Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study*

ABSTRACT

Objectives: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combInation antihypertensiVe thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy.

Research design and methods: Patients remaining hypertensive (systolic BP [SBP], 145–180?mmHg; diastolic BP [DBP], 95–105?mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), β-blocker (n = 629), calcium-channel blocker (CCB; n = 493), angiotensin II type 1 receptor blocker (ARB; n = 75), α-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5?mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded.

Main outcome measures and results: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 ± 16?mmHg at baseline vs. 132 ± 12?mmHg at 3 months; DBP, 102 ± 8?mmHg vs. 83 ± 6?mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, β-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 ± 15/19 ± 9, 33 ± 17/19 ± 10, 33 ± 15/18 ± 8 or 35 ± 16/20 ± 12?mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (≤?140?mmHg) and 61% achieved BP normalisation (SBP <?140, DBP <?90?mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity.

Conclusions: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other antihypertensive agents.     

The efficacy of indapamide in hypertensive patients failing to respond to a beta-blocker alone

A double-blind, placebo-controlled, cross-over study was carried out to evaluate the efficacy and safety of 2.5 mg indapamide in 24 hypertensive patients failing to respond to oxprenolol alone. An additional 6 patients were assessed by ambulatory blood pressure recordings over a 15-hour period with a Remler M2,000 semi-automatic sphygmomanometer. On average, indapamide reduced supine blood pressure by 18.5/10 mmHg and standing blood pressure by 19.6/8.9 mmHg. The ambulatory recordings carried out in 6 patients detected a fall in diastolic pressure not observed using clinic readings in these 6 patients, suggesting that this is a more sensitive method of detecting antihypertensive effect. These responses were not associated with significant changes in heart rate or body weight and there was no significant postural fall in blood pressure. No serious side-effects were reported. Changes in serum potassium, chloride and urate similar to those seen with diuretics were observed. These results suggest that indapamide is a useful and safe adjunct to beta-adrenoceptor blocking therapy for uncontrolled hypertension.     

Once daily indapamide in the treatment of the elderly and young hypertensive

Summary Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.     

硝苯地平缓释剂联合利尿剂治疗173例老年高血压患者安全性与有效性临床观察

目的探讨硝苯地平缓释剂联合不同利尿剂(氢氯噻嗪和吲达帕胺)的治疗方案对老年高血压患者的降压安全性及有效性,以寻找适合我国老年高血压患者的降压方案。方法将173例老年高血压患者随机分为3组,Nif组服硝苯地平缓释片10 mg/次,2次?d-1;Nif+HCTZ组在服用硝苯地平基础上加服氢氯噻嗪,剂量为12.5 mg/次,1次?d-1,Nif+ID组在服用硝苯地平基础上加服吲达帕胺,剂量为2.5 mg/次,1次?d-1,疗程8周,考察用药期间血压的变化,进而评价3种用药方案的有效率及安全性。结果 Nif组平均坐位血压从(172.4±12.3)/(101.4±8.6)mmHg降为(150.9±11.6)/(86.4±7.1)mmHg;Nif+HCTZ组平均坐位血压从(176.7±13.6)/(100.8±7.65)mmHg降为(139.7±12.7)/(81.3±8.2)mmHg;Nif+ID组平均坐位血压从(175.4±11.8)/(105.2±9.03)mmHg降为(142.5±10.8)/(81.6±8.6)mmHg。2种联合用药方案有效率与Nif组降压有效率相比,差异有统计学意义(P<0.01),对血钾和肾功能影响差异无统计学意义。主要不良反应为颜面潮红和踝部水肿,Nif+HCTZ组及Nif+ID组比Nif组老年患者不良反应明显减少。结论硝苯地平缓释剂联合利尿剂氢氯噻嗪或吲达帕胺,降压有效率高于单用硝苯地平缓释剂,对老年高血压患者代谢无影响,是老年高血压的有效治疗方案。     

Evaluation of high dose of perindopril/indapamide fixed combination in reducing blood pressure and improving end-organ protection in hypertensive patients

ABSTRACT

Background: Despite the widespread notion that controlling hypertension is essential to improve cardiovascular outcome, uncontrolled hypertension rates remain high. Fixed-dose combinations are used routinely to reduce the impact of hypertension. Treatment with fixed-combination perindopril/indapamide, for example, at the currently approved doses (perindopril 2?mg/indapamide 0.625?mg [Per2/Ind0.625] and perindopril 4?mg/indapamide 1.25?mg [Per4/Ind1.25]), reduces blood pressure, end-organ damage, and cardiovascular morbidity and mortality in a wide range of hypertensive patients.

Aim and scope: This article reviews three published randomised trials that evaluated the efficacy and safety of the highest dose of perindopril/indapamide (perindopril 8?mg/indapamide 2.5?mg [Per8/Ind2.5]) in blood pressure lowering and end-organ protection studies.

Results: In the first (dose-finding) study, incremental reductions in SBP/DBP were observed with each dose doubling. After 8 weeks of treatment, decreases in supine SBP/DBP were statistically significant compared to placebo for all three doses, with incremental and progressive reductions with each dose doubling: ranging from SBP/DBP respectively ?14/?9?mmHg for Per2/Ind0.625 to ?23/?15?mmHg for Per8/Ind2.5 compared to ?5/?5?mmHg for placebo. In the PICXEL and PREMIER trials, SBP/DBP decreases of 16.3/8.1?mmHg (p?<?0.0001) and 2.5/2.6?mmHg, respectively, were noted when Per4/Ind1.25 was doubled to Per8/Ind2.5 (decreases from 167.7/101.7 to 151.4/93.6 in PICXEL and from 154.9/92.1 to 152.4/89.5 in PREMIER, respectively). As a consequence more patients had normalised blood pressure (22% and 17%), more patients responded to treatment (68% and 45%), and 29% and 10% of non-responders became responders, in PICXEL and PREMIER, respectively. Additional end-organ benefits were also noted with Per8/Ind2.5. In PICXEL, significant decreases from baseline in left ventricular mass were noted with all three doses, with a 17.5?g/m² decrease from baseline in patients whose maximum dose was Per8/Ind2.5 (from 148.5?g/m²?±?39.5 (mean?±?SD) to 131?g/m²; p?<?0.0001). In PREMIER, changes in albumin excretion rate were also noted with all three doses, with a 45% reduction from baseline in patients whose maximum dose was Per8/Ind2.5 (p?<?0.0001). When safety data, including potassium levels, were analysed, the increase in dose to Per8/Ind2.5 did not have a notable impact on the safety profile of perindopril/indapamide.

Conclusions: Based on data available from an evaluation of three randomised clinical trials, fixed-combination Per8/Ind2.5 provided a significant, incremental reduction in blood pressure as well as cardiac and renal end-organ protection while remaining safe and well-tolerated.     

吲达帕胺对中老年高血压患者糖脂尿酸代谢及电解质的影响

目的探讨吲达帕胺对无糖脂代谢紊乱的中老年高血压患者糖脂尿酸代谢及电解质的影响。方法将无糖脂代谢紊乱的中老年高血压患者,停服原降压药物2周后,随机分成2组：硝苯地平控释片组（拜新同30rag／d）和吲达帕胺组（寿比山2．5mg／d）,连续服药12周,观察血压控制平稳患者血糖、血脂、尿酸、电解质的变化。结果吲达帕胺组经治疗后仅血压、血尿酸、血钾较治疗前有显著差异（P〈0．05）,其余及拜新同组各项生化指标均无显著差异（P〉0．05）。结论小剂量吲达帕胺在治疗无代谢紊乱的中老年高血压患者中,无明显糖脂代谢影响,但长期服用后,可能会导致低钾血症和高尿酸血症,故需定期检测血钾和血尿酸,减少和避免不良反应的发生。     

氯沙坦与吲达帕胺在老年中重度高血压治疗中的比较

目的比较氯沙坦与吲达帕胺治疗老年中重度原发性高血压的疗效及安全性。方法氯沙坦组和吲达帕胺组各106例,在硝苯地平控释片基础上分别加用氯沙坦及吲达帕胺,治疗8周,观察治疗前后血压变化及血钾、尿酸变化。结果两组血压每周末与治疗前相比有显著性差异(P<0.05),吲达帕胺组血钾、氯沙坦组及吲达帕胺组血尿酸治疗后较治疗前均有显著性差异(P<0.05),两组间治疗后血尿酸有显著性差异(P<0.01)。结论氯沙坦与吲达帕胺治疗老年中重度原发性高血压均有效,氯沙坦治疗安全可靠,而吲达帕胺治疗降低血钾及升高血尿酸使其在临床应用受到一定的限制。     

培哚普利/吲哒帕胺复合制剂治疗高血压患者的多中心、随机、双盲对照研究

目的：比较低剂量培哚普利／吲哒帕胺复合制剂与吲哒帕胺缓释剂治疗高血压患者血压的变化和治疗反应率及其安全性。方法：共入选原发性高血压病患者231例。经2周安慰剂洗脱期后，分为试验组（n=116）和对照组（n=115）。完成试验患者210例，符合方案分析集（PPS）203例，其中试验组107例，对照组96例。2组随机双盲接受培哚普利2ms／吲哒帕胺0．625mg或吲哒帕胺缓释剂（纳催离SR）1．5mg，qd；治疗6周后，如果舒张压（DBP）〈90mmHg，继续上述治疗；如果DBP≥90mmHg，试验组改为qid口服培哚普利4mg／吲哒帕胺1．25mg；对照组在纳催离SR的基础上加用美托洛尔50mg，qd，继续治疗6周。部分患者在治疗前及治疗12周时行动态血压检测（ABPM）。结果：用药后第6周时，试验组药物剂量加倍比率为48．6％（52／107），对照组有54．2％（52／96）的病例需加用美托洛尔，两组加药率比较无差异（P=0．43）。与给药前比较，治疗12周后两组DBP均明显下降（P〈0．01），下降幅度试验组和对照组平均为12．4和13．6mmHg（P=0．191），两组收缩压（SBP）在用药后各时点亦均明显下降（P〈0．01），下降幅度为15．4和15．7mmHg。两组ABPM各指标均明显下降，试验组和对照组的DBP各峰比（T／P）为80％和47％。两组不良事件发生率无差异，主要的不良事件为咳嗽、鼻炎、低钾血症。结论：2种治疗方法12周后均可显著降低DBP和SBP。试验组可以维持24h平稳降压。两组不良反应发生率相似。     

盐酸戊乙奎醚用于老年患者术前用药的疗效评价

目的评价盐酸戊乙奎醚用于老年患者术前用药的临床疗效。方法将70例择期手术的老年患者,按随机数字表法分成观察组和对照组。对照组术前用药为硫酸阿托品0.01mg/kg肌内注射;观察组术前用药为盐酸戊乙奎醚0.01mg/kg肌内注射。结果注药5、15、30min后,两组口干程度明显高于注药前,差异有统计学意义（P〈0.05）。注药5、15、30min后,观察组心率变化小于对照组,差异有统计学意义（P〈0.01）。结论盐酸戊乙奎醚用于老年患者术前用药疗效可靠,抑制腺体分泌作用明显,血流动力学稳定,是一种理想的老年患者术前用药。     

The efficacy and tolerance of indapamide in essential hypertension: a multi-centre study in 981 patients

A multi-centre open trial involving 150 cardiologists throughout France was undertaken to assess the efficacy and tolerance of indapamide in the treatment of essential hypertension. An identical protocol was used by all of the cardiologists. A total of 981 patients (mean age 58 years) was included in the trial after an observation period of 1 month during which blood pressure was recorded regularly. Patients were included if they had permanent essential hypertension with a diastolic pressure of 95 mmHg or more. Mean systolic and diastolic blood pressures at the end of the initial observation period were 179/103 mmHg. The treatment period lasted for 4 months during which the patients received 1 tablet of indapamide (2.5 mg) each morning. Blood pressure was measured after 6 and 16 weeks of treatment, and clinical and biological acceptability was also assessed. After 6 weeks of treatment, mean systolic and diastolic blood pressure levels decreased to 158/90 mmHg: after 16 weeks these mean figures were 150/86 mmHg. Blood pressure levels became normal with indapamide treatment alone in 80% of patients. A slight decrease in serum potassium levels was noted in the first 6 weeks of treatment and then became stable. Clinical acceptability was considered good or excellent in 89% of cases and few non-specific side-effects were reported.     

The efficacy and tolerance of indapamide in essential hypertension: a multi-centre study in 981 patients

Summary

A multi-centre open trial involving 150 cardiologists throughout France was undertaken to assess the efficacy and tolerance of indapamide in the treatment of essential hypertension. An identical protocol was used by all of the cardiologists. A total of 981 patients (mean age 58 years) was included in the trial after an observation period of 1 month during which blood pressure was recorded regularly. Patients were included if they had permanent essential hypertension with a diastolic pressure of 95 mmHg or more. Mean systolic and diastolic blood pressures at the end of the initial observation period were 179/103 mmHg. The treatment period lasted for 4 months during which the patients received 1 tablet of indapamide (2.5?mg) each morning. Blood pressure was measured after 6 and 16 weeks of treatment, and clinical and biological acceptability was also assessed. After 6 weeks of treatment, mean systolic and diastolic blood pressure levels decreased to 158/90 mmHg: after 16 weeks these mean figures were 150/86 mmHg. Blood pressure levels became normal with indapamide treatment alone in 80% of patients. A slight decrease in serum potassium levels was noted in the first 6 weeks of treatment and then became stable. Clinical acceptability was considered good or excellent in 89% of cases and few non-specific side-effects were reported.     

经皮冠状动脉腔内成形术治疗老年冠心病的近期和远期疗效观察

目的　探讨经皮冠状动脉腔内成形术 (PTCA)和支架术治疗老年冠心病患者的近期和远期疗效。方法　连续 2 5 0例冠心病患者 32 1处病变行 PTCA治疗 ,依年龄分为 >6 5岁组 (10 2例 )和≤ 6 5岁组 (14 8例 )。观察手术成功率和住院期并发症。术后每 3～ 4个月定期临床随访 ,如有心肌缺血可疑表现 ,则重复冠脉造影检查 ,如发现再狭窄≥ 70 %则再次进行介入治疗 ,记录再次靶血管重建 (TL R)、总心脏事件和无心脏事件存活率。结果　与≤6 5岁组相比 ,>6 5岁组的女性、糖尿病、高血压病、三支血管病变较多见。两组手术成功率相似 ,分别为 91.2 %和92 .1% (P>0 .0 5 )。随访 6个月两组患者再次靶血管重建 (TL R)、总心脏事件和无心脏事件存活率均相似。结论　经皮冠状动脉腔内成形术 (PTCA)和支架术治疗老年冠心病患者的近期疗效和远期预后良好 ,与年龄无明显关系。     

托伐普坦在心衰合并低钠血症老年患者中的疗效评价

目的评价托伐普坦治疗老年心衰合并低钠血症患者的临床疗效。方法选取2014年9月至2016年6月在我院心内科住院的老年心衰合并低钠血症患者(年龄≥60岁)46例,采用随机数字表法将患者分为托伐普坦组(托伐普坦+常规治疗)和呋塞米组(呋塞米+常规治疗),每组23例,比较两组患者治疗前及治疗后第7天的血钠、脑钠肽(BNP)、尿量、体重、左心室射血分数(LVEF)、生活质量评分情况,同时分析两组用药期间不良反应发生率、住院时间、出院后180 d心血管死亡情况。结果托伐普坦组治疗后第7天较治疗前血清钠、尿量、LVEF升高,BNP、体重、生活质量评分下降(P<0.05)。呋塞米组治疗后第7天较治疗前尿量升高,体重、BNP、生活质量评分降低(P<0.05)。治疗后第7天托伐普坦组较呋塞米组血清钠、尿量、LVEF升高,BNP、体重、生活质量评分降低(P<0.05)。托伐普坦组较呋塞米组住院时间缩短,口干、口渴发生率升高(P<0.05)。两组患者出院后180 d心血管死亡率比较差异无统计学意义(P>0.05)。结论托伐普坦可以显著增加老年心衰合并低钠血症患者的血清钠水平,强效利尿,提高心脏功能,改善短期生活质量,对180 d预后无影响。     

吲达帕胺致高血压患者三酰甘油水平升高

1例46岁男性患者因高血压自行口服氯沙坦钾50 mg,1次/d。7个月后,因血压控制不理想加服吲达帕胺2.5 mg,1次/d。又5个月后,三酰甘油(TG)由1.18 mmol/L升至5.07 mmol/L。患者控制饮食并坚持适量运动。2个月后,TG水平为4.75 mmol/L。考虑为吲达帕胺致TG水平异常。停用吲达帕胺,15 d后TG降至0.89 mmol/L。     

Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients

Recent studies showed that in diabetic hypertensive patients, administration of angiotensin-converting enzyme (ACE)-inhibitors or calcium antagonists can effectively lower blood pressure (BP) and prevent diabetes-related cardiovascular complications with no adverse metabolic effects. We sought to assess the antihypertensive and metabolic effects of the new dihydropyridine calcium antagonist manidipine (M) in patients with diabetes mellitus and essential hypertension as compared with the ACE inhibitor enalapril (E). After 3 weeks of placebo, 101 (62 men; age range, 34-72 years) hypertensives with type II diabetes mellitus were randomized to M 10-20 mg or E 10-20 mg, od, for 24 weeks. At the end of the placebo period and the active-treatment phase, BP was measured with a mercury sphygmomanometer (office, O) and over the 24 h by ambulatory (A) monitoring. ABP recordings were analyzed to obtain 24-h, day (6 a.m. to midnight), and night (midnight to 6 a.m.) average systolic (S) and diastolic (D) BP and heart rate (HR) values. Homogeneity of the antihypertensive effect over the 24 h was assessed by the smoothness index [SI: i.e., the ratio between the average of the 24 hourly BP changes after treatment and the corresponding standard deviation (the higher the SI, the more uniform is the BP control by treatment over the 24 h]. The O SBP and DBP were significantly (p < 0.01) and similarly reduced by M (16 +/- 10 and 13 +/- 6 mm Hg, n = 49) and E (15 +/- 10 and 13 +/- 6 mm Hg, n = 45). The percentage of patients whose O DBP was reduced < or = 85 mm Hg (i.e., the value indicated to be the optimal DBP goal in diabetic hypertensives) was similar for M (37%) and E (40%). The reduction of 24-h BP also was similar between M (n = 38) and E (n = 38) for both drugs (systolic, 6 +/- 11 and 8 +/- 10 mm Hg; diastolic, 5 +/- 8 and 5 +/- 7; NS, M vs. E). The antihypertensive effect was distributed in a similar homogeneous fashion throughout the dosing interval, as shown by the similar SI values (M, 0.6 +/- 1.2 for SBP and 0.6 +/- 0.9 for DBP; E, 0.6 +/- 0.8 for SBP and 0.5 +/- 0.7 for DBP; NS, M vs. E). O and A HR were unchanged by either treatment. Markers of glucose and lipid metabolism and renal function were not significantly modified by treatment both with M and with E. In the diabetic hypertensives, M was as effective and metabolically neutral as the ACE-inhibitor E.     

伊拉地平缓释胶囊对高血压的疗效

伊拉地平（ｉｓｒａｄｉｐｉｎｅ）缓释胶囊５－１０ｍｇｑｄｐｏ连续６ｗｋ治疗原发性高血压３０例，男性１７例、女性１３例，年龄５０±ｓ８ａ，发现对轻、中型高血压有效率达９０％，治疗后收缩压下降１２％，舒张压下降１５％。除轻微头痛、头晕外，无心动过速及其他严重不良反应。伊拉地平缓释胶囊降压效果良好，作用持久平稳，服用方便，不良反应小，有较大应用前景。     

老年高血压患者社会支持状况调查

目的调查本地区老年高血压患者社会支持状况,为防治高血压提供参考。方法 2009年6月～2011年10月在本科住院的高血压患者200例中,年龄30～59岁100例（中青年组）,60～83岁100例（老年组）。对两组患者进行社会支持评定量表（SSRS）调查。结果中青年组高血压患者社会支持及其3个维度得分均高于老年组,两组比较均差异有统计学意义（P〈0.05）。结论本地区老年高血压患者的社会支持情况普遍不好,应加强社会支持力度,提高支持利用度。     

对老年高血压合并糖尿病患者采取社区规范性管理的效果评价

目的研究深圳市社区健康管理对于高血压、2型糖尿病等慢性疾病的干预效果。方法选择我中心高血压和2型糖尿病100例患者随机分为干预组和对照组,对照组进行常规管理,干预组采用社区健康管理,比较干预后两组患者的干预效果。结果实施健康管理前,两组患者血糖、血压等指标比较不存在明显差异,实施健康管理后干预组患者血糖、血压等指标优于对照组患者(P<0.05),研究组患者干预后负性情绪、生活质量评分均显著高于对照组,两组间差异有统计学意义(P<0.05)。结论对深圳市社区中患高血压和2型糖尿病的慢性疾病患者进行健康管理,有利于降低患者的血压水平、血糖水平,提高患者生活质量。     

Pharmacokinetics and hemodynamic effects of long-term nisoldipine treatment in hypertensive patients

In six patients with essential hypertension, the pharmacokinetics of nisoldipine were investigated before, during, and after 4 weeks of treatment. On day 1, nisoldipine was infused intravenously (i.v. 2 mg in 2 h); on day 2, oral nisoldipine treatment (10-mg tablets twice daily) was started for 4 weeks. During this period, patients came to the hospital six times, on which occasions blood samples were taken for the determination of trough and peak concentrations of nisoldipine. After 4-week treatment, the infusion experiment was repeated. In the first infusion experiment, systemic clearance was 1.02 +/- 0.23 L/min (mean +/- SD), terminal half-life (t1/2) was 15.4 +/- 6.7 h, and volume of distribution was 5.9 +/- 1.8 L/kg. After 4 weeks, these parameters had not changed significantly. Nisoldipine lowered blood pressure (BP) in all patients, whereas forearm blood flow and heart rate (HR) increased. Neither were the hemodynamic changes different after the oral treatment period, although basal BP was lower than before oral treatment. No accumulation of nisoldipine occurred during the 4-weeks treatment period.