3种药物(氨氯地平,坎地沙坦,咪达普利)小剂量联合治疗明显减少高血压糖尿病患者的尿微量白蛋白释出

目的 探讨3种药物,包括钙拮抗剂(左旋氨氯地平),血管紧张素转换酶抑制剂(ACEI)(咪达普利)和血管紧张素受体拮抗剂(ARB)(坎地沙坦)联合治疗方案对2型糖尿病高血压患者尿微量蛋白的影响.方法 高血压2型糖尿病伴尿微量蛋白阳性门诊或住院病人160例,按就诊顺序随机分4组:分别用坎地沙坦(4 mg/d) 左旋氨氯地平(2.5 mg/d)、坎地沙坦(4 mg/d) 咪达普利(5 mg/d,n=40)、咪达普利(5 mg/d) 左旋氨氯地平(2.5mg/d,n=40)和左旋氨氯地平(2.5 mg/d) 坎地沙坦(4 mg/d) 咪达普利治疗(5 mg,n=40),疗程3月.观察治疗前后血压、尿微量白蛋白变化.结果 4组血压均较治疗前明显降低(P<0.05),但治疗后4组间血压比较,差异无统计学意义;尿微量白蛋白4组均较治疗前减少(P<0.01),3种药联合治疗组比2种药联合治疗组下降更明显[坎地沙坦 左旋氨氯地平组:治疗前(40.5±9.6)mg/L比治疗后(25.2±6.2)mg/L;坎地沙坦 咪达普利组:治疗前(41.3±10.8)mg/L比治疗后(20.2±6.3)mg/Li咪达普利 左旋氨氯地平组:治疗前(43.3±10.4)mg/L比治疗后(20.6±6.4)mg/L;左旋氨氯地平 坎地沙坦 咪达普利联合组:治疗前(41.7±10.2)mg/L比治疗后(15.6±6.3)mg/L;P<0.05].结论 小剂量坎地沙坦、咪达普利及左旋氨氯地平联合应用在有效降压的同时,能改善2型糖尿病高血压患者早期肾损害,提示有早期肾损害者应尽早联合降压治疗.     

3种药物(氨氯地平,坎地沙坦,咪达普利)小剂量联合治疗明显减少高血压糖尿病患者的尿微量白蛋白释出

目的探讨3种药物,包括钙拮抗剂(左旋氨氯地平),血管紧张素转换酶抑制剂(ACEI)(咪达普利)和血管紧张素受体拮抗剂(ARB)(坎地沙坦)联合治疗方案对2型糖尿病高血压患者尿微量蛋白的影响。方法高血压2型糖尿病伴尿微量蛋白阳性门诊或住院病人160例,按就诊顺序随机分4组:分别用坎地沙坦(4 mg/d)+左旋氨氯地平(2.5 mg/d)、坎地沙坦(4 mg/d)+咪达普利(5 mg/d,n=40)、咪达普利(5 mg/d)+左旋氨氯地平(2.5mg/d,n=40)和左旋氨氯地平(2.5 mg/d)+坎地沙坦(4 mg/d)+咪达普利治疗(5 mg,n=40),疗程3月。观察治疗前后血压、尿微量白蛋白变化。结果 4组血压均较治疗前明显降低(P<0.05),但治疗后4组间血压比较,差异无统计学意义;尿微量白蛋白4组均较治疗前减少(P<0.01),3种药联合治疗组比2种药联合治疗组下降更明显[坎地沙坦+左旋氨氯地平组:治疗前(40.5±9.6)mg/L 比治疗后(25.2±6.2)mg/L;坎地沙坦+咪达普利组:治疗前(41.3±10.8)mg/L 比治疗后(20.2±6.3)mg/L;咪达普利+左旋氨氯地平组:治疗...     

瑞舒伐他汀对高血压患者的降压作用

目的 探讨瑞舒伐他汀是否对伴高脂血症的高血压患者有降压作用.方法 52例高血压合并高脂血症患者,分为两组:治疗组使用瑞舒伐他汀10 mg/d+坎地沙坦8 mg/d,对照组仅使用坎地沙坦8 mg/d,观察6个月,进行血压控制的疗效比较.结果 治疗组收缩压平均下降10.2 mmHg,对照组平均下降7.5 mmHg(P＜0.05);治疗组脉压差平均下降6 mmHg,对照组平均下降3mmHg(P ＜0.05);治疗组舒张压平均下降4.9mmHg,对照组平均下降4.2 mmHg(P ＞0.05).结论 瑞舒伐他汀与坎地沙坦合用比单用坎地沙坦对高血压合并高脂血症患者的收缩压和脉压有较好的降压作用,但对舒张压无显著影响.     

坎地沙坦酯联用氢氯噻嗪对高血压患者血压及左心室肥厚作用的观察

目的观察坎地沙坦酯联合氢氯噻嗪对原发性高血压患者的降压及左心室肥厚的逆转效果。方法选择76例原发性高血压伴左心室肥厚患者,随机分成两组,均给予坎地沙坦酯8mg/d,观察组在此基础上加氢氯噻嗪12．5mg/d,治疗6个月,观察治疗前、后血压变化并分另4用彩色多普勒超声诊断仪测量计算左心室心肌重量(LVM)、左心室重量指数(LVMI)。结果两组患者治疗后与治疗前比较SBP与DBP显著降低,且观察组治疗后较对照组低,差异有显著性意义(P＜0．05)；两组患者治疗前、后比较LVM、LVMI均显著降低,且观察组治疗后较对照组低,差异有显著性意义(P＜0．05)。结论坎地沙坦酯联用氢氯噻嗪降压以及逆转左心室肥厚比单用效果更好。     

坎地沙坦联合氢氯噻嗪治疗老年高血压患者的疗效及靶器官保护作用

目的 观察坎地沙坦联合氢氯噻嗪治疗老年高血压患者的疗效,以及其保护肾功能、逆转左心肥厚的临床效果.方法 选取2010年1月至2012年6月该院治疗的112名老年高血压患者,随机分为观察组(56例)和对照组(56例).两组患者均给予坎地沙坦8 mg/d治疗,观察组在此基础上联用氢氯噻嗪12.5 mg/d.治疗6个月后观察两组患者血压水平,以及左心室肌质量(LVM)、左心室重量指数(LVMI)和肾功各项指标.结果 治疗6个月后,观察组降压总有效率为89.3％,对照组为71.4％,两组相比差异具有统计学意义(P＜0.05).治疗后观察组LVM及LV-MI值明显低于对照组(P＜0.05),两组肾功能各项指标比较差异无统计学意义(P＞0.05).结论 坎地沙坦联合氢氯噻嗪治疗老年高血压降压效果优于单药治疗,且联合用药逆转左心室肥厚疗效更显著,但在肾功能保护方面联合用药并无明显优势.     

阿托伐他汀治疗高血压早期肾损害

目的 探讨阿托伐他汀对高血压早期肾损害的影响.方法 对55例经氨氯地平降压治疗达到高血压1级及以下标准的高血压患者随机分为实验组(n=27)和对照组(n=28),实验组予以阿托伐他汀10 mg/d和氨氯地平,对照组只给予氨氯地平.两组治疗前及治疗后12周检测24 h动态血压、空腹血脂和尿微量白蛋白(MAU)、尿β2-微球蛋白(β-2-MG)、N-乙酰-β-D氨基葡萄糖苷酶(NAG).结果 两组治疗后12周,24 h收缩压(SBP)和舒张压(DBP)、白昼和夜间SBP及DBP均较治疗前明显下降(P均＜0.01),但实验组下降更为显著(P均＜0.01),SBP和DBP平滑指数也优于对照组(P均＜0.01).治疗前后两组血脂无明显变化(P＞0.05);实验组MAU、β-2-MG和NAG较治疗前显著下降[MAU:(42.2±14.9)vs实验后 (18.2±12.1) mg/L,β-2-MG:(6.2±1.4)vs实验后 (3.5±0.8)mg/L,NAG:(28.5±14.7)vs实验后 (17.9±9.5)U/L,P均＜0.01],并低于同期的对照组(P＜0.01),对照组仅MAU较治疗前下降(P＜0.01).结论 阿托伐他汀具有一定的协同降压作用,并可能改善高血压早期肾损害的相关指标.     

坎地沙坦加氢氯噻嗪对轻中度高血压的疗效和安全性

目的 评价坎地沙坦加氢氯噻嗪(复方坎地沙坦酯片)对原发性高血压的降压疗效和安全性.方法 对原发性高血压患者经过2周清洗期后,进入坎地沙坦酯片8 mg单药治疗期,对4周后血压未达标者(达标血压为＜140/90 mm Hg),以随机、双盲双模拟、平行对照、多中心试验方法 ,分别服复方坎地沙坦酯片(坎地沙坦酯16.0mg/氢氯噻嗪12.5 mg)或坎地沙坦酯片16 mg单药治疗8周.结果 经过2周清洗期,共有392例进入单药治疗期,坎地沙坦酯8 mg单药治疗(n=353)2周后,血压下降值(10.2±0.6)/(6.5±5.7)mm Hg;4周的下降值为(10.8±10.9)/(6.6±6.1)mm Hg,4周血压达标率为15.3%(54/353例),组内比较,差异有非常显著意义(P＜0.01).在以后8周随机双盲对照期,复方坎地沙坦酯组(134例)与坎地沙坦酯单药组(142例)4周时的血压分别下降为(9.3±11.7)/(8.7±6.2)和(5.4±10.8)/(5.4±6.1)mm Hg;8周时为(11.1±11.2)/(10.7±6.6)和(7.8±11.1)/(7.8±6.3)mm Hg(组内及组间比较P＜0.01).随机期4周时联合治疗组血压达标率分别为64.9%(87/134),单药组为39.4%(56/142),8周时分别为79.9%(107/134)和51.4%(73/142)(组间比较P＜0.01).不良反应事件,在单药治疗期为6.2%(22/353),复方坎地沙坦组为2.9%(4/134),坎地沙坦酯组2.8%(4/142),组间比较差异无统计学意义(P＞0.05).结论 复方坎地沙坦酯片较之单用坎地沙坦对原发性高血压患者有较好的降压效果和耐受性.     

坎地沙坦与氨氯地平对高血压左室肥厚患者心功能和尿微量白蛋白的疗效观察

目的探讨坎地沙坦和氨氯地平对高血压患者左室肥厚和尿微量白蛋白的疗效。方法对83例门诊原发性高血压(1级、2级)并左室肥厚患者随机分为坎地沙坦组(42例)和氨氯地平组(41例),分别予以坎地沙坦和氨氯地平治疗。于受试前、后分别测定血压及二维彩色B超,检测室间隔(IVS)、左室后壁厚度(LVPW)、左室舒张末内径(LVDd)、E/A、左室射血分数(EF)和左室重量指数(LVMI),同时测定尿微量白蛋白、血清尿素氮和肌酐。结果两组在受试2周后与治疗前相比,血压均开始明显下降(P<0.01),两组降压疗效相比差异无统计学意义。两组24周测IVS、LVPW、LVDd和LVMI,较治疗前明显降低(P<0.01),EF和E/A升高(P<0.01),24周后坎地沙坦组优于氨氯地平组(P<0.05)。两组治疗4周后尿微量白蛋白都有明显下降(P<0.01)。坎地沙坦组随用药时间的延长,尿微量白蛋白不断降低,24周后明显优于氨氯地平组(P<0.01)。两组治疗前后血清尿素氮和肌酐无明显变化(P>0.05)。结论坎地沙坦和氨氯地平都有良好的降压作用,并且能逆转左室肥厚、降低尿微量白蛋白,但坎地沙坦的保护作用优于氨氯地平。     

坎地沙坦酯对老年高血压患者肾功能的影响

目的 观察坎地沙坦酯对老年高血压患者肾功能的影响.方法 老年高血压合并肾功能损害患者186例,随机分为对照组89例和治疗组97例,治疗组在对照组基础上加用坎地沙坦酯4 mg/d,随访6月观察其血肌酐(Cr)、尿素氮(BUN)、内生肌酐清除率(Ccr)的变化.结果 (1)两组药物均能明显降低血压(P＜0.05).(2)治疗组随访6月后Cr、BUN显著降低、Ccr显著增加(P＜0.01).对照组随访6月后Cr、BUN和Ccr无明显变化.结论 坎地沙坦酯在具有良好的降压作用之外对逆转老年高血压肾功能损害是有效可行的,且疗程越长者获益越大.     

无创性动态血压监测评价复方坎地沙坦酯片治疗原发性高血压患者的疗效

目的用无创性动态血压监测仪评价国产复方坎地沙坦酯片(坎地沙坦酯16 mg/氢氯噻嗪12.5 mg)对原发性高血压患者的降压疗效.方法原发性高血压患者经过2周清洗期后,进入坎地沙坦酯片8 mg单药治疗期,对4周后坐位血压未达标者(达标为血压＜140/90 mmHg),进行24小时动态血压监测,以随机双盲、平行对照试验方法,分别服用复方坎地沙坦酯片(复方坎地沙坦酯组,28例)或16 mg坎地沙坦酯片(坎地沙坦酯组,27例)治疗8周.比较两组服药前后24小时动态血压参数变化.观察组内与组间服药前后的不同时段的血压变化,谷峰比值及血压平滑指数.结果共55例患者完成动态血压监测,两组基础指标比较无差异.复方坎地沙坦酯组与坎地沙坦酯组药后收缩压/舒张压/平均动脉压全日平均值(24小时)、日间平均值(600～2200)、夜间平均值(2200～600)均明显下降,与同组基线值比较均有极显著性差异(P＜0.01).组间比较,复方坎地沙坦酯组收缩压/舒张压/平均动脉压全日平均值(24小时)、日间平均值(600～2200)、夜间平均值(2200～600)的降低幅度与坎地沙坦酯组比较均有极显著性差异(P＜0.01).服药谷峰比值(SBP/DBP)复方坎地沙坦酯组分别为99.36%(19.16/19.28 mmHg)和87.36%(10.14/11.61 mmHg),复方坎地沙坦酯组分别为54.42%(7.30/13.41 mmHg)和64.86%(6.43/9.91 mmHg).血压平滑指数(SBP/DBP)在复方坎地沙坦酯组为4.53/3.91,坎地沙坦酯组为1.29/1.52.结论复方坎地沙坦酯片对原发性高血压患者有较好的降压作用,复方制剂比单药降压幅度大、持续时间长.动态血压平均下降幅度日间＞全天＞夜间,收缩压＞舒张压.复方坎地沙坦酯控制血压更平稳.     

Long-term efficacy of combination therapy with losartan and low-dose hydrochlorothiazide in patients with uncontrolled hypertension

We evaluated the long-term efficacy of losartan and low-dose hydrochlorothiazide combination therapy in the treatment of hypertension. We enrolled 15 Japanese hypertensive outpatients whose 24-hour ambulatory blood pressure was >or= 135/80 mmHg after candesartan 8 mg (CND group; n = 10) monotherapy or amlodipine 5 mg (AML group; n = 5) monotherapy for 2 months or more. The monotherapy was then switched to losartan 50 mg and hydrochlorothiazide 12.5 mg combination therapy. Ambulatory blood pressure and indices of glucose and lipid metabolism were measured at the end of the monotherapy and after 3 and 12 months of the combination therapy. In the CND group, 24-hour blood pressure decreased significantly from 137 +/- 9/89 +/- 4 to 126 +/- 8/81 +/- 7 mmHg after 3 months (P < 0.05/ P < 0.001) and to 123 +/- 7/81 +/- 4 mmHg after 12 months (P < 0.01/P < 0.001). In the AML group, 24-hour blood pressure decreased significantly from 137 +/- 11/81 +/- 7 to 125 +/- 12/75 +/- 6 mmHg after 3 months (P < 0.05/P < 0.05) and to 124 +/- 9/77 +/- 7 mmHg after 12 months (P < 0.05/NS). There were significant decreases in systolic blood pressure during the daytime (6:00-21:30), nighttime (22:00-5:30) and early morning (6:00-8:00) after 12 months in both groups. No adverse changes in the indices of glucose or lipid metabolism were observed in either group. In conclusion, long-term combination therapy with losartan and low-dose hydrochlorothiazide was effective in the treatment of hypertensive patients whose blood pressure was not controlled by candesartan or amlodipine monotherapy alone.     

缬沙坦及贝那普利联合用药对高血压患者尿微量白蛋白的影响

目的观察血管紧张素II受体拮抗剂（ARB）类药物缬沙坦及血管紧张素转换酶抑制剂（ACEI）类药物贝那普利联合用药与大剂量单药（缬沙坦或贝那普利）对原发性高血压患者尿微量白蛋白（MAU）的影响。方法此研究为随机双盲实验。将119名有微量白蛋白尿的原发性高血压患者随机分为贝那普利组（10mg/d,n=42）、缬沙坦组（160mg/d,n=37）和联合用药组（贝那普利5mg/d＋缬沙坦80mg/d,n=40）。半量治疗4周后能耐受者增加至目标剂量,随访4周。分别于研究开始、治疗4周、8周时测定MAU和血压。结果治疗8周后降压幅度为：贝那普利组〔n=35,（15.8±3.4）/（10.0±1.8）mmHg〕,缬沙坦〔n=35,（14.7±3.7）/（9.8±1.6）mmHg〕,联合用药组〔n=38,（15.3±3.6）/（10.2±1.4）mmHg〕,3组比较血压差异无统计学意义;MAU降低幅度为：贝那普利组〔（65.4±9.5）mg/24h〕,缬沙坦〔（67.8±11.5）mg/24h〕,联合用药组〔（95.8±12.2）mg/24h〕,联合用药组较单药组效果显著,P均〈0.01。结论缬沙坦和贝那普利联合用药较加大剂量单药治疗的血压控制无差异,但对高血压患者的肾脏保护作用更强。     

Beneficial action of candesartan cilexetil plus amlodipine or ACE inhibitors in chronic nondiabetic renal disease

Although multiple antihypertensive agents are required to control blood pressure (BP) in chronic renal disease, it remains undetermined whether the combination therapy with angiotensin receptor blockers (ARB) plus calcium antagonists or angiotensin-converting enzyme inhibitors (ACEI) confers more preferable action on renal disease than the ARB monotherapy. In the present study, we compared the effect of the combination therapy with ARB plus calcium antagonists/ACEI on proteinuria with that of the ARB monotherapy in chronic nondiabetic renal disease. At 1 month of the drug treatment, the candesartan monotherapy (n=19) reduced BP from 154+/-3/93+/-2 to 146+/-3/88+/-2 mmHg (P<0.05), and a similar magnitude of BP reductions was observed with the combination therapy with candesartan plus ACEI/amlodipine (from 153+/-2/95+/-2 to 144+/-2/88+/-2 mmHg, P<0.05, n=39). The depressor action of these therapies was sustained throughout the 12-month treatment. In contrast, the reduction in proteinuria was greater with the combination therapy (-52+/-3% at 12 months, n=39) than with the candesartan monotherapy (-25+/-3%, n=19), although the baseline values of proteinuria were nearly the same in the candesartan monotherapy group (1.74+/-0.22 g/day) and the combination therapy group (2.10+/-0.19 g/day, P>0.2). Of note, the proteinuria-sparing effect did not differ between the candesartan+ACEI group and the candesartan+amlodipine group. In conclusion, the present study suggests more beneficial action of the combination therapy with ARB plus ACEI/amlodipine than the ARB monotherapy in nondiabetic renal disease. Since the reduction in BP was achieved to the same level, the distinct proteinuria-sparing action of these therapies is attributed to BP-independent mechanisms, which should vary depending on the agents used.     

Efficacy of combination therapy for systolic blood pressure in patients with severe systolic hypertension: the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study

Systolic hypertension is predominant among patients over 50 years of age, is a more important cardiovascular risk factor than diastolic blood pressure, and is more difficult to control than diastolic blood pressure. Consequently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends combination therapy as first-line treatment for patients with stage 2 hypertension. In the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study, 24-hour ambulatory blood pressure monitoring was used to identify patients with systolic hypertension and to determine the impact of 8 weeks of treatment with either amlodipine besylate/benazepril HCl 5/20 mg combination therapy (n=149), amlodipine besylate 5 mg (n=146), or benazepril HCl 20 mg (n=148). Combination therapy was significantly more effective in reducing systolic blood pressure and pulse pressure than either monotherapy (p<0.0001). Significantly greater percentages of patients in the combination group compared with either monotherapy achieved blood pressure control (p<0.0001). Adverse events were low in all three treatment arms, with less peripheral edema in the combination group than in the amlodipine-treated group. The combination of amlodipine besylate/benazepril HCl given to patients with stage 2 systolic hypertension resulted in significantly greater reductions in blood pressure and pulse pressure than those seen with monotherapy and was at least as well tolerated as the separate components. This data supports the recommendation of the JNC 7 for the use of combination therapy in patients with stage 2 hypertension.     

Amlodipine added to quinapril vs quinapril alone for the treatment of hypertension in diabetes: the Amlodipine in Diabetes (ANDI) trial

This randomized, comparative, parallel-group trial investigated strategies of blood pressure (BP)-lowering in patients with diabetes and hypertension. Patients not reaching goal BP (<130/80 mm Hg) after 4-week open-label treatment with quinapril 20 mg/d (n=374) received 40 mg/d quinapril (n=167) or 20 mg/d quinapril plus amlodipine besylate (5 mg/d; n=162) for 6 weeks. Patients receiving combination therapy vs monotherapy had significantly greater reductions in mean +/- SE sitting systolic BP (9.9+/-1.0 mm Hg vs 4.3+/-1.1 mm Hg; P<.001) and diastolic BP (6.5+/-0.6 mm Hg vs 2.7+/-0.6 mm Hg; P<.001). No significant differences between groups were observed in percentage of patients achieving goal BP (10.1% with combination therapy vs 8.2% with monotherapy). A clinically neutral effect was observed on high-sensitivity C-reactive protein in both groups. Treatments were well tolerated; fewer than 3% of patients in any group discontinued due to treatment-emergent or treatment-related adverse events. In diabetic hypertensive patients, 20 mg/d quinapril plus 5 mg/d amlodipine besylate was a more effective BP-lowering strategy than monotherapy with 40 mg/d quinapril.     

Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has reported that combinations of low doses of antihypertensive agents from different classes may provide additional antihypertensive efficacy and minimize the likelihood of dose-dependent adverse effects. Doxazosin and amlodipine, alone and in combination, were compared for efficacy in reducing blood pressure (BP) in 75 patients with predominantly moderate (Stage 2) hypertension. This was a double-blind, randomized, crossover study. After a 2-week washout period, patients in group A (n = 37) received amlodipine 10 mg and patients in group B (n = 38) received doxazosin 4 mg for 6 weeks. All patients then received reduced-dose combination therapy (amlodipine 5 mg and doxazosin 2 mg) for 6 weeks. Subsequently, patients received 6 weeks of monotherapy with the alternate medication (group A received doxazosin 4 mg and group B received amlodipine 10 mg). During both monotherapy periods, doxazosin and amlodipine significantly reduced systolic and diastolic BP (P < .001 v baseline). BP further decreased with combination therapy (P < .01 v monotherapy). The percentage of patients with Stage 2 hypertension who achieved a target BP of < 140/< 90 mm Hg increased from 78% with monotherapy to 94% with combination therapy. Fewer adverse effects were observed during combination therapy. It is concluded that there is an additional fall in blood pressure when reduced doses of doxazosin and amlodipine are used in combination for the treatment of hypertension, suggesting that doxazosin should be considered as an effective add-on treatment to calcium-channel blockers.     

Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients

BACKGROUND: The aim of this study is to compare the long-term effect of amlodipine and fosinopril in monotherapy or in combination on urinary albumin excretion (UAE) in hypertensive diabetic patients. METHODS: We selected 453 hypertensive patients with type 2 diabetes and microalbuminuria and randomized them to amlodipine (5 to 15 mg/day), fosinopril (10 to 30 mg/day), or amlodipine plus fosinopril (5/10 to 15/30 mg/day) for a 3-month titration period. The nonresponder patients or those complaining of side effects during the titration period were discontinued (n = 144); the remaining 309 patients were enrolled in the trial and treated with the same therapy for 4 years. Every 6 months, blood pressure (BP), heart rate (HR), UAE, creatinine clearance, and glycosylated hemoglobin (HbA1c) were evaluated. RESULTS: The combination therapy was more effective in reducing BP than either drug alone at any time of the study without affecting glucose homeostasis. All three treatments provided a significant decrease in UAE during the 48-month study period. However, this effect was more pronounced and became evident earlier with fosinopril than with amlodipine monotherapy (after 3 v 18 months of therapy). In addition, the combination therapy provided a greater antialbuminuric effect than the single drugs. This could be due to the greater antihypertensive effects, although other drug-specific effects cannot be excluded. The cardiovascular outcomes were similar in the amlodipine and in the fosinopril group, but they were lower in the combination group. CONCLUSIONS: These results strengthen the rationale to use a calcium-antagonist/angiotensin converting enzyme inhibitor combination in the treatment of hypertensive patients with type 2 diabetes.     

Effectiveness of add-on low-dose diuretics in combination therapy for hypertension: losartan/hydrochlorothiazide vs. candesartan/amlodipine.

In guidelines, a combination therapy of two or more antihypertensives is recommended for treatment of hypertension where monotherapy is ineffective. Although diuretics or calcium channel blockers are commonly used as add-ons to angiotensin receptor blocker (ARB), the most effective and safe combination has not been established. In this randomized 4-month study, the efficacy and safety were compared between an ARB/diuretics (losartan/hydrochlorothiazide [HCTZ]) combination and the most prescribed combination, ARB/calcium channel blocker (candesartan/amlodipine) in hypertensive patients for whom 8 mg/day of candesartan proved ineffective. After 36 patients were recruited and allocated into two groups, changes in blood pressure (BP) and laboratory values were analyzed in 31 patients: 16 patients received losartan (50 mg/day)/HCTZ (12.5 mg/day) (L/H group), and 15 patients received candesartan (8 mg/day)/amlodipine (5 mg/day) (C/A group) after 5 patients were withdrawn. After 4 months, L/H significantly (p<0.001) reduced mean systolic BP (SBP)/diastolic BP (DBP) from baseline 160/89 +/- 13/11 mmHg to 140/80 +/- 9/8 mmHg, and C/A reduced BP from 161/90 +/- 10/11 mmHg to 141/79 +/- 10/7 mmHg. The efficacy in reducing BP was similar between the two combination therapies. L/H significantly reduced serum potassium, but within the normal range, and did not increase serum uric acid or serum triglyceride. With L/H, the percentage of patients who attained the BP goal in SBP was higher in elderly patients than in younger patients. As L/H is more cost-effective than candesartan/amlodipine and has fewer adverse effects on uric acid and other metabolic parameters than diuretic monotherapy, it is concluded to be useful for the management of hypertension.     

Cardiovascular effects of combination of perindopril, candesartan, and amlodipine in hypertensive rats

The combination therapy with ACE inhibitors, angiotensin II type 1 (AT(1)) receptor antagonists, or calcium channel antagonists may exert more beneficial effects on cardiovascular diseases than monotherapy. Perindopril, candesartan cilexetil, or amlodipine alone or the combination of low doses of each agent was administered orally to stroke-prone spontaneously hypertensive rats (SHRSP) for 4 weeks to compare the hypotensive or cardiovascular effects. Although perindopril (2 mg/kg), candesartan cilexetil (2 mg/kg), or amlodipine (3 mg/kg) alone caused comparable hypotensive effects in SHRSP, monotherapy with perindopril or candesartan decreased left ventricular (LV) weight; mRNA levels for atrial natriuretic factor, skeletal alpha-actin, and collagen types I and III; and aortic weight and platelet-derived growth factor-beta receptor tyrosine phosphorylation to a greater extent than monotherapy with amlodipine. Although monotherapy with a low dose (0.2 mg/kg) of perindopril or candesartan cilexetil did not significantly reduce the LV mRNA levels and aortic platelet-derived growth factor-beta receptor phosphorylation of the SHRSP, combination therapy at such a low dose normalized these parameters more potently than the use of amlodipine (3 mg/kg) alone. Although perindopril or candesartan cilexetil alone at 0.05 mg/kg did not decrease the blood pressure of the SHRSP, such a low dose of combination therapy decreased LV weight and atrial natriuretic factor mRNA levels of the SHRSP to a greater extent than amlodipine alone or amlodipine combined with perindopril or candesartan cilexetil. Our results provide evidence that suggests the combination of an ACE inhibitor and an AT(1) receptor antagonist may be more effective in the treatment of cardiac and vascular diseases than the combination of a calcium channel blocker with an ACE inhibitor or an AT(1) receptor antagonist or monotherapy with each agent.