简讯

缬沙坦与氨氯地平联合使用降压效果良好该研究系一“实时”研究(Am Society of Hyper-tension2007Scientific Sessions,May21,2007,Chicogo IL),收治病人894名,都用过单药治疗,如利尿剂、钙拮抗剂、β受体阻滞剂、血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂。疗效不好者,再入选,平均入选时血压150/90mm Hg。443名病人随机分入氨氯地平5mg(缬沙坦160mg)组,另有451名病人分入氨氯地平10mg(缬沙坦160mg)组。8周后如血压下降不理想,可加用氢氯噻嗪,初始量12·5mg,必要时可加到25mg。联合治疗后16周,病人收缩压下降幅度较单药治…     

左旋氨氯地平、替米沙坦及氢氯噻嗪同时或不同时给药对反杓型高血压的影响

目的探讨左旋氨氯地平、替米沙坦及氢氯噻嗪同时或不同时给药对反杓型高血压的影响。方法收缩压(SBP)<180 mm Hg,舒张压(DBP)91~109 mm Hg,年龄>45岁的反杓型高血压患者200例,随机分为不同时给药组:晨服替米沙坦40 mg、氢氯噻嗪10 mg,晚服左旋氨氯地平5 mg;同时给药组上述3种药物均晨服。治疗前及治疗后8 w行动态血压监测检查。结果治疗8 w后两组24 h SBP/DBP分别降低30.28/13.12 mm Hg和29.98/13.87 mm Hg,日间SBP/DBP分别降低24.26/10.39 mm Hg和26.69/12.24 mmg,夜间SBP/DBP分别降低37.50/17.71 mm Hg和32.94/15.41 mm Hg,均较治疗前明显下降(P<0.05);治疗后两组24 h SBP/DBP相较无明显差异(P>0.05),而治疗后不同时给药组日间SBP/DBP较同时给药组高(P<0.05),夜间SBP/DBP较同时给药组低(P<0.05)。不同时给药组的逆转率为61%,高于同时给药组的为31%(P<0.05)。结论左旋氨氯地平、替米沙坦及氢氯噻嗪两种服药方法均能有效控制24 h血压,不同时给药能更好地逆转杓型血压。     

苯磺酸左旋氨氯地平片与厄贝沙坦/氢氯噻嗪片联合治疗高血压的疗效评价

目的 观察苯磺酸左旋氨氯地平片(2.5mg)与厄贝沙坦/氢氯噻嗪片(含厄贝沙坦150mg,氢氯噻嗪12.5mg)联合治疗高血压的临床疗效.方法 选择高血压患者72例,随机分为3组:A组(n=23)口服苯磺酸左旋氨氯地平片2.5mg,1次/d;B组(n=19)口服厄贝沙坦/氢氯噻嗪片150mg,1次/d;C组(n=30)晨服厄贝沙坦/氢氯噻嗪片150mg,睡前服用苯磺酸左旋氨氯地平片2.5mg,1次/d;疗程均为12周.结果 3组患者血压均有下降,A组总有效率为65.2%,B组为63.1%,C组为93.3%.结论 苯磺酸左旋氨氯地平片联合厄贝沙坦/氢氯噻嗪片用于治疗高血压比单用苯磺酸左旋氨氯地平片或厄贝沙坦/氢氯噻嗪片更有效、安全,值得推广.     

缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的影响

目的 比较缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性及一氧化氮、内皮素的影响.方法选取61例2、3级老年高血压患者,随机分为两组,分别给予缬沙坦+氨氯地平或缬沙坦+氢氯噻嗪行降压治疗,观察入选时、治疗第8周和第16周各种相关指示的变化.人选时检测血脂、空腹血糖、血尿酸,试验各个阶段监测24 h动态血压,检测血浆一氧化氮、内皮素水平.结果在患者入选时、治疗第8周和第16周三个时间点,缬沙坦+氨氯地平组和缬沙坦+氢氯噻嗪组24 h血压及白昼血压比较差异无统计学意义.治疗第16周,缬沙坦+氨氯地平组晨峰收缩压较缬沙坦+氢氯嚷嗪组明显降低[(22.6±8.8)mm Hg(1 mm Hg=0.133 kPa)比(26.3±13.7)mm Hg,P＜0.05];缬沙坦+氨氯地平组及缬沙坦+氢氯噻嗪组24 h收缩压变异性(SBPV)进行性降低[缬沙坦+氨氯地平组:(12.5±2.8)mm Hg比(10.2 ±2.2)mm Hg比(8.8±1.6)mm Hg,P＜0.01;缬沙坦±氢氯噻嗪组:(12.5±2.5)mmHg比(10.7±2.2)mm Hg比(9.6±2.0)mmHg,P＜0.01],缬沙坦+氨氯地平组及缬沙坦+氢氯噻嗪组白昼SBPV明显降低[缬沙坦+氨氯地平组:(12.2±3.0)mm Hg比(10.1±2.3)mm Hg比(8.4±1.9)mm Hg,P＜0.01;缬沙坦+氢氯噻嗪组:(11.8±2.7)mm Hg比(10.4±1.9)mm Hg比(9.6±2.2)mm Hg,P＜0.01],缬沙坦+氨氯地平组24 h舒张压变异性(DBPV)显著降低[(15.5±3.4)mm Hg比(13.0±3.5)mm Hg比(12.3±2.5)mm Hg,P＜0.01],缬沙坦+氢氯噻嗪组24 h DBPV无显著性变化;缬沙坦+氨氯地平组第16周白昼SBPV低于缬沙坦+氢氯噻嗪组[(8.4±1.9)mm Hg比(9.6 ±2.2)mm Hg,p＜0.05],缬沙坦+氨氯地平第8周、第16周的24 h DBPV、白昼DBPV低于缬沙坦+氢氯噻嗪组(P ＜0.01～0.05);缬沙坦+氨氯地平组一氧化氮进行性升高[(27.3±13.6)μmol/L比(47.2±16.3)μmol/L比(69.5±18.9)μmol/L,P＜0.01]、内皮素进行性降低[(45.3±8.0)ng/L比(37.4±3.9)ng/L比(34.2±4.4)ng/L,P＜0.01];缬沙坦+氢氯噻嗪组一氧化氮进行性升高[(33.5±13.9)μmol/L 比(49.7±21.9)μmol/L比(66.7 ±24.7)μmol/L,P＜0.01]、内皮素显著降低[(46.6±10.4)ng/L比(37.0±5.4)ng/L比(36.1±8.2)ng/L,P＜0.01].治疗第8周,缬沙坦+氨氯地平组收缩压变异性的降幅与一氧化氮的升幅有相关性(r =0.401,P=0.025).结论缬沙坦联合氨氯地平或氢氯噻嗪均能降低老年高血压患者血压变异性、改善血管内皮功能,缬沙坦联合氨氯地平可能更适合于老年高血压患者.     

血管紧张素受体拮抗剂与钙拮抗剂或利尿剂联用对家庭血压变异性的影响

有报道显示每日间家庭血压变异性和心血管风险增加相关。该研究旨在验证与血管紧张素受体拮抗剂(angiotensin receptor blocker,ARB)+利尿剂相比,ARB+钙拮抗剂是否能更大程度降低家庭血压变异性,并探索其潜在机制。方法:入选单用奥美沙坦治疗12周的高血压患者207例,随机分为氢氯噻嗪组(合用氢氯噻嗪,n=104)或阿折地平组(合用阿折地平,n=103),联合用药24周,每4周随访1次。     

噻嗪类利尿剂、氯沙坦及其复方制剂对高血压患者的血清尿酸水平的影响

目的 观察原发性高血压病(EH)患者高尿酸血症的流行情况,以及噻嗪类利尿剂、血管紧张素受体拮抗剂氯沙坦和氯沙坦+氢氯噻嗪6周降压治疗后EH患者血清尿酸(SUA)和电解质的变化.方法 收集福州4家医院近3年连续的EH患者共1080例,其中男女之比662:418,平均年龄(60.9±12.3)岁,治疗前后血压记录完整者1000例,肾功能和电解质完整者600例.结果 EH患者合并高尿酸血症的发生率为25.83%(279/1080),与EH组比较,EH合并高尿酸血症组患者体质指数、肌酐升高,内生肌酐清除率降低(P分别<0.05和0.01).降压治疗6周末69.40%(694/1000)患者收缩压<140 mm Hg(1 mm Hg=0.133 kPa),85.30%(853/1000)患者舒张压<90 mm Hg.不同降压药物治疗后SUA和血钾的变化:低剂量利尿剂组SUA平均升高(43.81±71.79)μmol/L(P<0.0001),氯沙坦组平均下降(44.96±90.63)μmol/L(P<0.01,100 mg组优于50 mg组),氯沙坦+氢氯噻嗪组平均下降(7.46±84.72)μmol/L,三组药物治疗后SUA之间的差异有统计学意义;低剂量利尿剂组血钾平均下降(0.30±0.44)mmol/L(P<0.01),与氯沙坦组[(0.06±0.43)mmol/L]和氯沙坦+氢氯噻嗪组[(-0.04±0.44)mmol/L]比较,差异也有统计学意义.结论 EH患者25.83%合并高尿酸血症;高血压合并高尿酸血症者有体质指数增加和肾功能损害趋势;低剂量噻嗪类利尿剂会加重SUA增高和低血钾,氯沙坦可剂量依赖性的降低SUA,而氯沙坦+氢氯噻嗪介于两者之间.     

肢端肥大症致高血压1例

正1临床资料患者女,56岁,高血压病史16年,血压最高达220/110mm Hg(1mm Hg=0.133kPa),平素口服酒石酸美托洛尔片25mg,2次/d,氨氯地平5、厄贝沙坦氢氯噻嗪150mg/d,地巴唑10mg,3次/d。血压波动于160~170/100mm Hg,先后多次就诊于当地医院及天津市蓟州区人民医院(我院),并于当地医院行肾素、血管紧张素醛固酮检查未见异常,空腹血糖6.02、总胆     

氨氯地平和坎地沙坦联用对原发性高血压尿微量清蛋白的影响

目的 评价联合应用钙拮抗剂(氨氯地平)和血管紧张素Ⅱ受体拮抗剂(坎地沙坦)及单用对原发性高血压患者血压及尿微量清蛋白(MAU)的影响.方法 高血压1、2级伴MAU阳性门诊患者90例,随机分为联合用药组(氨氯地平5mg/d+坎地沙坦8mg/d,n=30)、单用氨氯地平组(5mg/d,n=30)和单用坎地沙坦组(8mg/d,n=30).治疗2周后单用组血压未达标者剂量加倍以达目标血压,疗程共6个月.记录治疗前、治疗后3个月和6个月血压、MAU的变化及可能发生的不良事件.结果 治疗3个月后3组血压均较治疗前明显下降(P＜0.01),且联合组较坎地沙坦组降压更明显(P＜0.01),与氨氯地平组无明显差异,治疗6个月后联合组较氨氯地平组显示降压更有效(P＜0.05);3组治疗3个月后MAU均较治疗前明显减少(P＜0.01),且随时间延长作用更明显.两个单用组与联合用药组比较,坎地沙坦组优于氨氯地平组(P＜0.01),联合组优于坎地沙坦组(P＜0.05).结论 钙拮抗剂类药物和血管紧张素Ⅱ受体拮抗剂联用较单一药物剂量加倍对血压控制情况有明显优势,且能更好改善高血压患者的早期肾损害,提示早期肾损害者应尽早联合降压治疗.     

小剂量左旋氨氯地平、替米沙坦及氢氯噻嗪同时和不同时给药对血压晨峰的影响

目的 探讨小剂量左旋氨氯地平、替米沙坦及氢氯噻嗪同时与不同时给药对轻中度高血压患者血压晨峰（MBPS）的影响.方法 选择我院2011年5月至2014年5月门诊及住院的高血压患者138例,男性86例,女性52例.入选者收缩压（SBP）＜180 mm Hg,舒张压（DBP）91～109 mm Hg,年龄＞45岁,24 h动态血压监测（ABDM）具有MBPS现象.随机分为2组：Ⅰ组（不同时给药组,70例）晨服替米沙坦40 mg和氢氯噻嗪10 mg,晚服左旋氨氯地平2.5 mg;Ⅱ组（同时给药组,68例）以上三种药物均晨服.所有病例治疗前及治疗8周后进行ABPM监测.结果 治疗8周后,Ⅰ组和Ⅱ组的24h SBP/DBP均较治疗前分别降低17.34/10.26 mm Hg和16.64/10.42 mm Hg,日间SBP/DBP分别降低15.48/9.86 mm Hg和17.36/10.28 mm Hg,均较治疗前明显降低（P＜0.01）,两组间降低幅度未见统计学差异（P＞0.05）.两组夜间SBP/DBP分别降低21.52/11.22 mm Hg和15.82/10.14 mm Hg,均较治疗前明显降低（P＜0.01）;Ⅰ组治疗后降低幅度较Ⅱ组明显,两组比较差异有统计学意义（P＜0.05）.治疗前与治疗8周后清晨收缩压差值（MSBPD）Ⅰ组分别为（37.26±10.34）mm Hg和（23.14±7.82）mm Hg,治疗后显著降低（P＜0.01）;Ⅱ组分别为（37.48±10.32）mm Hg和（29.34±8.46）mmHg,治疗后明显降低（P＜0.05）,两组治疗后比较,差异有统计学意义（P＜0.05）.结论 对于晨峰高血压患者,小剂量左旋氨氯地平、替米沙坦及氢氯噻嗪无论同时还是不同时给药均能有效控制24h、日间和夜间血压;而不同时给药治疗夜间血压优于同时给药,尤其控制MBPS现象更明显.     

常见降压药小剂量联合治疗老年非杓型高血压的疗效

目的探讨常见降压药(替米沙坦、氢氯噻嗪、左旋氨氯地平)小剂量联合治疗老年非杓型高血压的疗效。方法选取2012年9月至2014年2月该院收治的非杓型高血压患者126例,随机分为联合治疗组、对照A组(替米沙坦组)、对照B组(左旋氨氯地平),每组42例。检测治疗前后3组患者动态血压变化、非杓型高血压逆转情况、疗效和不良反应发生情况。结果治疗后8 w后,3组患者血压均明显低于治疗前(P0.05);联合治疗组血压恢复情况明显优于对照A组和对照B组(P0.05);两个对照组血压下降情况之间差异无统计学意义(P0.05)。联合治疗组治疗后转为杓型血压的患者比例明显高于对照组(P0.01);对照B组非杓型高血压逆转率明显高于对照A组(P0.01)。治疗8 w后,联合治疗组治疗总有效率明显高于对照组(P0.05)。对照组不良反应发生率明显高于联合治疗组(P0.05)。结论替米沙坦、氢氯噻嗪、左旋氨氯地平小剂量联用可有效地控制24 h血压,更好地逆转老年非杓型高血压,具有更好的疗效和安全性。     

Improving Blood Pressure Control: Increase the Dose of Diuretic or Switch to a Fixed‐Dose Angiotensin Receptor Blocker/Diuretic? The Valsartan Hydrochlorothiazide Diuretic for Initial Control and Titration to Achieve Optimal Therapeutic Effect (Val‐DICTATE) Trial

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.     

Effects of high dose olmesartan medoxomil plus hydrochlorothiazide on blood pressure control in patients with grade 2 and grade 3 hypertension

High dose (40 mg) olmesartan medoxomil (OM) blocks the angiotensin II receptor, significantly reducing blood pressure (BP). Adding hydrochlorothiazide (HCTZ) to OM increases efficacy, but has not been evaluated in patients inadequately controlled by OM 40 mg. Patients with grade 2 and grade 3 hypertension with inadequately controlled BP (seated diastolic blood pressure [SeDBP] 90-115 mm Hg and seated systolic blood pressure [SeSBP] 140-180 mm Hg, plus ambulatory BP criteria) after 8 weeks of OM 40 mg open-label treatment were randomized to 8 weeks of double-blind treatment with OM/HCTZ 40/25 (n=140), 40/12.5 (n=278), 20/12.5 mg (n=280) or OM 40 mg (n=274). Treatment with OM/HCTZ 40/25 mg and 40/12.5 mg significantly reduced SeDBP (-5.3 and -3.4 mm Hg, respectively), and SeSBP (-7.4 and -5.2 mm Hg, respectively), vs OM 40 mg monotherapy (P<0.0001 for each) in patients inadequately controlled on OM 40 mg alone. OM/HCTZ 40/12.5 mg reduced SeSBP significantly more than OM/HCTZ 20/12.5 mg (-2.6 mm Hg, P=0.0255), and also produced a further reduction in SeDBP vs the lower dose. All treatments were well tolerated, with similar low proportions of patients reporting treatment-emergent adverse events in all treatment groups. In conclusion, adding HCTZ to OM 40 mg significantly improves BP reductions and target BP rates in harder-to-treat patients and a clear dose-response was observed for efficacy.     

Studies on the Mechanism of the Enhancement of the Antihypertensive Activity of Captopril by A Diuretic in Spontaneously Hypertensive Rats

Captopril (30 mg/kg/day orally for two days) in spontaneously hypertensive rats (SHR) inhibited serum angiotensin converting enzyme (ACE) activity 92.3%; increased plasma renin activity (PRA) 18-fold and reduced mean arterial blood pressure (MABP) 19 mm Hg. Hydrochlorothiazide (HCTZ) (100 mg/kg-day 1; 10 mg/kg-day 2, orally) increased PRA 3-fold but did not affect serum ACE or MABP. HCTZ plus captopril inhibited serum ACE 95.2%; increased PRA 38-fold and reduced MABP 47.5 mm Hg. Captopril or HCTZ plus captopril did not alter the responses of isolated aortic strips to norepinephrine (NE), serotonin, angiotensin II (AII) or isoproterenol. Pressor responses of conscious SHR to AII and NE were unaltered by captopril or HCTZ plus captopril although the bradykinin-induced depressor responses were significantly but equally potentiated. These results suggest that the potentiating effect of HCTZ is due to some mechanism that shifts the animal's blood pressure maintenance system to a renin-dependent state and is not due to changes in vascular reactivity.     

Valsartan alone or with a diuretic or ACE inhibitor as treatment for African American hypertensives: relation to salt intake

Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives, either alone, or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors. We performed a pilot, prospective, open label, randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq Na⁺/day) for 2 weeks and the same diet supplemented by 100 mEq Na⁺ for 4 weeks. After this evaluation, while continuing the Na⁺ supplementation, patients were randomized to valsartan 320 mg/day (n = 28), or the addition of hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks.Valsartan (160 mg/day) lowered blood pressure significantly in African American patients on both low salt (−6.4/−4.8 mm Hg: P < .001) and a high salt diet (−4.9/−3.8 mm Hg: P = .01). The high salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not significant). When comparing the efficacy of the three randomized therapeutic regimens while on the Na⁺ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of −10.5/−6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by −3.8/−3.3 mm Hg (P = not significant). The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant).We conclude that in our open label pilot study, the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor.     

The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide.

The long-term safety, tolerability, and antihypertensive effects of irbesartan/hydrochlorothiazide (HCTZ) were assessed in hypertensive patients (seated diastolic blood pressure [SeDBP] 95-110 mm Hg). Patients (n = 1098) completing two randomised, double-blind trials of irbesartan alone, HCTZ alone, irbesartan/HCTZ combinations, or placebo, took 1 year of open-label therapy starting with irbesartan 75 mg/HCTZ 12.5 mg once daily. If target blood pressure (BP) (<140/<90 mm Hg) was not achieved, the dose was titrated sequentially at 2- to 4-week intervals to irbesartan 150 mg/HCTZ 12. 5 mg, then to irbesartan 300 mg/HCTZ 25 mg. If necessary, adjunctive therapies were added. Mean changes in trough seated systolic BP/SeDBP at months 2, 6, and 12 were -19.1/-14.2 mm Hg (n = 941), -20.7/ -15.7 mm Hg (n = 948), and -20.6/-15.6 mm Hg (n = 898), respectively. From months 2 to 12, normalisation rates (trough SeDBP <90 mm Hg) ranged from 75-85% and total responder rates (normalised or >/=10 mm Hg trough SeDBP reduction) ranged from 81-91%, while target BP was achieved in 65-75% of patients. At all time-points, most patients (>/=87%) were receiving irbesartan/HCTZ alone. Eighty-two patients (7.5%) discontinued the study due to adverse events, with half of these events considered unrelated to study medication. There were no reports of serious adverse events related to study medication. Long-term therapy with irbesartan/HCTZ is safe, well tolerated, and maintains normalised BP in >80% of patients.     

Studies on the Mechanism of the Synergistic Antihypertensive Activity of Captopril and Hydrochlorothiazide Following Acute Administration in Spontaneously Hypertensive Rats

In spontaneously hypertensive rats (SHR), captopril at 30 and hydrochlorothiazide (HCTZ) at 100 mg/kg/day p.o. for 2 days lowered mean arterial blood pressure (MABP) 16 and 10 mm Hg, respectively. Treatment with the combination of captopril plus HCTZ for one day lowered MABP to the same extent as captopril alone, but produced a synergistic 44 mm Hg MABP lowering after the second day combination treatment. Bilateral ureteral ligation did not prevent the synergistic antihypertensive effect demonstrating that removal of electrolytes was not the cause of this effect. Cardiovascular responses to angiotensin-I and -II, norepinephrine or bradykinin did not differ in rats given the combination or captopril alone. After the combination treatment for one day, captopril but not HCTZ alone on the second day lowered MABP in rats to the same degree as in those receiving the combination treatment for 2 days, suggesting that the diuretic action per se is unimportant. Captopril and HCTZ increased plasma renin activity (PRA) but only the combination of captopril and HCTZ produced a greater and longer lasting increase of PRA. It is concluded that the mechanism for the synergism is the renin dependency, created by the combination of HCTZ and captopril, resulting in a greater role of the renin system in blood pressure control and increased responsiveness to angiotensin converting enzyme inhibition by captopril.     

Comparison of aliskiren/hydrochlorothiazide combination therapy with hydrochlorothiazide monotherapy in older patients with stage 2 systolic hypertension: results of the ACTION study

Patients with stage 2 systolic hypertension require sizable blood pressure (BP) reductions to achieve recommended targets. This randomized double-blind study compared a single-pill combination of the direct renin inhibitor aliskiren and hydrochlorothiazide (aliskiren/HCTZ) with HCTZ monotherapy in older patients (older than 55 years) with systolic BP ≥160 mm Hg and <200 mm Hg. After a 1- to 4-week washout, 451 patients were randomized to once-daily aliskiren/HCTZ 150/12.5 mg or HCTZ 12.5 mg for 1 week, and then double the doses for 7 weeks. Overall baseline BP was 168.8/91.4 mm Hg. At week 4 (primary) end point, aliskiren/HCTZ provided significantly greater BP reductions from baseline than HCTZ monotherapy (29.6/9.3 mm Hg vs 22.3/6.8 mm Hg) and resulted in a greater proportion of patients achieving BP goal of <140/90 mm Hg (51.1% vs 33.3%). Aliskiren/HCTZ therapy provides substantial BP reductions and may thus be a useful treatment option for older patients with stage 2 hypertension.     

A comparison of the tolerability of the direct renin inhibitor aliskiren and lisinopril in patients with severe hypertension

Patients with severe hypertension (>180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallel-group study compared the tolerability and antihypertensive efficacy of the novel direct renin inhibitor aliskiren with the angiotensin converting enzyme inhibitor lisinopril in patients with severe hypertension (mean sitting diastolic blood pressure (msDBP)>or=105 mm Hg and <120 mm Hg). In all, 183 patients were randomized (2:1) to aliskiren 150 mg (n=125) or lisinopril 20 mg (n=58) with dose titration (to aliskiren 300 mg or lisinopril 40 mg) and subsequent addition of hydrochlorothiazide (HCTZ) if additional BP control was required. Aliskiren-based treatment (ALI) was similar to lisinopril-based treatment (LIS) with respect to the proportion of patients reporting an adverse event (AE; ALI 32.8%; LIS 29.3%) or discontinuing treatment due to AEs (ALI 3.2%; LIS 3.4%). The most frequently reported AEs in both groups were headache, nasopharyngitis and dizziness. At end point, ALI showed similar mean reductions from baseline to LIS in msDBP (ALI -18.5 mm Hg vs LIS -20.1 mm Hg; mean treatment difference 1.7 mm Hg (95% confidence interval (CI) -1.0, 4.4)) and mean sitting systolic blood pressure (ALI -20.0 mm Hg vs LIS -22.3 mm Hg; mean treatment difference 2.8 mm Hg (95% CI -1.7, 7.4)). Responder rates (msDBP<90 mm Hg and/or reduction from baseline>or=10 mm Hg) were 81.5% with ALI and 87.9% with LIS. Approximately half of patients required the addition of HCTZ to achieve BP control (ALI 53.6%; LIS 44.8%). In conclusion, ALI alone, or in combination with HCTZ, exhibits similar tolerability and antihypertensive efficacy to LIS alone, or in combination with HCTZ, in patients with severe hypertension.     

Metoprolol succinate, a selective beta-adrenergic blocker, has no effect on insulin sensitivity

Insulin resistance is a risk factor for cardiovascular disease. Therapies to lower blood pressure should not decrease insulin sensitivity. Some b-adrenergic blocking agents can have an adverse effect on insulin sensitivity. This study examined the effect of extended-release metoprolol succinate on insulin sensitivity. Nondiabetics with hypertension (N=30) were started on (or changed to) hydrochlorothiazide (HCTZ) 12.5 mg daily for 14 days. Patients with blood pressure>140/90 mm Hg while taking HCTZ alone underwent an insulin clamp procedure to quantify insulin sensitivity. Metoprolol succinate treatment was begun at 50 mg daily and titrated to a dose that lowered blood pressure to <140/90 mm Hg. Following 12 weeks of metoprolol succinate plus HCTZ therapy, the insulin clamp procedure was repeated. On metoprolol succinate plus HCTZ treatment, there were no significant changes in insulin clamp measures of insulin sensitivity. Plasma cholesterol and low-density lipoprotein cholesterol decreased significantly on metoprolol succinate plus HCTZ. When b-blocker therapy is considered, metoprolol succinate can be used to treat hypertension without adverse metabolic effects.     

Direct Renin inhibition with aliskiren in obese patients with arterial hypertension

Current guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommend first-line treatment with a thiazide diuretic but do not provide specific guidance for obese patients. The renin system is activated in obesity-associated arterial hypertension. Therefore, we tested the hypothesis that the oral direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with hypertension (body mass index >or=30 kg/m(2); mean sitting diastolic blood pressure: 95 to 109 mm Hg) who had not responded to 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg. After a 2- to 4-week washout, 560 patients received single-blind HCTZ (25 mg) for 4 weeks; 489 nonresponders were randomly assigned to double-blind aliskiren (150 mg), irbesartan (150 mg), amlodipine (5 mg), or placebo for 4 weeks added to HCTZ (25 mg), followed by 8 weeks on double the initial doses of aliskiren, irbesartan, or amlodipine. After 8 weeks of double-blind treatment (4 weeks on the higher dose), aliskiren/HCTZ lowered blood pressure by 15.8/11.9 mm Hg, significantly more (P<0.0001) than placebo/HCTZ (8.6/7.9 mm Hg). Aliskiren/HCTZ provided blood pressure reductions similar to those with irbesartan/HCTZ and amlodipine/HCTZ (15.4/11.3 and 13.6/10.3 mm Hg, respectively), with similar tolerability to placebo/HCTZ. Adverse event rates were highest with amlodipine/HCTZ because of a higher incidence of peripheral edema (11.1% versus 0.8% to 1.6% in other groups). In conclusion, combination treatment with aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with hypertension who fail to achieve blood pressure control with first-line thiazide diuretic treatment.