each ARB on home BP in the morning and in the evening was expressed as a ratio (M/E ratio). The M/E ratios of SBP/DBP in patients treated with losartan, candesartan, valsartan, and telmisartan were 0.49/0.16, 0.69/1.01, 0.82/0.88, and 0.88/0.88, respectively. The home PP-lowering effect was greater for valsartan and telmisartan than for losartan and candesartan in the morning. Among the 4 ARBs, the duration of the BP-lowering effect of losartan did not persist throughout 24 hr. The effects of the other 3 ARBs, in particular telmisartan, persisted over 24 hr when they were administered once daily in the morning. In addition, the duration of the PP-lowering effect was similar to that of the BP-lowering effect. Such long-acting property of several ARBs is essential for the modern antihypertensive treatment, and home BP measurements are useful for determining the duration of action of antihypertensive drugs. Losartan, 25 mg a day, which is usually used as an initial dose in Japan, is apparently insufficient to obtain adequate antihypertensive effect and sufficient duration of action.     

GNB3基因C825T多态性与中国高血压患者服用坎地沙坦酯或坎地沙坦酯／氢氯噻嗪复方制剂降压疗效的相关性研究

目的探讨GNB3C825T基因多态性与坎地沙坦酯及复方坎地沙坦酯（坎地沙坦酯＋氢氯噻嗪）降压疗效的相关性。方法62名原发性高血压患者随机分组，分别给予坎地沙坦酯片及坎地沙坦酯＋氢氯噻嗪片治疗8周，定期随访取得血压下降数据。采用聚合酶链式反应．限制性片断长度多态性（PCR-RFLP）方法检测GNB3基因型。利用协方差分析各基因型与两药物降压疗效的关系。结果服用坎地沙坦酯／氢氯噻嗪复方的病人血压下降值明显高于单独服用坎地沙坦酯的病人血压下降值（P〈0．05）。GNB3825T等位基因在入选的高血压病人中频率为45．16％。与多数国人报道结果一致。协方差分析结果显示服用两种药后收缩压和舒张压的下降幅度在GNB3C825T各基因型高血压患者问比较均无统计学差异（P〉0．05）。结论GNB3C825T基因多态性可能与坎地沙坦酯及坎地沙坦酯＋氢氯噻嗪降压疗效不相关。