Initial combination therapy compared with monotherapy in diabetic hypertensive patients

Subgroup analyses were performed for the diabetic and nondiabetic cohorts from 3 randomized clinical trials that had evaluated the systolic blood pressure (SBP)-lowering efficacy and tolerability of an angiotensin receptor blocker, valsartan, alone or in combination with hydrochlorothiazide to determine when and how to initiate combination therapy in hypertensive patients with diabetes. Blood pressure reductions achieved with monotherapy were compared with combination therapy in the diabetic and nondiabetic cohorts. In addition, multivariate models were developed to predict the likelihood of the goal SBP of < 130 mm Hg being reached in a diabetic patient with monotherapy or combination therapy across the range of baseline SBP values. In 2 of the 3 trials, comparable reductions in SBP were seen in the diabetic and nondiabetic cohorts. In all 3 studies, however, combination therapy provided greater blood pressure-lowering efficacy than monotherapy. The probability of achieving goal SBP was greater for diabetic patients started on combination therapy compared with monotherapy.     

缬沙坦与氨氯地平联合用药和缬沙坦单药治疗高血压合并2型糖尿病的对照试验

目的 评价缬沙坦与氨氯地平联合用药和缬沙坦单药治疗高血压合并2型糖尿病患者的有效性和安全性.方法 本研究为随机、双盲、平行对照研究.125例高血压合并2型糖尿病患者经2周洗脱期后,给予4周缬沙坦（80 mg/d）单药治疗,89例平均坐位舒张压（SeDBP）仍≥90 mm Hg的患者随机分为缬沙坦（80 mg/d）和氨氯地平（5 mg/d）联合用药治疗组及缬沙坦（80 mg/d）单药治疗组,共随机双盲治疗8周,以SeDBP下降差值和尿白蛋白排泄率（UAER）下降值作为主要疗效指标.54例患者（联合用药组28例,单药组26例）完成了24h动态血压监测,并作为降压疗效的评价指标.结果 随机、双盲治疗8周末,联合用药组SeDBP下降值为（13.7±5.8）mm Hg,达目的血压占65.9％;单药治疗组SeDBP下降值为（7.7±6.9）mm Hg,达目的血压占37.8％,两组组间比较差异有统计学意义（P＜0.01）.联合用药组尿白蛋白排泄率（UAER）为（7.15±2.13）μg/min,单药治疗组尿白蛋白排泄率（UAER）为（8.76±3.01）μg/min（P＜0.05）.24h动态血压监测结果,联合用药组和单药治疗组舒张压/收缩压（DBP/SBP）的谷/峰比率（T/P）分别为83.1％/76.0％和85.8％/79.5％（P＜0.05）.联合用药组与单药治疗组的不良反应发生率分别为5.2％和 10.7％（P＜0.01）.结论 缬沙坦与氨氯地平联合用药治疗高血压合并2型糖尿病的降压疗效明显优于缬沙坦单药治疗,且具有明显的肾脏保护作用.     

Efficacy of a fixed-dose combination of trandolapril-verapamil in obese hypertensive patients resistant to monotherapy

This paper sought to determine if the fixed-dose combination of trandolapril and verapamil is effective in the treatment of hypertensive obese patients resistant to monotherapy. Thirty-six hypertensive obese patients uncontrolled by monotherapy were given the combination of trandolapril-verapamil (2/180 mg) for 12 weeks. Before and after taking the drug, they self-measured their blood pressure. Patients experienced a significant reduction of blood pressure (from 178 +/- 18/100 +/- 12 mm Hg to 135 +/- 14/76 +/- 7 mm Hg, p < 0.001). Eighty percent of patients reached therapeutic goals; one patient suffered from headaches and one had constipation. it was determined that the combination of trandolapril-verapamil is effective and safe for the management of hypertension in obese patients uncontrolled by monotherapy.     

The efficacy and safety of fixed-dose combination of amlodipine/benazepril in Chinese essential hypertensive patients not adequately controlled with benazepril monotherapy: a multicenter,randomized, double-blind,double-dummy,parallel-group clinical trial

This double-blind, double-dummy clinical trial evaluated the efficacy and safety of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese hypertensive patients not adequately controlled with benazepril. Of 442 patients who received treatment with benazepril 10?mg for 4 weeks, 341 patients failed to achieve to diastolic blood pressure (DBP) <90?mmHg. These non-responders were randomized to receive amlodipine/benazepril 2.5/10?mg, or amlodipine/benazepril 5/10?mg, or benazepril 10?mg for 8 weeks. BP reductions with amodipinel/benazepril 2.5/10?mg (15.2/11.8?mmHg) or amlodipine/benazepril 5/10?mg (15.4/12.4?mmHg) were significantly greater than that with benazepril 10?mg (9.88/9.46?mmHg) at study end (p?p?0.01, combination versus benazepril). Three groups were generally well tolerated. Our study indicated that amlodipine/benazepril fixed-dose combination offered significant additional BP reductions and BP control rate compared with the continuation of benazepril monotherapy. No significant differences were observed in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10?mg and amlodipine/benazepril 5/10?mg.     

Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting

BACKGROUND: Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension. METHODS: Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or = 90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy. RESULTS: In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%) experienced some improvement in edema compared with baseline levels. CONCLUSIONS: Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.     

LAM add-on ADV combination therapy or ETV monotherapy for CHB patients with suboptimal response to ADV

Introduction. Among the available nucleos(t)ide analogues adefovir dipivoxil (ADV) is relatively cheap and widely used in rural area in China. However, there are insufficient data on recommendation for patients with suboptimal response to ADV after 48 weeks of treatment in order to reduce the resistance rate in the long term. The aim of this study was to compare the efficacy and safety of LAM add-on combination therapy versus ETV monotherapy for patients with suboptimal response to ADV.Material and methods. 136 patients with suboptimal response to ADV were randomly assigned to the add-on LAM with ADV combination therapy (68 patients) group and the ETV monotherapy (68 patients) group. Patients in the add-on group were prescribed 100 mg LAM and 10 mg ADV per day, while the monotherapy group received 0.5 mg ETV per day for 48 weeks. Tests for liver and kidney function, HBV serum markers, HBV DNA load, were performed every 3 months.Results. The mean patient age in LAM add-on group and ETV monotherapy was 38.59 ± 7.65 and 37.56 ± 8.67 years respectively. The HBV DNA undetectable rate in the LAM add-on group and the ETV group were not significant difference at week 4, 12 and 24 (P > 0.05). However, the HBV undetectable rate in the ETV group was higher than that in the LAM add-on group at week 36 and 48 (P = 0.043 for week 36 and P = 0.038 for week 48). There was no significant difference both for HBeAg loss and HBeAg seroconversion between two groups (P > 0.05) at 48 weeks. Meanwhile, our study also demonstrated that the mean eGFR levels in LAM add-on group was decreased from 99.6 ± 8.71 at baseline to 86.4 ± 9.83 at the end of 48 weeks, which was significantly higher than that in the ETV monotherapy group (P < 0.05). 8.8% of patients in LAM add-on group experienced eGFR reduction by 20-30% from baseline at 48 weeks. No patients developed hyposphosphatemia in our study.Conclusion. Our study clearly showed that switch to ETV monotherapy was the more effective and more safe than that of LAM add-on combination therapy for patients with suboptimal response to ADV.     

Effect of fixed-dose ACE-inhibitor/calcium channel blocker combination therapy vs. ACE-inhibitor monotherapy on arterial compliance in hypertensive patients with type 2 diabetes

Assessment of vascular compliance may be a useful measurement of the clinical effects of antihypertensive treatment. Both angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are known to improve vascular elasticity. A study was performed to test the hypothesis that combined therapy with an ACE inhibitor and a calcium channel blocker would have additive benefits on vascular compliance at similar levels of blood pressure (BP), as compared with monotherapy with an ACE inhibitor. This 12-week, double-blind study was a substudy of a larger clinical hypertension study conducted in patients with hypertension and type 2 diabetes. Subjects (N = 20) were randomized to either a fixed-dose combination of amlodipine besylate/benazepril HCl or to enalapril monotherapy. BP, heart rate, large- and small-vessel compliance, systemic vascular resistance, and urinary microalbumin excretion were assessed at baseline and after treatment. Both treatments were similarly effective in lowering BP, reducing systemic vascular resistance, and decreasing urinary microalbumin excretion. Improvement in large-vessel compliance was significantly greater among subjects who received ACE-inhibitor/calcium channel blocker combination therapy (52%) as compared with those who received ACE-inhibitor monotherapy (32%; p < 0.05). No significant change in small-vessel compliance was observed with either treatment. Greater improvement in large-vessel compliance with combination therapy was independent of BP lowering.     

Meta-analysis of monotherapy versus combination therapy for pulmonary arterial hypertension

Previous studies comparing combination therapy (CT) of pulmonary vasodilators to monotherapy (MT) in patients with pulmonary arterial hypertension (PAH) report conflicting results as to whether CT is more efficacious than MT. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials comparing CT to MT for patients with PAH. Data were pooled using the DerSimonian-Laird random-effects model. Six randomized controlled trials including 729 patients met our inclusion criteria. Follow-up ranged from 12 to 16 weeks. Compared to MT, CT resulted in a modest increase in 6-minute walk distance at the end of follow-up (weighted mean difference 25.2 m, 95% confidence interval [CI] 13.3 to 37.2). CT did not decrease mortality (risk ratio [RR] 0.42, 95% CI 0.08 to 2.25), admissions for worsening PAH (RR 0.72, 95% CI 0.36 to 1.44), or escalation of therapy (RR 0.36, 95% CI 0.09 to 1.39) and did not improve New York Heart Association functional class (RR 1.32, 95% CI 0.38 to 4.5) compared to MT. Incidence of study-drug discontinuation was similar between groups (RR 0.89, 95% CI 0.53 to 1.48). CT did not decrease the combined end point of mortality, admission for worsening PAH, lung transplantation, or escalation of PAH therapy (RR 0.42, 95% CI 0.17 to 1.04). In conclusion, this meta-analysis suggests that in PAH CT does not offer an advantage over MT apart from modestly increasing exercise capacity. However, given the paucity of good-quality data, more studies are required to define the efficacy of CT in this population before establishing final guidelines.     

A candesartan cilexetil/hydrochlorothiazide combination tablet provides effective blood pressure control in hypertensive patients inadequately controlled on monotherapy

In this double-blind, placebo-controlled, randomised, parallel-group study, a combination tablet of candesartan cilexetil/hydrochlorothiazide (HCTZ), 16/12.5 mg once daily, reduced sitting diastolic blood pressure (DBP) significantly more (p = 0.037) than candesartan cilexetil/placebo, 16 mg once daily, in patients with mild to moderate primary hypertension (n = 328) who had not reached target blood pressure with candesartan cilexetil, 16 mg once daily. At the end of the 8-week double-blind treatment period, the adjusted mean reductions in sitting DBP, 24 h post dose, were 7.5 mm Hg in the candesartan cilexetil/HCTZ treatment group and 5.5 mm Hg in the candesartan cilexetil/placebo treatment group, corresponding to an adjusted mean difference between treatments of 2.0 mm Hg in favour of candesartan cilexetil/HCTZ (95% CI 0.1-3.8 mm Hg, p = 0.037). The adjusted mean reductions in sitting systolic blood pressure, 24 h post dose, were 12.0 mm Hg and 7.5 mm Hg, respectively, corresponding to an adjusted mean difference between treatments of 4.5 mm Hg (95% CI 1.1-8.0, p = 0.01). Consistent with the placebo-like tolerability of candesartan cilexetil reported in other studies, both treatments were very well tolerated, with a similar pattern and low frequency of adverse events in both treatment groups.     

Antibiotic streamlining from combination therapy to monotherapy utilizing an interdisciplinary approach

Streamlining of antibiotic therapy from a more complex to a less complex regimen should reduce hospital costs. Utilizing the expertise of an infectious disease physician and clinical pharmacists, an antibiotic-streamlining program was implemented by (1) daily collection of data on patients receiving two or more parenteral antibiotics, (2) formulation of recommendations of cost-effective alternative therapy when clinically appropriate, (3) oral and/or written communication of the reasons for the recommendation to the patient's physician, (4) follow-up monitoring, and (5) determination of the cost savings by subtracting the actual cost of antibiotic therapy (including labor and supplies) from the cost of the initial regimen if it had been continued without alteration. Streamlining recommendations were made in 340 of 625 patients who were reviewed during the initial seven months. Cases that necessitated streamlining recommendations decreased from 98.6% during the first month to 54.4% during the seventh month, reflecting the educational impact of the program on prescribing habits. Recommendations were followed in 82.6% of the cases, of which 97.2% completed therapy with the streamlined regimen. The projected annual savings of the program was +107,637.     

Comparison of monotherapy versus combination antihypertensive therapy in elderly patients with essential hypertension

Authors sought to compare the efficacy of monotherapy versus combination antihypertensive therapy in elderly patients. Patients in this study, aged 65 to 85 years, were divided into 4 groups and entered an 8-week treatment period. First group: 22 patients, amlodipine 5 mg/d increasing to 10 mg; second: 20 patients, eprosartan 600 mg/d increasing to 600 mg twice a day; third: 21 patients, amlodipine 5 mg/d and indapamide 2.5 mg/d, increasing amlodipine to 10 mg/d; fourth: 23 patients, imidapril 10 mg/d and indapamide 2.5 mg/d, imidapril doubled to 20 mg/d. A greater drop in systolic and in diastolic blood pressure was obtained by combination of amlodipine and indapamide compared with amlodipine or eprosartan monotherapy. Imidapril and indapamide showed similar efficacy compared with eprosartan monotherapy but not with amlodipine monotherapy. Amlodipine and indapamide appeared more effective than imidapril and indapamide in diastolic blood pressure. Combination treatment with amlodipine and indapamide or imidapril and indapamide effectively reduces blood pressure in elderly patients with essential hypertension.     

Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients

 Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one patients with hematological malignancies (55%) or solid tumors (45%), neutropenia <500/μl, and fever <38.5  °C were randomly assigned to either meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15 mg/kg/day) intravenously. Meropenem (n=34) and ceftazidime/amikacin (n=37) were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p<0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29% versus 25%), whereas all gram-negative bacteremias responded except for one in the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72 h. One patient in each group died of gram-positive sepsis resistant to study medication. No significant side effects occurred in any regimen. This study suggests that meropenem monotherapy might be as effective as combination therapy with ceftazidime and amikacin for the empirical treatment of febrile neutropenic patients. Received: 13 June 1997 / Accepted in revised form: 5 December 1997     

氯沙坦和苯那普利联合治疗肾性高血压的临床研究

目的观察氯沙坦和苯那普利联合治疗肾性高血压的疗效。方法将55例伴有高血压和稳定肾功能不全的慢性肾炎患者随机分三组，分别用氯沙坦(50mg／d)、苯那普利(10mg／d)和氯沙坦(50mg／d)加苯那普利(10mg／d)共治疗24周。单独用药组治疗12周后，若血压≤130／80mmHg(1mmHg=0．133kPa)，继续单独用药治疗12周;若血压＞130／80mmHg，改为联合用药治疗12周。观察血压、尿蛋白、血肌酐、血尿酸的变化及药物的不良反应。结果联合用药组血压控制率比单独用药组高(P＜0．01)。三种药物均有降尿蛋白作用。与治疗前比较，联合用药组第12周后血肌酐有明显下降(P＜0．05)。联合用药及单用氯沙坦均有降尿酸作用。单独用药血压未达标病例再联合用药后，血压、尿蛋白、血肌酐和血尿酸均有明显下降(P＜0．05，P＜0．01)，且尿蛋白和血肌酐的下降幅度比血压达标病例继续单独用药更显著(P＜0．05，P＜0．01)。联合用药的不良反应与单独用药相比没有明显增加。结论氯沙坦和苯那普利联合治疗伴有高血压和稳定肾功能不全的慢性肾炎，较单独用药更有效地控制血压、减少蛋白尿、降低血肌酐和血尿酸，具有良好的安全性和耐受性。     

Efficacy and tolerability of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients not adequately controlled with valsartan monotherapy

This randomized, double-blind study evaluated efficacy of a single-pill combination of amlodipine/valsartan (Aml/Val) in Asian patients with hypertension not responding to Val 80 mg. Patients with mean sitting diastolic blood pressure (DBP) ≥90-≤110 mmHg were randomized to Aml/Val 5/80, Val 80, or Val 160 mg for 8 weeks. At week-8 endpoint, significantly greater reductions in BP were seen with Aml/Val 5/80 mg than valsartan monotherapies (p < 0.0001). The BP control was greater with Aml/Val 5/80 (70.5%) than Val (44.1-58.6%) monotherapies. The combination was well tolerated. In conclusion, single-pill combination with Aml/Val provided significant additional BP reduction and control in hypertensive patients not responding to Val 80 mg.