Antiischemic and metabolic effects of nebivolol and metaprolol CR/XL (betalok ZOK) in patients with postinfarction heart dysfunction

The purpose of the study was to evaluate anti-ischemic and metabolic effects of the cardioselective beta-adrenoblockers nebivolol and retarded metoprolol-metaprolol CR/XL (betalok ZOK) in patients with postinfarction heart dysfunction, associated with type II diabetes mellitus (DM). 40 patients with coronary heart disease (CHD), functional class (FC) II-III exertional angina, postinfarction left ventricular (LV) dysfunction, and NYHA FC II heart failure, associated with type II DM, were randomized into 2 groups. The 20 patients of the 1st group were administered nebivolol in a dose of 1.25 to 5 mg per day, the 20 patients of the 2nd group - betalok ZOK in a dose of 12.5 to 100 mg per day. The course therapy lasted 8 weeks. The effects of the treatment were evaluated using paired veloergometry, echoCG, and lipid spectrum analysis. The study found that nebivolol in a mean dose of 4.2 +/- 0.3 mg per day and betalok ZOK in a dose of 46.5 +/- 6.2 mg per day reduced the frequency and severety of angina attacks (by 73.8% and 67.8%, respectively) and daily nitroglycerine uptake (by 78.6% and 69.1%, respectively), and increased activity tolerance (by 7.9% and 25.3%, respectively). None of the preparations displayed any adverse effects on carbohydrate exchange and blood lipid spectrum. Nebivolol, unlike betalok ZOK, significantly (p = 0.02) reduced triglyceride blood level by 29%. Thus, the new generation cardioselective beta1-adrenoblockers nebivolol and metoprolol CR/XL (betalok ZOK) provide anti-ischemic and metabolic effects in patients with CHD and postinfarction LV dysfunction, associated with type 2 diabetes mellitus. Nebivolol is preferable as far as blood lipid spectrum is concerned.     

不同时间服用琥珀酸美托洛尔缓释片对肾性高血压患者血压昼夜节律的影响

目的观察不同时间服用琥珀酸美托洛尔缓释片(商品名:倍他乐克)对肾性高血压患者血压昼夜节律的影响。方法选择60例肾性高血压患者,按随机数字表法分为A、B两组,分别于晚上7时和早晨7时服用琥珀酸美托洛尔缓释片47.5 mg/d。用药6周后动态血压监测(Ambulatory Blood Pressure Monitoring,ABPM),比较两组血压昼夜节律的变化。结果治疗6周后,夜间平均收缩压/平均舒张压(nSBP/nDBP)A组较B组下降明显(P<0.05);日间平均收缩压/平均舒张压(dSBP/dDBP)B组较A组下降明显(P<0.05)。用药前后两组夜间血压下降程度自身比较,差异均有统计学意义(P<0.05);A组用药后夜间血压下降程度显著大于B组(P<0.05)。A组比B组夜间血压下降有效率更高,差异有统计学意义(P<0.05)。结论对于肾性高血压,琥珀酸美托洛尔缓释片晚上服用可以更好改变血压昼夜节律,达到保护靶器官的目的 。     

Atenolol and chlorthalidone therapy for hypertension: a double-blind comparison

In a randomized, double-blind, parallel-group study of 31 patients with mild to moderate hypertension, we compared a placebo regimen with a regimen of atenolol and chlorthalidone (Tenoretic). The study, which lasted seven weeks, began with a single-blind two-week placebo lead-in period, followed by a four-week double-blind treatment phase, and concluded with a one-week single-blind placebo washout period. Of 24 patients included in the analysis of efficacy, seven received one Tenoretic 50 tablet per day (atenolol, 50 mg; chlorthalidone, 25 mg), nine received one Tenoretic 100 tablet per day (atenolol, 100 mg; chlorthalidone, 25 mg), and eight received placebo. Supine systolic/diastolic blood pressure (mean +/- SD) decreased from 154 +/- 15.2/102 +/- 4.6 mm Hg during the baseline period to 128 +/- 8.5/85 +/- 4.0 mm Hg during treatment in the group receiving Tenoretic 100, from 153 +/- 12.6/104 +/- 5.4 mm Hg to 137 +/- 4.5/91 +/- 4.4 mm Hg in the group receiving Tenoretic 50, and from 150 +/- 11.9/101 +/- 1.6 mm Hg to 145 +/- 11.6/93 +/- 5.1 mm Hg in the group receiving placebo. Reductions in systolic and diastolic blood pressures in the active treatment groups were significantly greater than the pressure reductions in the group receiving placebo (P less than .05 to .1). The combination of atenolol and chlorthalidone was well tolerated, and in no case was treatment discontinued because of side effects. This study showed that one tablet per day of either Tenoretic 50 or Tenoretic 100 is effective and well tolerated in the treatment of mild to moderate hypertension.     

A 24-week dose-titration study of the angiotensin-converting enzyme inhibitor imidapril in the treatment of mild-to-moderate essential hypertension in the elderly

This multicentre, randomized, double-blind study compared the anti-hypertensive efficacy and safety of oral once-daily imidapril 5-20 mg and hydrochlorothiazide 12.5-50 mg in elderly patients with mild-to-moderate essential hypertension. After 24 weeks of treatment, there was a significant reduction in mean sitting diastolic blood pressure from 102.5 mmHg to 87.2 mmHg in the imidapril group (n = 226) and from 102.7 mmHg to 87.4 mmHg in the hydrochlorothiazide group (n = 123) (intent-to-treat population). There were corresponding reductions in sitting systolic blood pressure and standing blood pressure. At least one adverse event was reported by 46% of patients in the imidapril group and 53% of patients in the hydrochlorothiazide group. Imidapril 5-20 mg is as effective and well tolerated as hydrochlorothiazide in the treatment of mild-to-moderate hypertension in elderly patients.     

A placebo-controlled comparison of the efficacy and tolerability of candesartan cilexetil, 8 mg, and losartan, 50 mg, as monotherapy in patients with essential hypertension, using 36-h ambulatory blood pressure monitoring

This double-blind, randomised, controlled study compared the efficacy of candesartan cilexetil 8 mg (n = 87) and losartan 50 mg (n = 89), once daily for 6 weeks, relative to placebo (n = 80) in patients with mild-to-moderate essential hypertension (diastolic blood pressure (DBP): 95-115 mmHg). Ambulatory BP measurements were done every 15 min over 36 h. At the end of the 6-week treatment, the mean change in DBP between the baseline and the 0-24-h period after the last dose of study medication was greater in patients receiving candesartan cilexetil 8 mg (-7.3 mmHg +/- 6.9 mmHg) compared with losartan 50 mg (-5.1 mmHg +/- 4.9 mmHg) (p < 0.05) or placebo (0.3 mmHg +/- 6.5 mmHg) (p < 0.001). The mean change in systolic BP (SBP) during this time was greater in patients receiving candesartan cilexetil 8 mg (-10.8 mmHg +/- 11.3 mmHg), or losartan 50 mg (-8.8 mmHg +/- 8.9 mmHg) than placebo (1.2 mmHg +/- 9.9 mmHg) (p < 0.001). Candesartan cilexetil 8 mg was associated with a greater reduction in DBP and SBP, relative to placebo, when compared with losartan 50 mg, during both daytime and night-time, and between 12 and 24 h after dosing (p < 0.001). Both active treatments were well tolerated. In patients with mild-to-moderate essential hypertension, candesartan cilexetil 8 mg therefore had greater, more consistent antihypertensive efficacy throughout the day and the night, and long-lasting efficacy after the last dose, compared with losartan 50 mg. This greater efficacy is maintained with an excellent tolerability associated with members of the angiotensin Il type 1-receptor blocker class.     

Olmesartan compared with other angiotensin II receptor antagonists: Head-to-head trials

Background: Drugs that block the renin-angiotensin system represent one of the most significant therapeutic interventions available for the treatment of hypertension. The angiotensin II receptor antagonists (AIIRAs), also known as sartans, are one such class of drugs that block the effects of angiotensin II by antagonizing the angiotensin II type 1 receptor. Olmesartan is the newest member of this class.Objective: The present article reviews 3 head-to-head trials directly comparing the antihypertensive efficacy of olmesartan with that of 4 other AURAS, at recommended maintenance doses, already in clinical use for the treatment of hypertension.Results: In the first study, olmesartan 10 mg/d was compared with losartan 50 mg/d in 316 patients with mild to moderate hypertension (mean baseline diastolic blood pressure [DBP], 95–114 mm Hg). Dosage was doubled at week 4 and hydrochlorothiazide was added at week 12 if blood pressure response was inadequate. Olmesartan was significantly more effective than losartan with respect to the reduction in blood pressure at weeks 2, 4, and 12, and to the responder rate at weeks 2 and 4 (with the starting dose of the respective drug). In a second study, olmesartan 20 mg/d was shown to be significantly more effective than losartan 50 mg/d, valsartan 80 mg/d, and irbesartan 150 mg/d in 588 patients with mild to moderate hypertension (mean sitting baseline DBP, 100–115 mm Hg) (P ⩽ 0.05). At week 2, the reduction in blood pressure observed with olmesartan was significantly greater than that of the comparator treatments (P ⩽ 0.05). The superiority of olmesartan was maintained at week 8. The third study involved 643 evaluable patients with moderate to severe hypertension (mean DBP, 100–120 mm Hg; mean systolic blood pressure, >150 mm Hg). Olmesartan 20 mg/d was more effective than candesartan 8 mg/d in lowering 24-hour blood pressure at week 8 (P ⩽ 0.05). Most of this treatment effect was evident after only 1 or 2 weeks, with greater reductions in blood pressure compared with candesartan.Conclusions: These data indicate that, at the doses studied, olmesartan is more effective than other AIIRAs tested at their recommended doses, in terms of reduction of cuff or 24-hour ambulatory blood pressure, in patients with essential hypertension. These differences in blood pressure reduction between these agents may be clinically relevant and have important long-term implications. Additional studies will further define the role of olmesartan in the management of cardiovascular diseases, such as atherosclerosis.     

A double-blind ambulatory blood pressure monitoring study of the efficacy and tolerability of once-daily telmisartan 40 mg in comparison with losartan 50 mg in the treatment of mild-to-moderate hypertension in Taiwanese patients

Ambulatory blood pressure monitoring (ABPM) was used to compare the efficacy and tolerability of once-daily telmisartan 40 mg and once-daily losartan 50 mg in Taiwanese patients with mild-to-moderate essential hypertension in a randomised, double-blind, double-dummy, parallel-group study. The initial 2-week placebo run-in phase was followed by randomisation to treatment with telmisartan 40 mg (n = 31) or losartan 50 mg (n = 30) for 6 weeks. The reduction in 18- to 24-h mean (SE) ambulatory diastolic blood pressure (DBP) from baseline was significantly greater with telmisartan 40 mg (-12.1 +/- 1.6 mmHg, p = 0.036) than with losartan 50 mg (-7.0 +/- 1.8 mmHg). The reduction in 18- to 24-h mean (SE) ambulatory systolic blood pressure (SBP) from baseline was also greater with telmisartan 40 mg (-16.0 +/- 2.4 mmHg) than with losartan 50 mg (-11.8 +/- 2.7 mmHg), but did not achieve statistical significance. Telmisartan was well tolerated; no serious adverse events occurred.     

A multicenter,randomized, double-blind,placebo-controlled, 8-week trial of the efficacy and tolerability of once-daily losartan 100 mg/hydrochlorothiazide 25 mg and losartan 50 mg/hydrochlorothiazide 12.5 mg in the treatment of moderate-to-severe essential hypertension

BACKGROUND: Many patients with moderate-to-severe hypertension require multiple drug therapy to achieve blood-pressure goals. Fixed-dose combination therapy with losartan and hydrochlorothiazide may be useful in this population. OBJECTIVE: This study was conducted to obtain additional data on the antihypertensive efficacy and tolerability of once-daily, fixed-dose combinations of losartan and hydrochlorothiazide. METHODS: This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Patients > or = 21 years of age with moderate-to-severe essential hypertension, defined as a mean trough sitting diastolic blood pressure (SiDBP) of 105 to 115 mm Hg, were randomly assigned in a 2:2:1 ratio to receive losartan 100 mg/hydrochlorothiazide 25 mg (L100/25), losartan 50 mg/hydrochlorothiazide 12.5 mg (L50/12.5), or placebo (PBO) once daily for 8 weeks. The primary efficacy measurement was the mean change from baseline in trough SiDBP in the L100/25 versus L50/12.5 treatment groups. Responders were defined as patients with mean trough SiDBP <90 mm Hg or a > or = 10-mm Hg decrease in mean trough SiDBP. RESULTS: A total of 446 patients were randomly assigned to receive L100/25 (n = 173), L50/12.5 (n = 184), or PBO (n = 89). At week 8, mean trough SiDBP was significantly lower than at baseline in the L100/25 (-17.5 mm Hg), L50/12.5 (-15.2 mm Hg), and PBO groups (-8.5 mm Hg) (all P < 0.001). The difference between the active-treatment groups was statistically significant (-2.2 mm Hg; 95% Cl, range -3.8 to -0.6) (P = 0.006), as was the difference between the L100/25 and PBO groups (-9.0 mm Hg; 95% CI, range -I1.0 to -7.0) (P < 0.001) and the L50/12.5 and PBO groups (-6.7 mm Hg; 95% CI, range -8.7 to -4.8) (P < 0.001). At week 8, the percentages of responders were 86.7% (144 of 166), 78.9% (142 of 180), and 50.0% (42 of 84) in the L100/25, L50/12.5, and PBO groups, respectively. The incidence of adverse experiences (AEs) was 34.7% (60 of 173) in the L100/25 group, 23.9% (44 of 184) in the L50/12.5 group, and 32.6% (29 of 89) in the PBO group. The incidence of drug-related AEs was similar among the treatment groups (L100/25, 7.5% [13 of 173]; L50/12.5, 7.1% [13 of 184]; and PBO, 11.2% [10 of 89]). CONCLUSIONS: This study demonstrates the antihypertensive efficacy and tolerability of the once-daily, fixed-dose combination L50/12.5 in patients with moderate-to-severe essential hypertension. In this study, L100/25 provided additional anti-hypertensive efficacy beyond that of L50/12.5 (and both were more efficacious than PBO). Approximately 4 of 5 patients (78.9%) treated with L50/12.5 responded to therapy, as did nearly 9 of 10 patients (86.7%) treated with L100/25. The tolerability profiles of L50/12.5 and L100/25 were similar to that of PBO.     

Use of phisiotens for the treatment of arterial hypertension in elderly patients

AIM: To study effectiveness and safety of physiotens in elderly patients with essential hypertension (degree 1-2). MATERIAL AND METHODS: The trial enrolled 10 patients (6 males and 4 females) at the age of 60 to 75 years (mean age 66.4 +/- 3.7 years) with untreated or ineffectively treated essential hypertension (degree I-II by WHO classification). The disease stood for 17 +/- 5.3 years. Physiotens was given for 2 weeks in a single daily dose 0.2-0.4 mg. 24-h blood pressure monitoring, standard neuropsychological examination, echoCG, assessment of quality of life (Visual Analog Scale, Disability Scale) were performed before and after the treatment. RESULTS: Physiotens significantly reduced systolic and insignificantly diastolic pressure in daytime and at night; improved memory and thinking; 24 weeks of the treatment led to a decrease in left ventricular myocardium mass (by 13%, on the average) and in the thickness of left ventricular walls (by 7% on the average) as well as in life quality. CONCLUSION: Long-term physiotens treatment of elderly patients with mild and moderate hypertension provides a fall in day and night arterial pressure, regression of left ventricular myocardium mass, improves quality of life, memory and thinking.     

Comparison of hydrochlorothiazide and hydrochlorothiazide plus bevantolol in hypertension

The added hypotensive effect of bevantolol, a new cardioselective beta-blocker, was studied in 244 patients with mild to moderate essential hypertension following prior treatment with hydrochlorothiazide or placebo. After four weeks of monotherapy with 50 mg/day or 100 mg/day of hydrochlorothiazide or placebo, the mean diastolic blood pressure of the patients in these groups decreased from baseline by 8.6, 8.8, and 4.3 mmHg, respectively. During the subsequent four weeks of dual therapy with 400 mg/day of bevantolol added to the regimen, additional and uniform mean decreases of 7.5, 7.3, and 7.5 mmHg occurred, providing total mean diastolic pressure decreases from baseline of 16.1, 16.1, and 11.8 mmHg in the three groups, respectively. These diastolic pressures were significantly lower during dual therapy than during monotherapy and lower in both diuretic groups than in the placebo group during monotherapy and dual therapy (P less than 0.001). Fewer adverse reactions occurred during dual therapy than during monotherapy. The addition of bevantolol to a thiazide diuretic regimen provided safe and significantly better control of mild to moderate hypertension than did the diuretic alone.     

Combined alpha/beta-blockade versus beta 1-selective blockade in essential hypertension in black and white patients

The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta-blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (-12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group.     

氯沙坦及氨氯地平对肾移植患者24 h尿蛋白及血、尿转化生长因子β_1的影响

目的:观察氯沙坦和氨氯地平对肾移植患者24 h尿蛋白及血、尿转化生长因子β_1的影响.方法:选择佛山市第一人民医院初次肾移植后伴轻、中度高血压(收缩压140～170 mm Hg,舒张压85～100 mm Hg, 1 mm Hg=0.133 kPa)患者40例,男23例,女17例,年龄(38.6±19.2)岁,随机数字表法分为氯沙坦组和氨氯地平组,每组20例.氯沙坦组口服氯沙坦50 mg/d治疗,氨氯地平组口服氨氯地平5 mg/d治疗,要求患者血压控制在130/80 mm Hg以下,治疗6个月后检测血压、肾功能、24 h蛋白尿与血、尿转化生长因子β_1水平.结果:40例患者均进入结果分析.患者用药后收缩压、舒张压均显著下降(P < 0.05),治疗6个月后,收缩压、舒张压均降至正常水平 (P < 0.01).治疗期间,2组血压下降值及平均动脉压比较差异无显著性意义 (P > 0.05).2组治疗总有效率比较差异无显著性意义 (P > 0.05).2组患者治疗前后血尿素氮、肌酐和血尿酸差异无显著性意义 (P > 0.05).治疗6个月后,氯沙坦组24 h尿蛋白与血、尿转化生长因子β_1水平较治疗前显著下降 (P < 0.05),氨氯地平组24 h尿蛋白与血、尿转化生长因子β_1水平无明显变化 (P > 0.05).氯沙坦组24 h尿蛋白与血、尿转化生长因子β_1水平均低于氨氯地平组 (P < 0.05).结论:氯沙坦与氨氯地平均可有效地控制肾移植患者的高血压状态,但氯沙坦可明显降低肾移植患者24 h尿蛋白与血、尿中转化生长因子β_1水平,氨氯地平的作用不明显.     

Effectiveness and safety of eprosartan on pulse pressure for the treatment of hypertensive patients

A multicentre, prospective, non-comparative open-label study was conducted to assess the effect of eprosartan, 600 mg/day, on pulse pressure (PP) in patients with hypertension (stage I or II, Joint National Committee, sixth report) treated in the primary care setting, as well as safety and compliance. The duration of treatment was 16 weeks. Eprosartan decreased PP (-13 mmHg), systolic blood pressure (SBP) (-26 mmHg), diastolic blood pressure (DBP) (-13 mmHg) and mean arterial pressure (MAP) (-17.4 mmHg) significantly (p < 0.0001). The PP/MAP ratio changed significantly from 62 to 59%, so that the reduction of PP was 3% higher than the overall decrease in MAP. Twenty adverse events, mostly gastrointestinal complaints, were recorded in 12 patients (1.9%). Compliance with treatment at the end of the study was 94%. Eprosartan was a well-tolerated and an effective drug in reducing PP, SBP and DBP below the recommended levels in patients with mild-to-moderate essential hypertension, allowing a high therapeutic compliance.     

A double-blind comparison of the efficacy and tolerability of telmisartan 40-80 mg vs. losartan 50-100 mg in Taiwanese hypertensive patients

A multicentre, randomised, double-blind, double-dummy, parallel-group, dose-titration study was conducted to determine the efficacy and tolerability of telmisartan 40-80 mg once daily compared with losartan 50-100 mg once daily in 180 Taiwanese patients with mild-to-moderate essential hypertension. After an initial 2-week placebo run-in phase, patients were randomised in a double-blind, double-dummy fashion to receive either telmisartan 40 mg or losartan 50 mg. If blood pressure control (diastolic blood pressure [DBP] <90 mmHg or > or = 10 mmHg reduction in DBP) was achieved after 4 weeks, the dose was maintained for the second 4 weeks of the active treatment phase; if not, the dose was doubled to telmisartan 80 mg or losartan 100 mg, respectively, for the second 4 weeks of double-blind treatment. Telmisartan 40-80 mg (n = 86) was as effective as losartan 50-100 mg (n = 90) in reducing trough seated DBP (11.1 vs. 8.7 mmHg, p = 0.144), and was significantly more effective than losartan in reducing trough seated systolic blood pressure (SBP) (22.1 vs. 16.5 mmHg, p = 0.032) and standing SBP (21.0 vs. 16.3 mmHg, p = 0.033). Significantly fewer patients treated with telmisartan than those treated with losartan required uptitration after 4 weeks' treatment (32.6% vs. 61.5%, p = 0.001). Both telmisartan and losartan were well tolerated.     

氯沙坦合用氢氯噻嗪治疗老年高血压的临床研究

目的探讨氯沙坦合用氢氯噻嗪治疗老年高血压的疗效及其副作用。方法对68例老年高血压患者应用氯沙坦(科素亚)50 mg每日1次;同时合用氢氯噻嗪(双氢克尿塞)12.5 mg,每日1次,均晨顿服,2周后降压疗效不满意,氯沙坦加至100 mg,每日1次,疗程共12周。观察治疗前后随测血压、血糖、血脂、血钾、血尿酸和肝肾功能。结果氯沙坦合用氢氯噻嗪降压总有效率达89.7%,疗效显著,无明显副作用。结论氯沙坦合用氢氯噻嗪治疗老年高血压安全、有效。     

Use of nebivolol in patients with mild and moderate hypertension

AIM: To evaluate the effectiveness and safety of the beta-adrenoblocker nebivolol in patients with mild and moderate essential hypertension. MATERIAL AND METHODS: The trial enrolled 20 patients. 11 of them had mild and 9 moderate arterial hypertension (mean age 47.1 +/- 9.52 years, hypertension history 6.98 +/- 2.75 years). 2-5 days after discontinuation of hypotensive drugs the examination was made including blood count, ECG, echocardiography, 24-h AP monitoring. It was repeated on days 56-60 of nebivolol therapy. Arterial pressure and heart rate were measured at the start of the treatment and 1, 3, 5 and 8 weeks later. RESULTS: Nebivolol treatment significantly reduced systolic arterial pressure in 30% and diastolic arterial pressure in 50% patients, heart rate decreased on the treatment day 7-10. On the treatment day 56-60 systolic and diastolic pressure lowered significantly in 53.3% and 66.7% patients, respectively. The analysis of changes in echocardiographic evidence found no significant shifts in volume and linear parameters. Nebivolol was well tolerated by 85% patients. Side effects included head ache, cardialgia, dizziness, weakness and nausea. CONCLUSION: Nebivolol (nebilet) is an effective hypotensive drug with mild side effects. Further studies on nebivolol effects on myocardial mass are needed.     

Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension

AIM: To compare efficacy and safety of nifedipin-retard (cordaflex-retard, Egis, Hungary) used in monotherapy and in combination with metoprolol (egilok, Egis, Hungary) in patients with arterial hypertension (AH). MATERIAL AND METHODS: The study included 20 patients with AH stage I-II (12 males, 8 females, mean age 57.3 years, mean duration of the disease 8.6 years). Nifedipin-retard was given in a daily dose 40 mg/day (20 mg twice a day) in monotherapy and 20 mg/day in combination with metoprolol which was administered 50 mg twice a day (a daily dose 100 mg/day). The control examination consisted of a physical examination, measurement of arterial pressure (AP) by Korotkov, registration of heart rate, ECG, 24-h AP monitoring, echocardiography. RESULTS: By 24-h AP monitoring, a 4-week treatment with nifedipin-retard alone resulted in lowering of systolic arterial pressure. The combined treatment produced a more pronounced fall both in systolic and diastolic pressure. Diastolic left-ventricular function improved in combined therapy. Side effects observed in nifedipin-retard monotherapy got much more weaker when this drug combined with metoprolol. CONCLUSION: Combination of nifedipin-retard with metoprolol provides better clinical response and tolerance than monotherapy with nifedipin-retard.     

Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Losartan Trial Investigators

OBJECTIVE: The goal of this multicenter, double-blind, randomized, parallel-group study was to compare the effects of losartan potassium (hereafter referred to as losartan), candesartan cilexitil (hereafter referred to as candesartan), and losartan/hydrochlorothiazide (HCTZ) in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] 95-115 mm Hg). METHODS: A total of 1161 patients were randomized in a 2:2:1 ratio to 12 weeks of treatment with losartan 50 mg QD, possibly titrated to 100 mg QD (n = 461); candesartan 8 mg QD, possibly titrated to 16 mg QD (n = 468); or losartan 50 mg QD, possibly titrated to losartan 50 mg plus HCTZ 12.5 mg QD (n = 232). At 6 weeks, the regimens of patients not reaching a goal SiDBP <90 mm Hg were titrated as described, whereas patients achieving this goal continued with low-dose monotherapy. The single primary end point at 12 weeks tested the equivalence of the 2 monotherapy regimens, predefined as a maximum between-treatment difference in the mean change from baseline trough SiDBP of 2.5 mm Hg. RESULTS: At 12 weeks, changes in SiDBP/sitting systolic blood pressure (SiSBP) of -12.4/-14.4 mm Hg with losartan 50 mg/100 mg and -13.1/-15.8 mm Hg with candesartan 8 mg/16 mg demonstrated equivalence between the 2 monotherapy regimens (95% CI for difference in SiDBP, -1.6 to 0.2). At 12 weeks, the losartan 50 mg/50 mg plus HCTZ 12.5 mg regimen had reduced SiDBP/SiSBP significantly more (-14.3/-18.0 mm Hg) than either the candesartan 8 mg/16 mg (SiDBP, P = 0.045; SiSBP, P = 0.017) or losartan 50 mg/100 mg regimen (SiDBP and SiSBP, P = 0.001). During the last 6 weeks, patients whose regimen had been titrated to losartan 50 mg plus HCTZ 12.5 mg (n = 114) showed a greater reduction in SiDBP/SiSBP (-14.5/ -18.7 mm Hg) than did those whose regimen had been titrated to either losartan 100 mg (-10.5/-12.3 mm Hg; n = 211) or candesartan 16 mg (-11.5/-13.2 mm Hg; n = 206), representing a clinically meaningful > or = 2.5-mm Hg) difference. All 3 treatments were well tolerated, with few patients experiencing drug-related adverse events (6.9% losartan 50 mg/100 mg, 7.5% candesartan 8 mg/16 mg, 3.0% losartan 50 mg/ 50 mg plus HCTZ 12.5 mg). Candesartan 8 mg/16 mg increased serum uric acid levels (0.13 mg/dL; 95% CI, 0.04 to 0.23), whereas losartan 50 mg/100 mg decreased them (-0.14 mg/dL; 95% CI, -0.24 to -0.04), and losartan 50 mg/50 mg plus HCTZ 12.5 mg left them unchanged (0.06 mg/dL; 95% CI, -0.07 to 0.20). CONCLUSIONS: Losartan 50 mg/100 mg and candesartan 8 mg/16 mg were comparable treatments in terms of blood pressure reduction. After titration, losartan 50 mg plus HCTZ 12.5 mg was superior to either candesartan 16 mg or losartan 100 mg in reducing hypertension. Losartan, but not candesartan, lowered serum uric acid levels and attenuated the expected increase in uric acid levels with HCTZ 12.5 mg.     

Propranolol-hydralazine combination in essential hypertension

The efficacy of a propranolol-hydralazine combination tablet was compared with that of each of its two components in the twice-daily treatment of mild to moderate essential hypertension (diastolic blood pressure: 100 to 125 mmHg). After a three-week, single-blind, placebo period, a 9- to 18-week, single-blind, dose-finding phase with the combination was performed. The daily doses of propranolol/hydralazine were 40 mg/25 mg, 80 mg/25 mg, 80 mg/50 mg, 120 mg/50 mg, 160 mg/50 mg, and 160 mg/100 mg. Of 83 patients, 73 (88%) had decreases in diastolic blood pressure equal to or greater than 10 mmHg. Thirty-eight (46%) patients had a diastolic blood pressure equal to or less than 90 mmHg while taking 80 mg propranolol/50 mg hydralazine or less given BID. Mean systolic and diastolic pressures were reduced by 16.8 mmHg (10.9%) and 17.6 mmHg (16.7%), respectively (P less than 0.001). A ten-week, double-blind, parallel-treatment phase followed in which patients were randomly assigned to the combination tablet or to propranolol or hydralazine. There were significantly larger increases in mean systolic (P less than 0.01) and mean diastolic (P less than 0.03) blood pressure when the components were taken alone than with the combination from the mean of the last three weekly dose-finding visits to the mean of the last four biweekly parallel-treatment visits. The changes in systolic/diastolic blood pressures were: hydralazine (n = 30), 14.43/8.62 mmHg; propranolol (n = 24), 9.87/6.09 mmHg; and the combination (n = 27), 1.47/1.53 mmHg. During the parallel-treatment phase, the proportions of patients with new complaints were: hydralazine, 16/31 (52%); propranolol, 10/25 (40%); and the combination, 11/27 (41%). In the hydralazine group, three patients had cardiovascular events (severe tachycardia, mild palpitations, and skipped heart beats) and two patients had mild anxiety; no such occurrences were noted in the propranolol or combination group. The mean change (increase) in heart rate from the end of dose-finding to the end of the double-blind period was significantly larger for patients taking hydralazine than for patients taking propranolol or the combination. Mean changes for these groups were: hydralazine, 12.4 beats/min; propranolol, 2.9 beats/min; and the combination, 1.8 beats/min (P = 0.0001). This study found the combination of propranolol plus hydralazine to be safe and more effective than either component.     

Once-daily fixed-combination irbesartan 300 mg/ hydrochlorothiazide 25 mg and circadian blood pressure profile in patients with essential hypertension

BACKGROUND: More than 60% of patients with hypertension included in morbidity and mortality trials needed >or=2 drugs to achieve a substantial, sustained reduction in blood pressure. Tolerable combinations using higher doses of antihypertensive drugs are frequently required to control blood pressure. OBJECTIVE: The goal of this study was to assess the effect of a once-daily fixed combination of irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg on the circadian blood pressure profile in patients with essential hypertension that was not controlled with full-dose single therapy or low-dose combined therapy. METHODS: Study patients were recruited consecutively from the outpatient hypertension clinics of 3 university hospitals in Spain. After a 1-week washout period, patients with a mean daytime blood pressure >135/85 mm Hg were treated with irbesartan 300 mg/HCTZ 25 mg once daily for 12 weeks. Twenty-four-hour ambulatory blood pressure monitoring was performed at the end of the washout period and during the last week of treatment. RESULTS: Fifty-seven patients with essential hypertension (28 men, 29 women) were enrolled; their mean (SD) age was 60.4 (7.2) years (range, 45-78 years). After treatment, a significant reduction in both clinic and ambulatory mean (SD) blood pressure values was observed in the whole group of 57 patients (from 146.0 [11.0] mm Hg to 123.3 [13.3] mm Hg, P < 0.001 for 24-hour systolic blood pressure [SBP]; from 89.9 [8.2] mm Hg to 76.5 [9.4] mm Hg, P < 0.001 for 24-hour diastolic blood pressure [DBP]. The mean lowering of ambulatory SBP and DBP at peak was 25.2 (14.5) mm Hg and 14.7 (9.5) mm Hg, respectively, and at trough, 22.3 (18.3) mm Hg and 12.3 (10.9) mm Hg. The trough-to-peak ratio of the group was 0.92 for SBP (0.97 in responders) and 0.84 for DBP (0.89 in responders). The smoothness index, calculated as the mean of all individual values, was 1.7 (1.0) for SBP (1.8 [0.9] in responders) and 1.3 (0.8) for DBP (1.5 [0.6] in responders). Seven side effects in 6 patients were reported. No metabolic changes were observed, and no patient discontinued the study because of treatment-related adverse effects. CONCLUSIONS: The fixed combination of irbesartan 300 mg/HCTZ 25 administered once daily produced a crude meaningful effect in reducing 24-hour blood pressure and was well tolerated. The circadian profile was preserved, as shown by trough-to-peak ratios and smoothness index values for both SBP and DBP.