伊贝沙坦治疗轻中度高血压疗效和安全性的临床研究

目的　为评价新一代血管紧张素ⅡAT1受体拮抗剂伊贝沙坦 (安博维 )降压疗效及安全性 ,并与氯沙坦相比较。方法　采用随机分组平行对照方法 ,将 12 0例轻、中度高血压患者分成伊贝沙坦组(6 0例 ) ,口服 15 0mg·d- 1和氯沙坦组 (6 0例 ) ,口服 5 0mg·d- 1。观察 8周。每 2周一次上午延迟 1～ 4小时用药并测诊室谷值坐位血压、心率 ,并观察不良反应。用药前及治疗第 4周和第 8周检测血液生化。第 4周谷值坐位血压仍大于 90mmHg者加用双氢克尿噻 12 5mg·d- 1。结果　第 4周伊贝沙坦与氯沙坦正常化率分别为 4 0 %和 35 % ,第 8周伊贝沙坦与氯沙坦组血压有效反应率分别为 78 3%和6 6 7% ,(P >0 0 5 )。两组治疗前、后平均谷值坐位舒张压有显著性差异P <0 0 1。伊贝沙坦组不良反应发生率 6 6 % ,氯沙坦组为 8 3% (P >0 0 5 )。两组部分病例加用小剂量双氢克尿噻后 ,谷值坐位舒张压进一步下降。谷值坐位舒张压下降幅度 ,伊贝沙坦组优于氯沙坦组 ,P <0 0 5。结论　伊贝沙坦与氯沙坦不良反应发生率均较低 ,伊贝沙坦降低谷值坐位舒张压更有效。建议生产伊贝沙坦与小剂量双氢克尿噻的复方制剂     

Irbesartan promotes erection recovery after nerve‐sparing radical retropubic prostatectomy: a retrospective long‐term analysis

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction following radical prostatectomy (RP) is among the most common and dreaded adverse effects of the surgery. Multiple studies confirm the potential benefit of various drug classes to accelerate the return of erectile function (EF) after RP. There is pre‐clinical evidence supporting the use of angiotensin‐receptor blockers (ARBs) for this purpose, although this has not been studied in humans. The present study shows that there may be a benefit in the recovery of EF post‐RRP in patients taking a daily dose of irbesartan, an ARB, following RRP. In addition, the use of irbesartan may curb the loss of stretched penile length which occurs postoperatively. Further study in the form of prospective, randomized, placebo‐controlled clinical trials are necessary to confirm these findings.

OBJECTIVE

• ? To evaluate retrospectively the potential benefit of administering irbesartan, an angiotensin‐receptor blocker, to improve erectile function (EF) recovery after nerve‐sparing radical retropubic prostatectomy (RRP).

PATIENTS AND METHODS

• ? Before surgery potent patients who underwent nerve‐sparing RRP between April and December 2009 elected to start daily oral irbesartan 300 mg on postoperative day 1 (n= 17). A contemporaneously clinically matched cohort consisting of patients who declined irbesartan use served as the control group (n= 12).
• ? Postoperative ‘on demand’ use of erectile aids (phosphodiesterase type 5 [PDE5] inhibitors and intracavernous injections) was adopted.
• ? Potency was monitored by the administration of International Index of Erectile Function‐5 (IIEF‐5) questionnaires before surgery and at early (3 months) and long‐term (12 and 24 months) postoperative intervals.
• ? Stretched penile length (SPL) was measured both immediately and 3 months after surgery.

RESULTS

• ? EF status was no different between groups at baseline (P > 0.05).
• ? While the IIEF‐5 scores at 24 months after surgery were statistically similar between the two groups (control = 15.2 ± 2.0, irbesartan = 14.1 ± 3.1, P= 0.77), at 12 months the IIEF‐5 scores of the irbesartan group were significantly higher than those of the control group (14 ± 2.6 vs. 7.2 ± 1.6, P < 0.05).
• ? The proportional loss of SPL after RRP was less in the irbesartan than in the control group at 3 months (–0.9 ± 1.5% vs –5.6 ± 1.5, P < 0.05).

CONCLUSION

• ? Regular irbesartan use after nerve‐sparing RRP in patients with normal preoperative erectile function could improve EF recovery after surgery and mitigate early loss of SPL.

     

伊贝沙坦合并前列腺素E1治疗高血压病早期肾损害

目的　探讨伊贝沙坦合用前列腺素E1对高血压病早期肾损害的作用。方法　 4 3例早期高血压病肾损害患者随机分为实验组 (n =2 2 )和对照组 (n =2 1) ,先予以伊贝沙坦 15 0mg/d ,治疗6 0d后 ,实验组加用前列腺素E115d。两组均在治疗前、治疗后 6 0d、治疗后 75d分别测定血清肌酐、2 4h尿肌酐、2 4h尿蛋白定量、晨尿查尿微量白蛋白和尿 β2 -微球蛋白、N -乙酰 - β -D氨基葡萄糖苷酶 (NAG)并计算肌酐清除率 (CCr)。结果　两组治疗 6 0d后治疗前与治疗后相比肌酐清除率增加 ,2 4h尿蛋白定量、尿微量白蛋白、β2 微球蛋白均明显下降 (P <0 0 5 )。而实验组尿 β2 微球蛋白、尿N -乙酰 - β -D氨基葡萄糖苷酶在疗程结束后较治疗前和对照组均明显降低 (P <0 0 5 )。 结论　伊贝沙坦合前列腺素E1对高血压病早期肾损害有保护作用 ,优于单一应用伊贝沙坦。     

伊贝沙坦对血管平滑肌细胞分泌细胞因子的影响

目的 :探讨伊贝沙坦 （Irb）对血管平滑肌细胞 （VSMC）分泌细胞因子的影响。方法 :兔 VSMC分 6组处理 ,即对照组 ,低密度脂蛋白组 ,氧化低密度脂蛋白 （ox L DL）组 ,Irb不同浓度组 ,Irb不同时间组及 Irb+ox L DL 组。以酶联免疫法检测培养上清液中细胞因子 TNFα,IL- 6 ,IL- 8水平。结果 :ox L DL（5 0 m g/L）对 TNFα,IL- 6 ,IL- 8分泌水平于刺激后 8h增加至 6 .4～ 8.5倍 ;Irb呈浓度 （0 .0 1～ 10 0 μmol/L）、时间 （1～ 2 4 h）依赖地抑制基础及 ox L DL 刺激的细胞因子分泌 （与对照组比较均 P<0 .0 5 ）。结论 :Irb可能通过抑制基础及 ox L DL 刺激的细胞因子分泌对VSMC生物学功能发挥调节作用     

肾素-血管紧张素系统基因多态性与高血压病患者伊贝沙坦降压幅度关系的研究

目的：对原发性高血压患者采用血管紧张素Ⅱ受体拮抗剂（伊贝沙坦）单药治疗，在观察降压疗效的同时测定RAS基因多态性靶位点：ACEI／D、ACTM235T、AT1R 1166A／C、573T／C、1062A／G、-521C／T的基因型，旨在发现与血管紧张素Ⅱ受体拮抗剂降压疗效相关的基因多态性位点。方法：符合WHO／ISH高血压诊断标准轻、中度高血压患者117例，服用伊贝沙坦单药治疗8周，在临床观察疗效的同时，应用RFLP及PCR的方法对患者血白细胞基因组DNA进行RAS基因多态性位点ACEI／D、AGT M235T、AT1R 1166A／C、573T／C、1062A／G、-521C／T基因型的分析。结果：含ACED等位基因、的患者服用伊贝沙坦后SBP下降幅度明显大于Ⅱ型基因型患者，两者之间有统计学差异（P〈0．05）；含AT1R 573T等位基因的患者服用伊贝沙坦后收缩压下降幅度明显大于CC纯合基因型患者，两者之间有统计学差异（P〈0．05）；AGT M235T、AT1R 1166A／C、-521C／T各基因型之间BP下降幅度均无显著差异。所有入选患者未发现AT1R 1062A→G的变异。结论：肾素-血管紧张素系统基因多态性位点ACEI／D及AT1R 573T／C与ARB类药物的药物敏感性有一定相关性。     

厄贝沙坦对2型糖尿病SD大鼠胰岛结构和功能的影响

目的：观察厄贝沙坦干预对2型糖尿病（T2DM）大鼠胰岛结构和功能的影响,以探讨其保护胰岛结构和功能的可能机制.方法：40只SD大鼠随机分为4组,每组10只,即A组（普通饲料组）,B组（高糖高脂饲料组）,C组（T2DM对照组）、D组（厄贝沙坦干预组）.观察厄贝沙坦干预对T2DM大鼠血糖、胰岛素等胰岛结构和功能的影响.结果：D组与C组比较,空腹血糖下降25.08％,稳态模型评价胰岛素抵抗指数下降30.87％,ISI提高了11.93％,明显改善糖耐量.D组与C组大鼠比较,胰岛内β细胞相对量增加67.35％,胰岛β细胞内胰岛素水平增加43.86％,胰岛β细胞胰岛素mRNA表达水平增高9.79％.结论：厄贝沙坦干预可降低T2DM大鼠空腹血糖、HOMA-IR,提高ISI,改善胰岛结构和功能.     

The therapeutic advantage of combination antihypertensive drug therapy using amlodipine and irbesartan in hypertensive patients: Analysis of the post-marketing survey data from PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; safety and efficacy in patients with hypertension) study

Abstract

Two-thirds of hypertensive patients need a combination antihypertensive therapy to achieve the target blood pressure (BP). The PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in paTieNts with hypERtension) study is a prospective specific clinical use survey examining the efficacy and safety of 12-week treatment with amlodipine (AML) and Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current analysis was performed as to the BP control, adverse reactions, and the effects on laboratory data in patients treated with the combination of AML and irbesartan (IRB), namely the patients added AML to already taking IRB (AML add-on group, n?=?1202) and the patients added IRB to AML (IRB add-on group, n?=?1050). Both study groups showed distinct decreases in office BP at 4 week (p?<?0.001) and the antihypertensive effects were sustained to 12 week (p?<?0.001). The percentage of patients achieving BP?<?140/90?mmHg was ～70% in either group. Proteinuria and estimated glomerular filtration rate (eGFR) were significantly improved in hypertensive patients with baseline eGFR <60?ml/min/1.73?m². Serum uric acid was reduced either by adding AML or IRB, and the reductions were prominent in patients with serum uric acid >7?mg/dl. The incidence of adverse reactions was as few as 1.11% and there were no severe adverse reactions which hampered the continuation of combination therapy. In conclusion, combination antihypertensive therapy with AML and IRB effectively lowers BP without particular safety problems, reduces serum uric acid especially in patients with hyperuricemia and exhibits renoprotective effects in patients with chronic kidney disease.     

厄贝沙坦治疗轻、中度高血压病

目的 :评价厄贝沙坦治疗轻、中度高血压病的临床疗效和安全性。方法 :选取轻、中度高血压病病人 ,采用双盲双模拟、随机对照法 ,比较厄贝沙坦与氯沙坦的降压效果。经 2wk安慰剂导入期后 ,服厄贝沙坦 (5 8例 ) 75mg ,qd或氯沙坦 (5 9例 ) 5 0mg ,qd ,于wk 4末坐位舒张压≥ 12kPa者则剂量加倍 ,继续服用 4wk。厄贝沙坦组 17例病人与氯沙坦组 14例病人 ,分别于治疗前及治疗wk 8末行 2 4h动态血压监测。结果 :8wk治疗末 ,有效率厄贝沙坦组 83%、氯沙坦组 78% ,2组比较差异无显著意义 (P >0 .0 5 )。厄贝沙坦的谷 /峰值收缩压为 81% ,舒张压为 70 % ,氯沙坦分别为 75 % ,71%。 2组最常见的不良反应是头晕。结论 :对轻、中度高血压病 ,厄贝沙坦是一种有效、安全且耐受性好的降压药     

Redefining efficacy of antihypertensive therapies beyond blood pressure reduction--the role of angiotensin II antagonists

Antihypertensive efficacy must be redefined beyond blood pressure (BP) lowering per se to include reducing the cardiovascular complications of hypertension. Treatment decisions should be based on results from large clinical trials with relevant clinical outcomes. Several recent morbidity and mortality trials with angiotensin II receptor antagonists (AIIAs) provide an evidence-based rationale for the use of AIIAs in patients with hypertension. Studies with AIIAs in comparison to conventional antihypertensive agents showed improved morbidity and mortality outcomes in patients with hypertension and left ventricular hypertrophy (losartan) and diabetes mellitus (losartan and irbesartan). Trials with some members of the AIIA class (candesartan and valsartan) have not demonstrated such benefits in comparison to conventional agents, possibly due to differences in BP control during the trials. The results of these AIIA outcome trials have impacted on recently issued clinical guidelines for management of hypertension.     

缬沙坦胶囊、厄贝沙坦片治疗糖尿病肾病患者106例临床观察

目的前瞻性观察缬沙坦与厄贝沙坦对糖尿病肾病患者微量尿白蛋白及血压的影响。方法前瞻性观察106例2型糖尿病肾病患者,按数字表法将患者随机分为A、B两组,均采用相应的基础降糖治疗后,A组(n=51)患者加用缬沙坦80 mg/d,B组患者(n=55)用厄贝沙坦150 mg/d,12周为1个疗程,每疗程观察微量白蛋白尿及血压,共3个疗程。结果①缬沙坦及厄贝沙坦对微量尿白蛋白经3个疗程治疗后,差异有统计学意义(Z=-6.490,P<0.001)。两种药物对于微量尿白蛋白治疗在各疗程终点比较差异无统计学意义(P>0.05)。②缬沙坦及厄贝沙坦对血压经3个疗程治疗后差异有统计学意义(P<0.05)。两种药物对于收缩压治疗在各疗程终点比较,差异有统计学意义(P<0.05)。结论两组药物均有减少糖尿病肾病患者微量蛋白尿及降压作用,而厄贝沙坦比缬沙坦在降低血压方面更有优势。