Trimetazidine in geriatric patients with stable angina pectoris: the tiger study

This study aims to assess the efficacy and tolerance of the metabolic antianginal agent trimetazidine, a 3-KAT inhibitor, in 141 stable angina patients aged 65-86 years. Efficacy was assessed with exercise tests and clinical evaluation after 12 weeks of treatment. The main outcome was an increase in exercise duration by 52 +/- 92 sec (p < 0.001). Other exercise test parameters also improved, with no change in rate-pressure product. Angina attacks and short-acting nitrate consumption significantly decreased, indicating an improvement in quality of life. Two adverse events were reported (gastric pain and dyspepsia) but they were mild and transient. In conclusion, in elderly stable angina patients, trimetazidine improves exercise stress tests and angina symptoms. Because of its metabolic effect, free from any haemodynamic action, trimetazidine proved to be beneficial in elderly patients and with an excellent tolerance profile.     

曲美他嗪治疗稳定型心绞痛的疗效观察

目的：观察曲美他嗪辅助治疗稳定型心绞痛的疗效和安全性。方法：选择稳定型心绞痛患者110例,随机分为两组,对照组（52例）为常规心绞痛用药,曲美他嗪组（58例）在常规用药基础上加用曲美他嗪20mg,口服,每日3次,连续8周。结果：曲美他嗪组治疗总有效率高于对照组,差异有显著性（P〈0．05）;两组均无不良反应发生。结论：在常规药物治疗基础上加用曲美他嗪能更有效地缓解心绞痛,使运动耐量增加,且耐受性好,因此曲美他嗪是辅助治疗心绞痛安全、有效的药物。     

曲美他嗪对冠心病稳定性劳力型心绞痛患者心肌缺血的影响

目的探讨曲美他嗪对冠心病（CHD）稳定性劳力型心绞痛患者心肌缺血的影响。方法选择在1周内经2次运动试验,结果为阳性且运动持续时间变异低于10％的CHD稳定性劳力型心绞痛患者40例,在原有治疗不变的情况下,加用曲美他唪20mg,3次／d,治疗12周。治疗前后均行平板运动试验,观察用药前后下述指标的变化：①用药前后每周心绞痛发作的次数;②每周硝酸甘油片的用量;③心率及心率与收缩压的乘积;④运动诱发心绞痛发作所需的时间;⑤运动后ST段下降1mm所需的时间;⑥运动持续时间;⑦总工作量。结果曲美他嗪应用12周后,患者每周心绞痛发作次数及硝酸甘油片的用量明显下降（P〈0．05）,而对心率及心率与收缩压的乘积的影响无统计学意义（P〉0．05）。与试验前相比,运动耐量和总工作量显著提高（P〈0．01）,至心绞痛发作的时间及ST段下降1mm所需的时间均明显延长（P〈0．01）。不良反应较少。结论曲美他嗪能增加CHD稳定性劳力型心绞痛患者的运动耐量,改善运动诱发心绞痛的心肌缺血,且安全有效,易于耐受。     

曲美他嗪在稳定型心绞痛治疗中的临床应用研究

目的评价万爽力治疗稳定型心绞痛的疗效。方法将我院67例符合临床诊断标准的稳定型心绞痛患者随机分为对照组34例和治疗组33例。对照组患者给予硝酸酯类、β受体阻滞剂、抗凝剂及阿司匹林等基础治疗,治疗组在对照组治疗基础上加用曲美他嗪,疗程均为24周,治疗前、后检查心电图,记录心绞痛发作次数及每次心绞痛发作的平均时间以及心率、血压的变化。结果两组患者临床疗效间差异有显著性意义(P<0.05),治疗组患者治疗前、后心绞痛发作次数、持续时间及对照组患者治疗前、后心绞痛发作次数、持续时间差异均有显著性意义(P<0.05)。两组患者治疗后心绞痛发作次数、持续时间差异亦均有显著性意义(P<0.05)。曲美他嗪对心率、血压无影响。结论曲美他嗪治疗稳定型心绞痛疗效确切,能明显减少心绞痛的发作。     

曲美他嗪治疗不稳定型心绞痛的疗效观察

目的　观察在常规治疗基础上加用曲美他嗪治疗不稳定型心绞痛的疗效。方法　 10 3例确诊为不稳定型心绞痛的患者被随机分为两组 ,常规治疗组 5 1例 ,接受硝酸酯类、钙离子阻滞剂、血管紧张素转换酶抑制剂、β受体阻滞剂和抗血小板药物治疗。曲美他嗪组 5 2例 ,在常规治疗基础上加用曲美他嗪。两组治疗时间均为 (2 8± 2 )天。观察两组症状、心率、血压、动态心电图的变化及副作用。结果　与常规治疗组比较 ,曲美他嗪组的疗效更好 ,差异有统计学意义 (P <0 .0 1) ;曲美他嗪对心率、血压和率压乘积无影响 ;曲美他嗪组缺血发作次数、ST段最大下降幅度、总缺血时间的减少更为明显 ,差异均有统计学意义 (均P <0 .0 1)。结论　在常规治疗基础上加用曲美他嗪能更有效地改善不稳定型心绞痛症状 ,明显减少缺血发作次数、ST段最大下降幅度和总缺血时间。对血流动力学无影响。不良反应轻。是安全、有效、更完善的治疗方案     

曲美他嗪对心绞痛患者50例临床疗效观察

目的：观察曲美他嗪[1-（2,3,4-三甲基苯唑）哌嗪二氢盐酸盐]治疗心绞痛的临床疗效。方法：观察50例心绞痛患者采用曲美他嗪治疗前后的心绞痛发作次数、硝酸甘油消耗量、运动试验结果、静息心电图、心率及血压。结果：曲美他嗪治疗后心绞痛患者的心绞痛发作次数、硝酸甘油消耗量、总运动时间、静息心电图较治疗前有明显改善（P〈0．01）,心率及血压无明显变化。结论：曲美他嗪可改善接受常规治疗心绞痛患者的临床表现。     

A randomized, placebo-controlled study of the effects of telcagepant on exercise time in patients with stable angina

Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being evaluated for acute migraine treatment. CGRP is a potent vasodilator that is elevated after myocardial infarction, and it delays ischemia during treadmill exercise. We tested the hypothesis that CGRP receptor antagonism does not reduce treadmill exercise time (TET). The effects of supratherapeutic doses of telcagepant on TET were assessed in a double-blind, randomized, placebo-controlled, two-period, crossover study in patients with stable angina and reproducible exercise-induced angina. Patients received telcagepant (600 mg, n = 46; and 900 mg, n = 14) or placebo and performed treadmill exercise at T(max) (2.5 h after the dose). The hypothesis that telcagepant does not reduce TET was supported if the lower bound of the two-sided 90% confidence interval (CI) for the mean treatment difference (telcagepant-placebo) in TET was more than -60 s. There were no significant between-treatment differences in TET (mean treatment difference: -6.90 (90% CI: -17.66, 3.86) seconds), maximum exercise heart rate, or time to 1-mm ST-segment depression using pooled data or with stratification for dose.     

An acute double-blind placebo-controlled study of transdermal glyceryl trinitrate with 12 months' follow-up in patients with stable angina pectoris

In an acute double-blind placebo-controlled randomized crossover study, 1 day of treatment with a glyceryl trinitrate transdermal patch releasing 10 mg glyceryl trinitrate daily was compared with placebo in 40 men with stable angina pectoris. Subsequently, the patients participated in an uncontrolled efficacy and tolerability study during which the transdermal patch was applied to the front of the chest for 22-23 hours daily for 12 months. In the acute study, one patch of glyceryl trinitrate or matching placebo was applied at 8.00 a.m. for 24 h; 48 h later the other treatment was applied. Bicycle ergometry was performed 24 and 16 h before the beginning of the treatment, and 8 and 24 h after each dose. Ergometry was repeated after 1, 3, 6 and 12 months' treatment with one patch daily of glyceryl trinitrate during the long-term open follow-up study. In the acute study, a significant reduction of ST-segment depression was observed with treatment compared with placebo. This reduction persisted throughout the 12 months of the open study. During this period also, the mean number of anginal attacks was reduced from 5.3 to 3.6 during week 1 of treatment, and this reduction was maintained throughout the 12 months of the study. No patient needed to be withdrawn because of systemic side-effects or local intolerance to the patch.     

肝素加运动治疗稳定型心绞痛疗效探讨

为探讨肝素在冠心病治疗中的作用，将２０例冠心病患者分两组进行比较分析。Ａ组：肝素加运动，共１０例患者，按标准方法进行２０次踏车运动试验，每次踏车运动前２０分钟静脉注射肝素钠５０００Ｕ；Ｂ组：单独肝素组，共１０例患者，进行皮下注射１０次，每次肝素钠１００００Ｕ，试验期间不做运动试验。全部患者在第１次应用肝素前２４小时和最后１次应用肝素后２４小时均行症状限制性踏车运动试验。在Ａ组，运动总时间从７．１３±０．８９分钟（ｘ±ｓｘ，下同）增加到１１．６７±１．０４分钟（Ｐ＜０．００１），最大血压心率乘积从２４０４．００±３１２．００ｋＰａ／ｍｉｎ增加到３１８２．００±４９５．００ｋＰａ／ｍｉｎ（Ｐ＜０．００１），而Ｂ组上述参数无明显改变。结论：肝素配合运动能够加速侧枝循环的建立，而单独应用肝素则无此作用。运动诱发心肌缺血可始动肝素再生血管的作用。本试验为冠心病的治疗提供了又一新的、有效的、实用的治疗方法     

Combination treatment with ipragliflozin and metformin: a randomized, double-blind, placebo-controlled study in patients with type 2 diabetes mellitus

BackgroundIpragliflozin (ASP1941) is a selective sodium glucose cotransporter 2 inhibitor in clinical development for the treatment of patients with type 2 diabetes mellitus (T2DM).ObjectivesThe primary objective was to evaluate the safety profile and tolerability of ipragliflozin as a glucose-lowering agent in combination with stable metformin therapy in patients with T2DM. A secondary objective was to evaluate the effect of ipragliflozin on the pharmacokinetic (PK) properties of metformin.MethodsThirty-six patients with T2DM stable on metformin therapy (850, 1000, or 1500 mg bid) were randomized in a double-blind manner to receive ipragliflozin (300 mg qd; n = 18) or matching placebo (n = 18) for 14 days. Safety profiles, including monitoring of hypoglycemic events, treatment-emergent adverse events (TEAEs), laboratory measurements, and vital signs were assessed throughout the study. The PK properties of metformin and ipragliflozin were determined in plasma. The geometric mean ratio and its 90% CI for the maximum plasma concentration and AUC_0–10 were calculated for metformin + ipragliflozin (day 14) versus metformin alone (day ?1). Pharmacodynamic properties were assessed by measurement of urinary glucose excretion over 24 hours (UGE_0–24).ResultsAll the TEAEs, except 1, were mild. Fifteen TEAEs were observed in the ipragliflozin group (7 of 18 patients [38.9%]), and 19 TEAEs were observed in the placebo group in (8 of 18 patients [44.4%]). Treatment-related TEAEs were reported by 3 of 18 patients (16.7%) receiving metformin + ipragliflozin and by 5 of 18 patients (27.8%) receiving metformin + placebo. No hypoglycemic events (blood glucose level <54 mg/L [to convert to millimoles per liter, multiply by 0.0555]) were observed. The geometric mean ratios for C_max and AUC_0–10 of metformin + ipragliflozin versus metformin alone were 1.11 (90% CI, 1.03–1.19) and 1.18 (90% CI, 1.08–1.28), respectively. After ipragliflozin treatment, UGE_0–24 on day 14 (74.9 g) was significantly higher than that in the placebo group (3.6 g) and at baseline (3.3 g).ConclusionsCombination treatment for 14 days with ipragliflozin and metformin was well tolerated in patients withT2DM without hypoglycemia. The addition of ipragliflozin (300 mg qd) to metformin therapy did not result in a clinically relevant change in the PK properties of metformin. ClinicalTrials.gov identifier: NCT01302145.     

Biofeedback-wave rehabilitation therapy in combined treatment of patients with stable angina pectoris

160 patients with stable stress angina pectoris (SSAP) received combined treatment. One of the modalities was information-wave impact generated by devices Azor-IR, Chrono-DMW (microwaves), Chrono-EHF. The impact from Azor-IR proved most effective as it reduced the amount of medication without loss of therapeutic activity.     

Spinal cord stimulation for the treatment of refractory angina pectoris: a multicenter randomized single-blind study (the SCS-ITA trial)

Spinal cord stimulation (SCS) is believed to be effective in treating refractory angina. The need for SCS-related chest paresthesia, however, has hitherto made impossible placebo-controlled trials. Subliminal (non paresthesic) SCS, however, might be also effective on anginal pain. In this trial we compared subliminal SCS with paresthesic SCS and with sham SCS. Twenty-five refractory angina patients, who had never received SCS before, underwent SCS device implantation and were randomized to three groups: paresthesic SCS (group PS; n = 10), subliminal SCS (group SS; n = 7) or “sham” SCS (group NS; n = 8). After 1 month group NS patients were randomized to either group PS or SS. After 1 month, changes in angina episodes (p = 0.016), nitroglycerin use (p = 0.015), angina class (p = 0.02), quality of life score (p = 0.05), and items 2 (p = 0.008) and 3 (p = 0.009) of Seattle angina questionnaire differed significantly among groups. Group PS showed significant improvement in outcomes compared to group NS, whereas there were no significant differences between groups SS and NS; furthermore, only nitroglycerin use differed significantly between groups PS and SS. At 3 months, a significant difference between groups PS and SS was observed in angina attacks (p = 0.002), but not in other variables. Thus, in this study, paresthesic, but not subliminal SCS was superior to sham SCS in improving clinical status in refractory angina patients. The lack of significant differences between PS and SS groups in this small study suggests that a possible role for subliminal SCS in individual patients deserves to be assessed in larger trials with appropriate statistical power.     

Repaglinide versus nateglinide monotherapy: a randomized, multicenter study

OBJECTIVE: A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise. RESEARCH DESIGN AND METHODS: Enrolled patients (n = 150) had received treatment with diet and exercise in the previous 3 months with HbA(1c) >7 and < or =12%. Patients were randomized to receive monotherapy with repaglinide (n = 76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n = 74) (60 mg/meal, maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points were changes in HbA(1c) and fasting plasma glucose (FPG) values from baseline, respectively. Postprandial glucose, insulin, and glucagon were assessed after a liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse events or hypoglycemia. RESULTS: Mean baseline HbA(1c) values were similar in both groups (8.9%). Final HbA(1c) values were lower for repaglinide monotherapy than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA(1c) were significantly greater for repaglinide monotherapy than nateglinide monotherapy (-1.57 vs. -1.04%; P = 0.002). Mean changes in FPG also demonstrated significantly greater efficacy for repaglinide than nateglinide (-57 vs. -18 mg/dl; P < 0.001). HbA(1c) values <7% were achieved by 54% of repaglinide-treated patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated with repaglinide (five subjects with one episode each) who had minor hypoglycemic episodes (blood glucose <50 mg/dl) versus 0 patients for nateglinide. Mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group. CONCLUSIONS: In patients previously treated with diet and exercise, repaglinide and nateglinide had similar postprandial glycemic effects, but repaglinide monotherapy was significantly more effective than nateglinide monotherapy in reducing HbA(1c) and FPG values after 16 weeks of therapy.     

Continuation of a randomized,double-blind,multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia

BACKGROUND: The clinical efficacy and tolerability of linezolid were demonstrated in a previously published, randomized, double-blind, registration study comparing linezolid with vancomycin for the empiric treatment of 396 patients with nosocomial pneumonia. OBJECTIVES: The aims of this study were to obtain additional experience with linezolid and vancomycin in patients with nosocomial pneumonia and to satisfy international regulatory requirements. METHODS: Patients with pneumonia acquired after 48 hours in an inpatient facility were randomly assigned to receive either IV linezolid 600 mg or IV vancomycin 1 g every 12 hours for 7 to 21 consecutive days. Patients also received IV aztreonam 1 to 2 g every 8 hours, which could be discontinued if gram-negative pathogens were not identified. The primary efficacy variables were clinical and microbiologic outcomes in evaluable patients at the follow-up visit 15 to 21 days after the end of therapy. Results from the continuation study were analyzed separately and did not include patients from the previously reported study. RESULTS: A total of 623 patients were enrolled: 321 in the linezolid group and 302 in the vancomycin group. Mean (SD) ages were 63.1 (19.1) years and 61.9 (19.3) years, respectively. Mean (SD) Acute Physiology and Chronic Health Evaluation II scores were 14.1 (5.8) and 14.1 (6.2), respectively. There were no significant differences between the linezolid and vancomycin groups at the follow-up visit in clinical cure rates (114/168 [67.9%] and 111/171 [64.9%]) or microbiologic success rates (47/76 [61.8%] and 42/79 [53.2%]) in evaluable patients (excluding those who had indeterminate or missing outcomes). There were also no significant differences in the rates of all drug-related adverse events (14.0% and 14.0%) or those that occurred in > 1% of patients, including diarrhea (3.7% and 3.0%), nausea (0.3% and 1.3%), and rash (0.6% and 1.7%) in the linezolid and vancomycin groups, respectively. CONCLUSION: In the population studied, linezolid appeared to be as well tolerated and as effective as vancomycin, each in combination with aztreonam.