Quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension

This 8-week, double-blind, multicentre study compared the efficacyand safety of the combination of quinapril and hydrochlorothiazide(HCTZ) with each drug as monotherapy. Outpatients with moderateto severe hypertension defined as supine diastolic blood pressure(DBF) 105 mmHg and 120 mmHg at the end of a 2 to 4-week placebo-baselineperiod were randomly assigned to one of the three treatments:once-daily 10 mg quinapril plus 12.5 mg HCTZ or monotherapywith these doses. After 4 weeks, the doses were to be doubledfor the remaining 4 weeks. Three hundred and sixty-eight patientswere randomized to double-blind medication; 346 completed thestudy. Seven patients withdrew due to lack of efficacy. Fourpatients withdrew due to side effects. In all three treatmentgroups, clinically significant reductions in DBP were achieved.Combination therapy was statistically more effective than eachcomponent taken as monotherapy. Adverse events were infrequentin all treatment groups. No patients experienced symptomatichypotension or orthostatic hypotension.     

Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to ramipril monotherapy.

In a parallel-group multicenter study, the efficacy and safety of combination therapy with ramipril 5 mg plus hydrochlorothiazide 25 mg were compared double-blind with those of 5 mg and 10 mg ramipril monotherapy in patients with mild to moderate hypertension who had not responded adequately to ramipril 5 mg alone. Patients were initially treated single-blind for 1 week with ramipril 2.5 mg and 3 weeks with ramipril 5 mg. Of 240 patients enrolled, 165 were subsequently classed as nonresponders (diastolic blood pressure > 90 mmHg) and were randomized to one of the three double-blind treatments for a further 4 weeks. In the double-blind phase, the mean reductions in supine systolic and diastolic blood pressures at end point were significantly greater in the 5 mg plus 25 mg combination group (11.6/10.6 mmHg) than in the groups receiving ramipril 5 mg (6.2/5.9 mmHg; both p < 0.01) and ramipril 10 mg (7.4/7.1 mmHg; both p < 0.05). The proportion of responders at end point was also higher for combination therapy (72%) than for monotherapy (48% for ramipril 5 mg and 62% for ramipril 10 mg). All three treatments were well tolerated. Analysis of laboratory values revealed no clinically important changes.     

Double-blind comparison of amlodipine and hydrochlorothiazide in patients with mild to moderate hypertension

In the final analysis of this study at Week 26,26% of the patients randomized to receive amlodipine attained blood pressure control with amlodipine alone compared with 33% of the patients allocated to hydrochlorothiazide (HCTZ). Neither amlodipine nor HCTZ produced clinically significant changes in pulse rate or in the electrocardiogram. Amlodipine treatment did not appear to produce clinically significant changes in blood lipids; HCTZ, however, produced an increase in total plasma cholesterol (Δ22.9 ± 8.6 mg/dl). The incidence of side effects and the rate of patient withdrawal in the amlodipine and HCTZ groups were comparable. As expected, HCTZ therapy caused well-recognized biochemical alterations in cholesterol and potassium levels, whereas amlodipine was metabolically neutral.     

Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension—part 2: An open long-term study of efficacy and safety

In an open, multicenter extension of a short-term study, 159 patients with mild to moderate hypertension were treated with either ramipril monotherapy or a combination of ramipril and hydrochlorothiazide for up to 1 year. Patients started with either 5 mg ramipril once daily (responders in the short-term study) or a combination of ramipril 5 mg plus hydrochlorothiazide 25 mg once daily. The dose could be adjusted and nonresponders to ramipril monotherapy could have hydrochlorothiazide added. In the 38 patients treated with ramipril monotherapy, the largest drop in mean blood pressure (BP) had already occurred in the previous short-term study; from Week 2 in the long-term study, the BP remained stable with means below 150/90 mmHg. In the 83 patients treated with the combination for 50 weeks or more, mean BP continued to decrease until around Week 10 in the long-term study while therapy was being adjusted. Thereafter, it also remained stable with means below 150/85 mmHg. Both treatment groups showed good mean reductions at end point, as did the group of 38 patients treated with the combination for less than 50 weeks. High response rates (84–95%) were seen in all groups at end point. The combination was well tolerated and the efficacy of ramipril in combination with hydrochlorothiazide was maintained over the 1-year period of investigation.     

A comparative study on the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension

Purpose: Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL).

Method: Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50?mg/day)/HCTZ (12.5?mg/day) (LOS?+?HCTZ group: n?=?37) or telmisartan (40?mg/day)/HCTZ (12.5?mg/day) (TEL?+?HCTZ group: n?=?22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated.

Results: Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS?+?HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL?+?HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS?+?HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4?mg/dl, while LOS?+?HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5?mg/dl. TEL?+?HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4?mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4?mg/dl, TEL?+?HCTZ increased HOMA-R, whereas LOS?+?HCTZ did not.

Conclusions: LOS?+?HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL?+?HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.     

厄贝沙坦氢氯噻嗪复方片治疗轻中度高血压疗效观察

目的探讨厄贝沙坦氢氯噻嗪复方片治疗轻中度高血压的临床疗效。方法分析2008年1月至2013年1月我院收治的180例轻中度高血压患者的临床资料,将患者分为2组,比较2组患者的疗效差异。结果对照组患者经厄贝沙坦治疗,降压总有效率为68．89％,治疗组患者经厄贝沙坦氢氯噻嗪片治疗,降压总有效率为87．78％,明显高于对照组,经比较,P〈0．05,差异具有统计学意义。结论厄贝沙坦氢氯噻嗪复方片治疗轻中度高血压疗效确切,值得推广使用。     

厄贝沙坦/氢氯噻嗪复方片治疗老年轻中度原发性高血压96例临床观察

目的评价老年高血压患者接受厄贝沙坦/氢氯噻嗪复方制剂(商品名安博诺)治疗的有效性及安全性。方法96例老年轻中度高血压病患者,随机分为厄贝沙坦组:厄贝沙坦150mg,1～2次/d;厄贝沙坦/氢氯噻嗪复方片组48例,厄贝沙坦150mg/氢氯噻嗪12.5mg,1次/d,均口服,治疗8周。治疗前后监测血糖、血尿酸、肌酐、血脂和血钾。结果两组治疗前后代谢无明显改变,厄贝沙坦组降压总有效率70.8%,复方片组总有效率89.6%,P<0.05。结论厄贝沙坦/氢氯噻嗪复方片剂治疗老年高血压安全有效,不良反应少。     

氯沙坦与吲达帕胺或氢氯噻嗪合用的降压疗效观察

目的 :研究和评价氯沙坦与吲达帕胺或氢氯噻嗪合用降压疗效及对代谢的影响。方法 :选择 45例轻—中度原发性高血压患者 ,随机分成 3组 ,每组各 15例。氯沙坦组 :单用氯沙坦 5 0～ 10 0mg ,每日一次 ;氯沙坦与吲达帕胺合用组 :氯沙坦 5 0mg ,每日一次 ,加吲达帕胺 2 .5mg ,每日一次 ;氯沙坦与氢氯噻嗪合用组 :氯沙坦 5 0mg ,每日一次 ,加氢氯噻嗪 12 .5mg ,每日二次。三组疗程均为 12周。观察三组治疗前后的随测血压 (CBP)和 2 4小时动态血压 (ABPM)及生化指标。结果 :氯沙坦加吲达帕胺或加氢氯噻嗪组降压总有效率及随测血压、2 4小时动态血压的变化均明显优于氯沙坦单用组 ,且治疗前后心率和生化指标无明显改变。结论 :氯沙坦与吲达帕胺或氢氯噻嗪联合应用降压效果较单用氯沙坦更有效 ,且对代谢无影响     

Comparison of fosinopril and hydrochlorothiazide in patients with mild to moderate hypertension.

Seventeen patients with mild to moderate hypertension, as indicated by a diastolic blood pressure (DPB) of 95-115 mmHg (WHO I), were treated in a randomized, double-blind, parallel study, with either 5 mg of fosinopril, a new phosphinic acid-containing angiotensin converting enzyme (ACE) inhibitor, or 25 mg of hydrochlorothiazide administered orally once daily for 4 weeks after a 4- to 6-week run-in period of placebo. The doses were increased to 10 mg of fosinopril or 50 mg of hydrochlorothiazide if DBP remained above 95 mmHg. The blood pressure (BP) fell from 157 +/- 12/104 +/- 7 mmHg (mean value +/- SD) at the start of the study to 146 +/- 21/97 +/- 8 mmHg (P less than 0.02) after 4 weeks, and to 149 +/- 19/97 +/- 7 mmHg (P less than 0.02) after 8 weeks of fosinopril treatment (n = 8). In the hydrochlorothiazide-treated patients (n = 9), BP fell from 153 +/- 9/105 +/- 5 mmHg at the start of the study to 140 +/- 11/97 +/- 7 mmHg (P less than 0.01) after 4 weeks, and to 131 +/- 11/94 +/- 7 mmHg (P less than 0.01) after 8 weeks. After the first dose, DBP fell from 102 to 99 mmHg (NS) in fosinopril-treated patients, and from 105 to 96 mmHg (P less than 0.02) in hydrochlorothiazide-treated subjects. Serum active fosinoprilate concentration increased to 5.6 ng ml-1, 25.9 ng ml-1, and 43.8 ng ml-1 after 30, 60 and 120 min, respectively, and remained at a level of 6.6-7.7 ng ml-1 after 4 and 8 weeks, respectively. Serum ACE activity decreased from 21.6 +/- 11.0 mumol min-1 l-1 at the start to 9.3 +/- 13.7, 4.4 +/- 4.6, and 2.9 +/- 2.8 mumol min-1 l-1 after 30, 60 and 120 min, respectively. No side-effects and no changes in blood counts, electrolytes or kidney function were attributed to fosinopril during the study. Fosinopril is a safe, long-acting antihypertensive drug with a smooth onset of action. Hydrochlorothiazide treatment caused potassium loss and an increase in the levels of uric acid and triglycerides. Diastolic blood pressure decreased to the same extent as a result of treatment with either drug, while systolic blood pressure was better controlled by hydrochlorothiazide.     

氯沙坦治疗轻、中度高血压病疗效的评价

目的 :评价氯沙坦治疗轻、中度高血压病患者的疗效。方法 :采用随机双盲试验 ,将轻、中度高血压病 （EH）患者随机分为氯沙坦组 （36例 ）和依那普利组 （34例 ） ,分别服用氯沙坦 5 0 m g/d和依那普利 10 m g/d,共 8周。治疗 4周后 ,对舒张压 （DBP）≥ 90 m m Hg的患者 ,剂量加倍。于服安慰剂期末和治疗 4,8周末观察 DBP和收缩压 （SBP）及心率 （HR）、干咳发生率及临床实验室检查。结果 :8周末 ,氯沙坦组有效率为 72 % ,依那普利组为 74% ,两组间无显著差异 （P>0 .0 5 ）。两组平均 DBP和 SBP均有显著下降 ,两组间血压降幅无显著差异 （P>0 .0 5 ）。干咳发生率氯沙坦组 （3% ）明显低于依那普利组 （18% ,P<0 .0 1）。结论 :氯沙坦 5 0～ 10 0 m g/d治疗轻、中度高血压病疗效确切 ,干咳发生率低。     

A clinical trial evaluating the 24-hour effects of bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination in patients with mild to moderate hypertension

This study used 24-h ambulatory blood pressure (BP) monitoring to investigate the effectiveness of a novel low-dose combination of bisoprolol/hydrochlorothiazide in adult patients with mild to moderate essential hypertension. Thirty-six patients with stable mild to moderate hypertension (sitting diastolic BP 95–114 mmHg) after a placebo run-in phase received oral bisoprolol/hydrochlorothiazide 5 mg/6.25 mg once daily for 4 weeks in a single-blind regimen. At office visits, BP and pulse were measured with statistically significant reductions (p<0.01) recorded after 2 and 4 weeks of treatment Twenty-four-h ambulatory BP monitoring at the completion of therapy revealed significant reductions (p<0.01) in both systolic and diastolic 24-h, daytime, and nighttime BP, compared with the end of the placebo treatment phase. Systolic and diastolic load were also reduced (p<0.01). The combination was well tolerated, and overall quality-of-life questionnaire scores indicated an improvement after bisoprolol/hydrochlorothiazide therapy (p = 0.02). No clinically significant changes from baseline in laboratory parameters were observed; in particular, serum potassium was unchanged. This is the first study to demonstrate the 24-h effectiveness of the bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination, using 24-h ambulatory BP monitoring. In addition, antihypertensive therapy with low doses of bisoprolol/hydrochlorothiazide in combination may improve tolerability.     

替米沙坦氢氯噻嗪胶囊与替米沙坦片治疗轻中度原发性高血压的临床研究

目的评价替米沙坦氢氯噻嗪胶囊治疗轻中度原发性高血压的有效性和安全性。方法符合入排标准的轻中度原发性高血压患者300例（8家医院）,先后经2周清洗期和4周替米沙坦片单药治疗期后,血压未达标者（90mmHg≤舒张压（diastolic blood pressure,DBP）〈110mmHg并且收缩压（systolic blood pressure,SBP〈180mmHg）按随机双盲对照原则分为两组,分别给予替米沙坦氢氯噻嗪胶囊（A组）与替米沙坦片（B组）。主要观察指标是双盲治疗8周后较开始双盲治疗时DBP绝对值的变化。其他观察指标还包括血生化指标、心电图、24小时动态血压（ABPM）参数等。结果 （1）共213例（A组即替米沙坦氢氯噻嗪胶囊组108例,B组即替米沙坦片组105例）完成该研究,33例失访,1例发生严重不良事件——心肌梗塞（研究者判断与本研究药物无关）。（2）双盲治疗8周后DBP绝对值的变化两组间有显著性差异（A组（12.66±10.76）mmHg,B组（7.89±12.15）mmHg,P=0.0203）。（3）A组总有效率、平均血压下降值、达目的的血压率均显著高于B组（P均〈0.05）。两组谷峰比值均〉50%。（4）两组不良事件发生率（A组21.8%;B组22.1%,P=0.9461）及与研究药物有关不良事件发生率（A组8.1%;B组9.8%,P=0.6264）均无显著性差异。结论替米沙坦氢氯噻嗪胶囊与替米沙坦片（80mg）对轻、中度原发性高血压患者有平稳长效的降压疗效和相同的安全性,且替米沙坦氢氯噻嗪胶囊的疗效优于单方的替米沙坦片。     

卡托普利与小剂量氢氯噻嗪合用治疗高血压疗效观察

目的：研究卡托普利与小剂量氢氯噻嗪合用对高血压患者的疗效及对代谢的影响。方法：５０例原发性高血压患者随机分为两组,第１组：单用卡手早１２．５ｍｇ～７５ｍｇ,每日２～３次。第２组,卡手早１２．５ｍｇ,每日２次,加服氢氯噻嗪１２．５ｍｇ,每日１次,两组治疗时间均为８周,测定治疗前后的基础血压,空腹血糖、血脂、血、血 到、 纱氮、肌酐以及有后的２４小时动态血压。 托普利加小剂量氢氯噻嗪组的总有效率及２４     

A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension

Objective: The comparison of antihypertensive effects between telmisartan and candesartan in patients with essential hypertension has been investigated in several small studies. The results were not consistent. We performed this meta-analysis determining the antihypertensive effect of telmisartan versus candesartan in these patients. Methods: We searched Pubmed, Web of Science, and Cochrane Central for all published studies comparing the antihypertensive effects between telmisartan and candesartan in patients with essential hypertension. Results: The antihypertensive effects were assessed in 302 patients included in 4 trials with a mean follow-up of 10 ± 4 weeks. There were no significant differences between telmisartan and candesartan in reduction of systolic blood pressure (SBP) and diastolic BP (DBP) in patients with essential hypertension (weighted mean differences (WMD) for SBP 1.98 mm Hg (95% confidence interval (CI), ?0.53, 4.49), p > 0.05; WMD for DBP 0.26 mm Hg (95% CI, ?1.65, 2.16), p > 0.05), respectively. In a sub-analysis including 2 randomized studies, there was not a significant difference for the reduction of SBP (WMD 0.90 (95% CI, ?2.88, 4.68) mm Hg, p > 0.05) or DBP (WMD ?0.80 (95% CI, ?3.40, 1.81) mm Hg, p > 0.05) treated with telmisartan or candesartan. Conclusions: This meta-analysis provides the evidence that the antihypertensive effects of telmisartan and candesartan are similar on SBP and DBP reduction in patients with essential hypertension, suggesting that strict designed randomized controlled trial would be helpful to compare antihypertensive effects of angiotensin II receptor blockers (ARBs) and improve the choice of ARBs in antihypertensive therapy.     

Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension

BACKGROUND: The efficacy of losartan (L) in combination with hydrochlorothiazide (HCTZ) has been demonstrated to reduce blood pressure. However, there are limited data on the effects of L/HCTZ combinations versus HCTZ monotherapies in reducing ambulatory systolic blood pressure. The aim of this study was to compare the effects of these treatment approaches in patients with ambulatory systolic hypertension. METHODS: Patients were randomized to receive L 50 mg (n = 60) or HCTZ 12.5 mg (n = 60) for 6 weeks. Patients were then force-titrated to L 50/HCTZ 12.5 mg and to L 100/HCTZ 25 mg or were sham-titrated to HCTZ 12.5 mg and force-titrated to HCTZ 25 mg, respectively. Clinic and 24-h ambulatory blood pressure (ABP) were measured at baseline and after each 6-week treatment period. RESULTS: We found that L 50 and HCTZ 12.5 induced significant and similar decreases in clinic and ABP. The combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided significantly greater decreases in clinic and ABP than did HCTZ monotherapies. The L 50/HCTZ 12.5 and L 100/HCTZ 25 combinations provided significant additional decreases in systolic/diastolic ABP during daytime (-5.3/-2.0 mm Hg; P <.001 and -5.8/-3.4 mm Hg; P <.001) and the other periods of the 24-h interval compared with the levels achieved by the previous treatment, indicating a clear dose-response relationship. However, increasing the dose of HCTZ from 12.5 mg to 25 mg was not associated with additional ABP reductions. CONCLUSIONS: Combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided greater reductions in clinic and ABP than HCTZ monotherapies, with a clear dose-response relationship with regard to ABP. These results support the use of ABP monitoring when assessing the efficacy of antihypertensive therapies.     

Comparison of acebutolol with and without hydrochlorothiazide versus carvedilol with and without hydrochlorothiazide in black patients with mild to moderate systemic hypertension.

In the present study, we assessed the antihypertensive efficacy of acebutolol 200 mg versus carvedilol 25 mg once daily, given as monotherapy for 3 months to 40 black patients (20 patients in each group, mean age 53+/-10 years, 24 women) with mean blood pressure (BP) during the day >90 and <110 mm Hg. Patients in whom blood pressure could not be controlled took medication, which was increased at 3-month intervals as follows: step 2, acebutolol 200 mg or carvedilol 25 mg plus hydrochlorothiazide 12.5 mg once daily; step 3, acebutolol 400 mg or carvedilol 50 mg plus hydrochlorothiazide 25 mg once daily. Overall, significant but modest BP reduction was achieved with both beta blockers at 3 months. In the acebutolol group, 24-hour BP decreased from 142+/-15/94+/-7 mm Hg to 138+/-16/89+/-8 mm Hg (p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 145+/-15/98+/-5 mm Hg to 140+/-14/93+/-7 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs. baseline). In the carvedilol group, 24-hour BP decreased from 145+/-11/93+/-6 to 138+/-16/87+/-9 mm Hg (p<0.05 for systolic BP and p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 149+/-10/99+/-5 to 141+/-16/91+/-87 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs baseline). At 12 months, most patients required combination therapy to achieve BP control. The control (mean day diastolic BP <90 mm Hg) and response (mean day diastolic BP decrease > or =10 mm Hg) rates at 12 months were 59% and 82% in the acebutolol and 78% and 78% in the carvedilol groups, respectively. In conclusion, acebutolol or carvedilol in combination with hydrochlorothiazide, rather than acebutolol or carvedilol alone, should be considered as first-line antihypertensive therapy in black patients with mild to moderate hypertension.     

Time to achieve blood-pressure goal: influence of dose of valsartan monotherapy and valsartan and hydrochlorothiazide combination therapy

BACKGROUND: Our objective was to assess time to achieve blood-pressure (BP) goal with incremental doses of valsartan alone, and together with hydrochlorothiazide (HCTZ), in patients with uncomplicated hypertension. METHODS: This analysis pooled patient-level data from nine randomized, double-blind, fixed-dose, placebo-controlled trials (N = 4278) of once-daily valsartan 80 mg, 160 mg, and 320 mg, and valsartan/hydrochlorothiazide (HCTZ) 80/12.5 mg, 160/12.5 mg, 160/25 mg, 320/12.5 mg, and 320/25 mg. Kaplan-Meier methods estimated the cumulative proportion of patients achieving BP <140/90 mm Hg over 8 weeks and the median time to BP goal. The HCTZ 12.5-mg and 25-mg doses were pooled for the time-to-goal analysis in patients receiving combinations with valsartan 160 mg or 320 mg. RESULTS: Overall, the median time-to-goal was 8.1 weeks with valsartan 160 mg, 6.1 weeks with valsartan 320 mg, 2.6 weeks with valsartan 160 mg/HCTZ, and 2.1 weeks with valsartan 320 mg/HCTZ. In patients with stage 2 hypertension, the median time-to-goal was 4.3 weeks with valsartan 160 mg/HCTZ and 2.4 weeks with valsartan 320 mg/HCTZ. Goal rates by Week 4 for valsartan/HCTZ exceeded rates by Week 8 with the same doses of valsartan alone. Overall, the proportion that achieved BP goal by Week 8 was 32.6% with valsartan 80 mg, 48.4% with valsartan 160 mg, 54.2% with valsartan 320 mg, 74.6% with valsartan 160 mg/HCTZ, and 84.8% with valsartan 320 mg/HCTZ, versus 24.2% with placebo. With valsartan 320 mg/HCTZ, 75.8% of stage 2 patients and 94% of stage 1 patients reached BP goal by Week 8. Discontinuation rates due to adverse events were generally low across doses. CONCLUSIONS: In both stage 1 and stage 2 hypertension, BP control is achieved more frequently and promptly when patients receive higher doses of valsartan monotherapy or valsartan combination therapy, with a favorable benefit-risk profile.     

Efficacy and safety of eplerenone in the management of mild to moderate arterial hypertension: Systematic review and meta-analysis

Background

The role of eplerenone in arterial hypertension has been investigated only in small studies. To systematically assess the efficacy and tolerability of eplerenone in patients with mild to moderate arterial hypertension, we did a meta-analysis of controlled randomized trials.

Methods

We performed an electronic literature search of Medline, Pubmed, Scopus and Cochrane databases for studies published up to March 31, 2014. Randomized studies comparing eplerenone with placebo or other antihypertensive drugs for net reduction of systolic and diastolic blood pressures (SBP; DBP) from baseline and for incidence of adverse events were considered. Weighted mean differences (WMD) and odds ratios with 95% confidence interval were calculated for continuous and dichotomous data, respectively.

Results

A total of 11 trials and 3566 patients were overall included. Compared to placebo, eplerenone significantly reduced either SBP [WMD − 8.07, 95% CI − 8.17 to − 7.96 mm Hg, p < 0.00001] and DBP [WMD − 4.08, − 4.15 to − 4.01 mm Hg, p < 0.00001]. In the overall comparison, reduction of both SBP and DBP with eplerenone was greater than other antihypertensive agents (WMD for SBP − 1.50 mm Hg, p < 0.0001; WMD for DBP − 0.54 mm Hg, p < 0.00001); this was essentially driven by a greater anti-hypertensive action vs enalapril and losartan for SBP and vs losartan for DBP. Rates of any adverse event were significantly higher with eplerenone than placebo (odds ratio 1.37, 95% CI 1.1 to 1.71; p = 0.005), whereas the occurrence of serious adverse events and hyperkalemia was similar. There was no difference between eplerenone and other antihypertensives in the frequency of any or serious adverse events, whereas hyperkalemia was more common with eplerenone (odds ratio 2.36, 95% CI 1.00 to 5.57; p = 0.05).

Conclusion

This study-level meta-analysis provides a robust evidence that eplerenone has a reassuring safety profile and is effective in lowering blood pressure in patients with mild-to-moderate hypertension; this effect is at least comparable to that of other anti-hypertensive agents (PROSPERO Registration No. CRD42014010071).     

Effect of the angiotensin II receptor blocker candesartan on fibrinolysis in patients with mild hypertension

Aim:  Impaired fibrinolysis is frequently observed in patients with the metabolic syndrome. Aim of the study was to examine the short-term effect of angiotensin II receptor blockade on the fibrinolytic system.
Methods:  Seventy-four patients with mild hypertension were randomly assigned to a 7-day treatment period with either 16 mg candesartan cilexetil or placebo. Several variables of the fibrinolytic system such as plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity as well as circulating t-PA/PAI-1 complexes were determined.
Results:  At baseline, the body mass index but not blood pressure was positively associated with PAI-1 antigen (r = 0.314, p < 0.01) and PAI-1 activity (r = 0.425, p < 0.01) but negatively with t-PA activity (r = −0.187, p < 0.05). A 7-day treatment with 16 mg candesartan cilexetil resulted in a significant greater reduction of diastolic blood pressure (−10.3 ± 10.8 mmHg vs.−5.8 ± 8.5 mmHg, p = 0.03). However, there was no significant effect of candesartan on all parameters of the fibrinolytic system under investigation, i.e. circulating PAI-1 antigen, PAI-1 activity, t-PA antigen, t-PA activity and t-PA/PAI-1 complexes. Furthermore, candesartan did not affect the characteristic circadian pattern of the variables of the fibrinolytic system.
Conclusion:  We conclude that short-term blockade of the angiotensin II receptor subtype 1 with candesartan does not have an impact on fibrinolysis in patients with mild hypertension.     

瑞舒伐他汀和替米沙坦对原发性高血压并发阵发性心房纤颤治疗的影响

目的:观察瑞舒伐他汀和替米沙坦对原发性高血压(EH)并发阵发性心房纤颤(AF)患者心电图P波时限和离散度及AF发生率的影响。方法:EH并发阵发性AF患者56例,随机分为2组:替米沙坦(80 mg/d)加瑞舒伐他汀(10 mg/d)组(联合用药组)和替米沙坦(80 mg/d)组。共观察6个月。分别于用药前后测定12导联体表心电图中P波的时限和P波离散度及AF发生率。结果:用药后两组均可使EH并发阵发性EH患者心电图P波的时限和P波离散度减小,组间比较显示,联合用药组的作用优于单用替米沙坦组。结论:瑞舒伐他汀合用替米沙坦对EH并发阵发性AF患者窦律的维持及预防AF发生的作用优于单用替米沙坦。