Efficacy and safety of delapril plus manidipine compared with enalapril plus hydrochlorothiazide in mild to moderate essential hypertension: results of a randomized trial

BACKGROUND: The use of combination therapy is required to achieve blood pressure targets in 40% to 75% of patients with hypertension. There have been few studies comparing the efficacy and tolerability of the new fixed combination of the angiotensin-converting enzyme (ACE) inhibitor delapril 30 mg and the calcium channel antagonist manidipine 10 mg with those of a standard combination of another ACE inhibitor and a diuretic. OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy and tolerability of delapril 30 mg given alone or with manidipine 10 mg with those of enalapril 20 mg given alone or with hydrochlorothiazide (HCTZ) 12.5 mg in patients with mild to moderate essential hypertension. METHODS: This was a multicenter, active-controlled, parallel-group trial. After an initial 2-week placebo run-in period, patients aged 18 to 75 years with diastolic blood pressure (DBP) > or =90 and < or =109 mm Hg were randomized in a 2:1 ratio to receive delapril or enalapril for 8 weeks. After the initial 8 weeks, nonresponders (DBP > or =85 mm Hg) received an additional 8 weeks of treatment with a fixed combination of delapril + manidipine or enalapril + HCTZ; patients whose DBP was normalized continued their initial monotherapy through the end of the study. The primary efficacy variable was the change in sitting DBP at the end of treatment. Secondary efficacy variables were the percentage of patients whose DBP was normalized (DBP Z:85 mm Hg) and the percentage of responders (> or =10-mm Hg reduction in DBP or DBP <85 mm Hg). RESULTS: One hundred sixty patients (84 men, 76 women) were randomized to receive delapril (n = 106) or enalapril (n = 54). After 16 weeks of treatment, the mean (SD) reduction in DBP was similar with the 2 treatments (delapril, -14 [8] mm Hg; enalapril, -15 [8] mm Hg). In the delapril and enalapril groups, DBP was normalized in a respective 55 (51.9%) and 29 (53.7%) patients, and 77 (72.6%) and 38 (70.4%) were responders; there was no significant difference between groups. Tolerability was also similar in both groups--10 (9.4%) patients in the delapril group and 5 (9.3%) in the enalapril group experienced adverse events that were judged related to treatment. CONCLUSIONS: The results of this study suggest that delapril alone or combined with manidipine is well tolerated and as effective as enalapril alone or combined with HCTZ in lowering blood pressure in patients with mild to moderate essential hypertension.     

Effects of manidipine and delapril on serum lipids, lipoproteins, and apolipoproteins in patients with mild to moderate essential hypertension: a randomized trial with one-year follow-up.

Forty-five patients with mild to moderate essential hypertension were randomly assigned to receive 10 to 40 mg of manidipine HCl or 15 to 60 mg of delapril daily for 12 months. In the manidipine-treated group were 13 women and 5 men (mean age, 48.2 years) and in the delapril-treated group 11 women and 11 men (mean age, 53.7 years). Blood samples were taken at baseline and after 6 and 12 months of treatment and again at 2 months after treatment discontinuation. Significant reductions in blood pressure were observed in both treatment groups. The reduction in diastolic blood pressure was significantly greater in the manidipine-treated patients than in the delapril-treated patients; no significant between-groups differences in systolic blood pressure were noted. Heart rate increased significantly in the manidipine group. No changes in serum levels of total cholesterol, triglycerides, and high-density and low-density lipoprotein cholesterol were noted during or after treatment. In the manidipine group, a small but significant decrease in apolipoprotein (apo) A-I and an increase in lipoprotein(a) were found at 6 months and a significant increase in apo A-II and apo E at 12 months; in the delapril group a significant decrease in apo A-I was found at 6 months. The results indicate that both manidipine and delapril are lipid-neutral antihypertensive drugs, since neither drug greatly affected serum lipid metabolism.     

Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension

This 12-week randomized, parallel-group, multicenter study compared fixed combinations of delapril (D) 30 mg plus indapamide (I) 2.5 mg and fosinopril (F) 20 mg plus hydrochlorothiazide (H) 12.5 mg in 171 adult patients with mild to moderate essential hypertension. After a 2-week placebo run-in, sitting and standing systolic (SBP) and diastolic blood pressure (DBP) was measured by conventional sphygmomanometry. The primary efficacy endpoint was the percentage of normalized (sitting DBP ≤90 mm Hg) and responder (sitting DBP reduction of ≥10 mm Hg or DBP ≤90 mm Hg) patients. Treatment effects were analyzed in the intention-to-treat (ITT; n = 171) and the per-protocol (PP; n = 167) populations. The percentage of normalized and responder patients did not differ significantly between the D + I (87.4% and 92%) and the F + H (81% and 86.9%) ITT groups. Similar results were seen in the PP population. In ITT and PP patients, sitting and standing SBP and DBP values were comparable at baseline in the two groups and were significantly (P<.01) and similarly reduced at weeks 4, 8, and 12. Neither treatment induced reflex tachycardia, and both regimens were well tolerated. Four patients in the F + H group dropped out because of adverse events. In this study, the efficacy and safety of D + I were comparable to those of F + H in patients with mild to moderate essential hypertension.     

缬沙坦治疗轻、中度原发性高血压的临床研究——附117例报告

目的：评价缬沙坦治疗轻、中度原发性高血压的临床疗效及安全性。方法：缬沙坦组（５９例,８０ｍｇ／ｄ及１６０ｍｇ／ｄ）和氯沙坦组（对照组,５８例,５０ｍｇ／ｄ至１００ｍｇ／ｄ）均边续服药半年。结果：两组总有效率、降压幅度、收缩压和舒张压的谷／峰比值分别为７５％和７４％、３．５ｋＰａ／２．０ｋＰａ和３．４ｋＰａ／２．１ｋＰａ、０．８２和０．８１、０．７８和０．７９,组间比较均无显著性差异（Ｐ〉０．０５）;两组治疗后血浆贤素活性、血管紧张素Ⅱ均升高（Ｐ〈０．０５～０．０１）;醛固酮、内皮素均降低（均为Ｐ〈０．０５）,但组间比较无显著性差异（Ｐ〉０．０５）。血尿酸也明显下降（均为Ｐ〈０．０５）,基础值越高,降幅越大,且氯沙坦组更显著（Ｐ〈０．０５）。随访半年,两组心、脑血管事件发生率相似（Ｐ〉０．０５）,两组不良反应轻微     

Effect of captopril on high-density lipoprotein subfractions in patients with mild to moderate essential hypertension

Changes in serum lipids, apolipoproteins, and lipoproteins including high-density lipoprotein (HDL) subfractions following administration of captopril in patients with hypertension were studied. Captopril (25 mg twice daily) was administered over a 12-week period to 17 patients with mild to moderate essential hypertension. Captopril was observed to significantly reduce both systolic and diastolic blood pressure, as well as to increase HDL2- cholesterol (HDL2-C) and to decrease HDL3-cholesterol (HDL3-C); however, no significant changes in total HDL-C were recognized. Total cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apo A-II, apo B, apo C-II, apo C-III, and apo E did not change significantly. It is suggested that captopril monotherapy produces a favorable effect on HDL subfractions.     

氨氯地平对轻、中度高血压病人血管内皮功能的影响

目的　探讨 5～ 10mg氨氯地平对轻、中度高血压患者用药前、后血管内皮功能的影响。方法　选 18～70岁轻、中度原发性高血压 (收缩压 <180mmHg ,舒张压 90～ 10 9mmHg)患者 40例。每例患者经 2周的安慰剂清洗期后开始口服氨氯地平 ,每天一次 ,每次 5mg ;服药 4周后降压效果满意 (舒张压 <90mmHg) ,则继续原剂量服药至8周末 ;若服药 4周后舒张压≥ 90mmHg ,则剂量加倍至 8周末。所有病人在安慰剂清洗期末及 8周末用超声测定肱动脉内径的方法测定动脉内皮依赖性血管扩张 (Flow -MediatedDilatation ,FMD)和非内皮依赖性血管扩张 ,即对舌下含服硝酸甘油 0 6mg的反应 (Nitroglycerin -mediatedDilatation ,ND) ,以评价血管内皮功能。结果　 40例患者服药后平均收缩压及舒张压较服药前均轻度下降 (14 3 44± 16 44mmHgvs 14 0 0 7± 17 3 2mmHg ,95 48± 8 5 2mmHgvs 92 0 7±9 3 3mmHg) ,但未达统计学差异 (P =0 40 5 ,P =0 0 62 )。服药后FMD、ND较服药前有所改善 (7 3 7%± 4 0 1%vs 6 61% ,14 49± 8 3 7vs 13 3 1± 5 16) ,差异均未达显著性 (P =0 3 2 7,P =0 490 )。结论　氨氯地平降压作用平缓、安全 ,耐受性好。用药后血管内皮功能 (FMD和ND)有改善趋势 ,以FMD较明显 ,但未达显著性差异     

氯沙坦治疗轻中度原发性高血压病的临床研究：附57例报告

目的：探讨氯沙坦治疗轻、中度原发性高血压病的临床疗效。方法：１１３例原发性高血压患者随机分为两组,氯沙坦组（治疗组,５７例）：５０￣１００ｍｇ／ｄ口服,疗程半年;依那普利组（对照组,５６例）：５￣１５ｍｇ／ｄ口服,疗程半年。治疗前后做动态血压监测,肝、肾功能,血糖等检查,测定血浆肾素活性（ＰＲＡ）、血管紧张素Ⅱ（ＡｎｇⅡ）、醛固酮、内皮素等。结果：治疗组降压总有效率为７２％（４１例）;降压幅度（ｋ     

Pharmacokinetics and depressor effect of delapril in patients with essential hypertension

The pharmacokinetics and depressor effect of a nonsulfhydryl angiotensin-converting enzyme inhibitor, delapril, was assessed by administering a single dose of 30 mg to nine patients with mild to moderate essential hypertension. Orally administered delapril is a prodrug and must be deesterified to its active metabolites, delapril diacid and 5-hydroxy delapril diacid. The pharmacokinetic parameters for delapril, delapril diacid, and 5-hydroxy delapril diacid were, respectively: t 1/2 0.30, 1.21, and 1.40 hours; Cmax 489, 635, and 229 ng/ml; AUC 572, 1859, and 948 ng X hr/ml. Delapril produced significant decreases in systolic blood pressure and angiotensin-converting enzyme activity 24 hours after dosing. There were no significant changes in the endogeneous creatinine clearance after the drug. Thus delapril may represent a useful antihypertensive agent for control of blood pressure in patients with essential hypertension.     

氯沙坦与氢氯噻嗪复方制剂治疗老年轻中度高血压的临床观察

目的 比较氯沙坦/氢氯噻嗪复方制剂与氯沙坦单剂治疗老年轻中度高血压的疗效与经济学评价.方法 分为导入期2周和治疗期8周.共入选99例轻中度原发性高血压患者,随机分为两组:复方制剂组50例,单剂组49例;分别给予氯沙坦50 mg/氢氯噻嗪12.5 mg复方片荆和氯沙坦50 mg 片剂每日1次治疗;治疗4周末时血压控制不满意者[坐位舒张压(SeDBP)≥85 mm Hg]随后4周分别增加氯沙坦50mg.结果 治疗2、4和8周后,复方制荆组与单剂组收缩压和舒张压均明显降低(均P<0.01);两组降压的总有效率相同,但是两组的显效率和有效率差异有统计学意义(均P<0.05).结论 复方制荆与单剂相比.能更快更显著降低收缩压和舒张压.对于需要两种或两种以上药物治疗的患者,复方制荆服药更方便,依从性更好,药物的效价比更好.     

Enalapril and lisinopril in the treatment of mild to moderate essential hypertension

Hypertensive patients were randomly assigned to receive 5 mg of enalapril (n = 50) or 10 mg of lisinopril (n = 47) daily. During a four-week titration period, the doses were increased weekly to a maximum of 40 mg once daily until the treatment goal of diastolic blood pressure (BP) of less than 90 mmHg was reached; treatment was then continued for four weeks. Systolic and diastolic BP declined significantly in the two treatment groups, from 147/98 mmHg in both the enalapril and lisinopril groups to 126/82 and 122/81 mmHg, respectively, at the end of treatment. During the first week of treatment, the goal of diastolic BP of less than 90 mmHg was reached by 40% of the enalapril group and 62% of the lisinopril group; by the end of the titration period, 98% and 96%, respectively, had achieved the BP goal. Few side effects were reported and there were no abnormal laboratory findings during treatment. It is concluded that once-daily administration of enalapril or lisinopril was generally effective and well-tolerated in the management of mild to moderate uncomplicated essential hypertension.     

联合药物治疗轻、中度原发性高血压降压效果和安全性的研究

目的 观察福辛普利联合小剂量氢氯噻嗪治疗轻、中度原发性高血压的降压效果和安全性.方法 轻、中度原发性高血压患者32例,服用福辛普利10 mg,qd,联用氢氯噻嗪25 mg,qd.疗程16周.定期门诊随访监测血压、心率,监测治疗前后血脂、血糖、电解质、肝肾功能等变化.结果 门诊随访2、4、8周的有效率分别为43%,71.5%,91.3%.在降低24小时平均收缩压(MSBP)、血压负荷以及24小时脉压(PP)方面均有明显效果,与治疗前相比差异有显著性意义(P<0.05).降压较平缓,治疗后动态血压曲线更趋于"杓形".谷峰比值(T/P)收缩压(SBP)和舒张压(DBP)分别为0.83和0.92,平滑指数(SI)SBP和DBP分别为3.01和2.97,治疗16周后,复查血液生化等指标与治疗前差异无显著性意义(P>0.05).结论 福辛普利联合小剂量氢氯噻嗪能持续平稳、有效及安全的降低24小时血压,且安全性良好.     

卡维地洛治疗轻、中度原发性高血压的临床疗效

目的 :观察卡维地洛治疗轻、中度原发性高血压的降压疗效。方法 :60例原发性高血压患者被随机分为卡维地洛组 (卡组 )和阿替洛尔组 (对照组 ) ,各 3 0例 ,分别给予卡维地洛 10～ 40mg/d和阿替洛尔 2 5～ 10 0mg/d ,疗程 8周。治疗前及治疗后 2、4、6、8周末测量坐位血压及心率 ,记录不良反应。结果 :( 1)治疗后两组病人的血压均有明显下降。卡组SBP/DBP降低 2 8.3 / 2 0 .1mmHg( 16.9%/ 19.5 %) ,对照组SBP/DBP降低 2 3 .5 / 16.9mmHg( 14 .3 %/ 16.5 %) ,分别与治疗前比较有显著性差异 (P <0 .0 1) ;两组间差异不显著 (P >0 .0 5 )。 ( 2 )卡组与对照组总有效率分别为 86.7%和 76.7%,总显效率分别为 66.7%和 60 .0 %,两组间差异不显著 (P >0 .0 5 )。 ( 3 ) 8周末 ,两组心率均降低 ,分别与治疗前比较有显著性差异 (P <0 .0 1) ,两组间差异不显著 (P >0 .0 5 )。结论 :卡维地洛治疗轻、中度高血压疗效确切、安全     

Efficacy and tolerability of enalapril and sustained-release verapamil in older patients with mild to moderate essential hypertension

The study involved 113 patients over age 50 years with mild to moderate essential hypertension, randomly assigned to treatment with enalapril (n = 54) or sustained-release verapamil (n = 59). During an eight-week titration period, doses were adjusted to achieve supine diastolic blood pressures (DBP) below 90 mmHg; patients were then given maintenance doses for eight weeks. Mean blood pressures were reduced significantly from 147.7/93.9 mmHg at baseline to 137.7/84.5 mmHg at the end of the maintenance period in the enalapril group and from 155.1/95.1 to 142.4/86.2 mmHg in the verapamil group. In the patients who completed treatment, the mean daily doses required to maintain DBP below 90 mmHg were 9.6 mg of enalapril and 244.9 mg of verapamil. There were 11 treatment failures in the enalapril group and 22 in the verapamil group: eight of the enalapril and 17 of the verapamil patients did not attain goal blood pressures and three and five were withdrawn because of side effects. It is concluded that both enalapril and sustained-release verapamil were generally effective and well tolerated in the treatment of mild to moderate hypertension in the middle-aged and older patients.     

运动、巯甲丙脯酸与巯甲丙脯酸运动肾显像检测原发性高血压的肾功能

目的：观察和分析运动（ＥＸ）、巯甲丙脯酸（ＣＡＰ）及巯甲丙脯酸运动（ＣＡＰ－ＥＸ）介入对轻中度原发性高血压（ＥＨ）患者肾功能的影响。方法：１０例正常志愿者和１５例轻中度原发性高血压患者,在１个月内完成基础双核素肾显像（ＢＳ－ＲＳ）、运动双核素肾显像（ＥＸ－ＲＳ）、巯甲丙脯酸双核素肾显像（ＣＡＰ－ＲＳ）及巯甲丙脯酸运动双核素肾显像（ＣＡＰ－ＥＸ－ＲＳ）４次检查。图像均按ＡＤＡＣ公司提供的计算机软件进行处理。结果：ＥＸ和ＣＡＰ－ＥＸ介入,ＧＦＲ,ＥＲＰＦ均明显降低（Ｐ＜００１）;而ＣＡＰ介入未见明显变化。ＥＨ组与对照组相应方法间ＧＦＲ,ＥＲＰＦ不存在显著差异（Ｐ＞００５）。１５例ＥＨ患者中,基础肾显像及巯甲丙脯酸肾显像结果均正常,而４０％（６／１５）的患者出现异常运动肾图,３０％（５／１５）出现异常巯甲丙脯酸运动肾图,二者同时异常的有５例,其中１例于ＣＡＰ－ＥＸ－ＲＳ介入时,异常更加明显,均表现为对称性的１３１Ｉ－ＯＩＨ和９９ｍＴｃ－ＤＴＰＡ排泄延迟,１３１Ｉ－ＯＩＨ肾图和９９ｍＴｃ－ＤＴＰＡ肾图曲线宽大,排泄段抬高。上述异常变化在１３１Ｉ－ＯＩＨ和９９ｍＴｃ－ＤＴＰＡ肾图曲线中,以９９ｍＴｃ－ＤＴＰＡ肾图     

Quinapril versus atenolol in the treatment of mild to moderate essential hypertension.

A randomized, double-blind, parallel-group study was conducted to compare the safety and efficacy of the angiotensin-converting enzyme inhibitor quinapril with that of the beta-blocker atenolol. Fifty-six outpatients with mild to moderate hypertension were enrolled in the trial. After a 4-week washout period, 27 patients were treated with quinapril 20 mg once daily and 29 patients were treated with atenolol 50 mg once daily for 4 weeks. During a third 4-week period, the daily doses were adjusted on an individual basis. At the end of the 8-week treatment period, the systolic and diastolic blood pressures were significantly reduced in both groups of patients. Heart rate was significantly reduced only in the atenolol group. Adverse effects were inconsequential and comparable in both groups. Quinapril was shown to be a safe and effective treatment for patients with mild to moderate hypertension.     

Effects of pindolol on serum lipids, apolipoproteins, and lipoproteins in patients with mild to moderate essential hypertension

The effects of 12 weeks' administration of the beta-blocker pindolol (5 mg twice daily) on serum lipids, apolipoproteins (apo), and lipoproteins were studied in 20 normolipidemic patients with mild to moderate essential hypertension (WHO I-II). Pindolol significantly increased both high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), while very-low-density lipoprotein cholesterol (VLDL-C) was significantly decreased. Apo A-II levels were increased significantly and the apo B/apo A-I ratio, which is one of the atherogenic indexes, was decreased significantly after pindolol therapy. Total cholesterol, HDL subfraction cholesterols, the LDL-C/HDL-C ratio, triglycerides, apo A-I, apo B, apo C-II, apo C-III, and apo E did not change significantly.     

Ramipril and methyldopa compared in patients with mild to moderate hypertension

Twenty-seven patients with mild to moderate essential hypertension were randomly assigned to receive 5 mg of ramipril once daily or 250 mg of methyldopa twice daily for eight weeks. Similar reductions in diastolic blood pressure and heart rate were noted in the two treatment groups during treatment. Perhaps because of the limited number of patients, no between-group differences in the results of a measure of quality of life were found, but on overall assessments of treatment outcome by patients and the investigator, slightly better outcome was apparent in the ramipril-treated patients. No side effects or clinically significant changes in laboratory test results were reported. It is concluded that ramipril is a safe and effective agent in mild to moderate hypertension when administered as a single daily dose.     

Antihypertensive efficacy of amlodipine and losartan after two 'missed' doses in patients with mild to moderate essential hypertension

We compared the effects of amlodipine (5-10 mg, n=94) and losartan (50-100 mg, n=94) on the lowering of blood pressure (BP) at steady state and after two missed doses, as well as on tolerability. This was a randomized, double-blind study of 12 weeks of active treatment followed by 2 days of placebo treatment. Twenty-four-hour ambulatory blood pressure monitoring and office BP measurements were performed at baseline, week 12 and after the 2-day drug holiday. After 12 weeks, amlodipine was significantly more effective than losartan in reducing both 24-h systolic blood pressure (SBP) (-18.0 versus -10.8 mmHg) and diastolic blood pressure (DBP) (-10.6 versus -8.0 mmHg). While mean SBP and DBP for both treatments increased comparably during the drug holiday, BP values remained significantly lower than baseline for both treatments. The superior BP-lowering effect of amlodipine compared with losartan was maintained during the drug holiday.     

The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study

Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.