Open comparative study to assess the efficacy and safety of two calcium antagonists: amlodipine and diltiazem in the treatment of symptomatic myocardial ischemia

The efficacy and safety of amlodipine (5-10 mg once daily) and diltiazem (30-60 mg three times daily) were compared in 40 patients with symptomatic myocardial ischemia. A 2-week placebo run-in period was followed by 10 weeks of open treatment with amlodipine (n = 20) or diltiazem (n = 20). Concomitant treatment with other antianginal drugs (except other calcium antagonists) was permitted throughout the study. The baseline blood pressures were 166/93 and 160/91 mm Hg for the amlodipine group and diltiazem groups, respectively. Amlodipine (mean final daily dose of 9.25 mg) reduced blood pressure by - 27/-11 mm Hg compared with a reduction of - 17/-8 mm Hg for diltiazem (mean final daily dose of 180 mg), with no significant effects on heart rate. A significantly greater reduction in the mean rate-pressure product was observed after amlodipine (-20.8%) when compared with diltiazem (-13.1%) (p < 0.05). Amlodipine reduced the mean weekly angina attacks to zero after 6 weeks of treatment (baseline of 3.4 attacks/week) compared with a reduction from 3.3 to 0.35 attacks/week after 10 weeks of treatment with diltiazem. The amlodipine group had a reduction in mean nitroglycerin consumption from baseline of 1.1 mg/week to zero by week 6, whereas the diltiazem group had reduced mean weekly intake from 0.9 to 0.1 mg at the end of the study. The overall assessment of clinical efficacy was excellent for 100% of amlodipine patients compared with 40% of diltiazem patients. The high-density lipoprotein cholesterol/total cholesterol ratio increased by 15.8% with amlodipine compared to diltiazem, which produced a 4.5% decrease. Amlodipine decreased triglycerides by 7.1% compared to 4.5% with diltiazem. The incidence and severity of side effects was comparable for both treatments. Amlodipine once daily was effective and well tolerated in the treatment of patients with symptomatic myocardial ischemia and was comparable with diltiazem three times daily.     

Drug safety evaluation of amlodipine

INTRODUCTION: Despite the availability of a wide range of antihypertensive medications, in European countries the number of patients not reaching blood pressure control target varies from 59.7% in England to 81.3% in Spain demonstrating substantial unmet need in the effective treatment of arterial hypertension. AREAS COVERED: The authors conducted a review analyzing clinical efficacy and safety of amlodipine, both alone and in combination with other antihypertensive drugs, including the most important studies about amlodipine in the last 15 years. Readers will have a clearer idea of the use of amlodipine, its indications and contraindications, and they will know if amlodipine is a better or worse choice compared to the other antihypertensive drugs. EXPERT OPINION: Amlodipine is not inferior to the other antihypertensive drugs in reducing hypertension and has additional biological effects that are not mediated through blood pressure reduction, including antioxidant activity, inhibition of smooth muscle cell proliferation and enhancement in endothelial NO production. Amlodipine, besides being effective on left ventricular hypertrophy, appears beneficial in slowing down the progression of carotid hypertrophy and atherosclerosis, and can be used in patients with angina pectoris, even if the first choice for angina treatment is β-blockers.     

Drug safety evaluation of amlodipine

Introduction: Despite the availability of a wide range of antihypertensive medications, in European countries the number of patients not reaching blood pressure control target varies from 59.7% in England to 81.3% in Spain demonstrating substantial unmet need in the effective treatment of arterial hypertension.

Areas covered: The authors conducted a review analyzing clinical efficacy and safety of amlodipine, both alone and in combination with other antihypertensive drugs, including the most important studies about amlodipine in the last 15 years. Readers will have a clearer idea of the use of amlodipine, its indications and contraindications, and they will know if amlodipine is a better or worse choice compared to the other antihypertensive drugs.

Expert opinion: Amlodipine is not inferior to the other antihypertensive drugs in reducing hypertension and has additional biological effects that are not mediated through blood pressure reduction, including antioxidant activity, inhibition of smooth muscle cell proliferation and enhancement in endothelial NO production. Amlodipine, besides being effective on left ventricular hypertrophy, appears beneficial in slowing down the progression of carotid hypertrophy and atherosclerosis, and can be used in patients with angina pectoris, even if the first choice for angina treatment is β-blockers.     

氨氯地平治疗轻、中度高血压有效性与安全性的Meta分析

目的 :了解氨氯地平治疗轻、中度高血压有效性及不良反应 (安全性 )的差异。方法 :应用Meta分析对 2 6篇文献 2 8项研究氨氯地平与其他抗高血压药物治疗轻、中度高血压的有效性、安全性进行同质性检验及合并效应量的估计。结果 :(1)同质性检验 :有效性 ,χ2 =2 9.13,自由度为 2 7;安全性 ,χ2 =2 7.95 ,自由度为 2 4 ,两者P均大于 0 .0 5。 (2 )合并效应量的估计 :有效性 ,OR合并 =1.2 6 1,OR合并95 %可信区间为 1.0 18～ 1.5 6 2。OR合并 的检验 :χ2 =4 .5 1,P <0 .0 5 ;安全性 :OR合并 =1.0 13,OR合并95 %可信区间为 0 .80 1～ 1.2 82。OR合并 的检验 :χ2 =0 .0 13,P >0 .0 5。结论 :氨氯地平治疗轻、中度高血压的疗效总体上优于目前常用药物 ,且其安全性较高。     

An evaluation of liraglutide including its efficacy and safety for the treatment of obesity

ABSTRACT

Introduction: The prevalence of obesity is increasing worldwide and associated conditions, particularly type 2 diabetes mellitus (T2DM), also show increasing prevalence. Lifestyle intervention should be the first line of management for obesity but additional pharmacotherapy is often required and bariatric surgery is appropriate in more severe cases. Drugs acting as glucagon-like peptide-1 receptor agonists (GLP-1RAs) developed for the management of T2DM reduce body weight and liraglutide is the first GLP-1RA to be approved for the treatment of obesity in patients with and without T2DM.

Areas covered: In this review of relevant published material, the authors summarize the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of liraglutide for the treatment of obesity.

Expert opinion: Liraglutide effectively reduces body weight and body fat through mechanisms involving reduced appetite and lowered energy intake, independent of its glucose-lowering effects. Like most of the other medications currently available for obesity, liraglutide has some common adverse effects, although generally not serious ones. Liraglutide has additional benefits in reducing cardiovascular events in patients with T2DM but the cost and the need for daily injections may limit its use in obesity. Newer GLP-1RAs, such as semaglutide, or other drugs in development for obesity may have advantages over liraglutide.     

An evaluation of the efficacy and safety of erdafitinib for the treatment of bladder cancer

ABSTRACT

Introduction

Treatment of unresectable or metastatic urothelial carcinoma (UC) has historically relied upon platinum-based chemotherapy and, more recently, immune checkpoint inhibitors. When tumors progress despite those therapies, remaining effective options are limited.     

An open, parallel, comparative evaluation of amlodipine and nitrendipine in the monotherapeutic treatment of mild and moderate essential hypertension

The efficacy and safety of the dihydropyridine calcium antagonists amlodipine and nitrendipine as single-agent therapy of mild to moderate hypertension were compared in an open, parallel-group study. Interim analysis of data from 74 patients (43 male, 31 female) from an expected final total of 96 patients is reported. Amlodipine normalized blood pressure (< or = 90 mm Hg) in 94.7% of patients with a mean final dose of 8.3 mg/day, compared with normalization of blood pressure in 83.3% of patients treated with nitrendipine with a mean final dose of 28.3 mg/day. Only nitrendipine produced a statistically significant increase in heart rate after 2 and 4 weeks of therapy. Nitrendipine-treated patients reported more adverse events (47.2%) than the amlodipine-treated group (26.3%). Two patients from the nitrendipine group discontinued treatment due to treatment-related adverse events and one patient required a dose reduction. In the amlodipine-treated group, all adverse events were mild to moderate and dose reduction was required in one patient. In conclusion, although amlodipine and nitrendipine have comparable antihypertensive efficacy, in this study amlodipine was associated with fewer adverse effects.     

An update on the safety of amlodipine

A previous article on the safety of amlodipine reviewed data from over 4,000 subjects who participated in clinical trials sponsored by Pfizer Central Research. Once-daily amlodipine was shown to be a well-tolerated treatment of hypertension and myocardial ischemia. Although amlodipine is a potent vasodilator, there was a low incidence of side effects such as headache, flushing, and dizziness. Amlodipine was not associated with adverse effects on hematologic or biochemical safety parameters nor on serum cholesterol or triglyceride levels. Amlodipine did not alter electrical conduction in the heart. Amlodipine had a favorable safety profile in comparative trials vs. beta-blockers. The data base of comparative trials vs. other calcium antagonists was small but the toleration of amlodipine was similar to that of verapamil and diltiazem. No data from comparative trials vs. another calcium antagonist of the dihydropyridine class have been available. This article reviews data from recently completed trials vs. nitrendipine and from trials in which amlodipine was used in combination with other agents. Amlodipine was better tolerated than nitrendipine and had a much lower incidence of side effects usually related to vasodilatation. This difference in side-effect profile was especially marked during the first days of treatment. Amlodipine was well tolerated when used in combination with beta-blockers, diuretics, ACE inhibitors, and nitrates. The gradual onset of action and relatively long half-life of amlodipine are the probable cause for the improved toleration in comparison with other dihydropyridines. Besides the low incidence of trivial side effects, increasing clinical experience with amlodipine provides no evidence that amlodipine is a cause of rare but serious adverse effects. It is concluded that amlodipine is an antihypertensive and anti-ischemic agent that has the combined advantages of a good safety profile with once-daily dosage and a smooth onset and long duration of action.     

The efficacy and safety of amlodipine in the treatment of mild and moderate essential hypertension in general practice

The antihypertensive efficacy and safety of amlodipine was evaluated in an open, multicenter general practice study. Hypertensive patients with sitting diastolic blood pressure in the range 95-115 mm Hg entered an initial 2-week baseline period during which they received placebo in a single-blind fashion. The dose of any concomitant antihypertensive treatment was kept constant for 4 weeks prior to baseline evaluations and throughout the study. Patients with an average sitting diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg at two consecutive visits during the baseline period continued to the 8-week dose adjustment phase of the study. Patients were started on 5 mg of amlodipine once daily adjusted after 4 weeks to 10 mg once daily to achieve a target sitting diastolic blood pressure < or = 90 mm Hg. Amlodipine treatment produced significant falls in blood pressure (-23.7/-17.3 mm Hg; p < 0.05) with no effect on heart rate. Amlodipine was well tolerated, with most adverse events being mild or moderate. Investigators' global evaluation of toleration was excellent or good in 92% of patients. Subgroup analysis showed amlodipine to be equally efficacious and well tolerated in elderly or young patients, and in patients taking amlodipine as monotherapy or combination therapy.     

国产氨氯地平治疗慢性肾功能不全并高血压的临床观察

目的 评价国产氨氯地平(兰迪)治疗慢性肾功能不全合并轻中度高血压的降压疗效和安全性.方法 慢性肾功能不全(血清肌酐值265-442 μmol/L)合并高血压患者61例,随机分为两组:兰迪组(31例)、氨氯地平组(络活喜组,30例),分别服用兰迪或络活喜5 mg每日1次,治疗4周末坐位DBP＜80 mm Hg且SBP＜130 mm Hg者继续原剂量治疗至8周末;坐位DBP≥80 mm Hg或SBP≥130 mm Hg者剂量分别加倍至10 mg 每日1次治疗至8周末.分别观察患者服药前后血压、心率和肝肾功能等生化指标变化及其不良反应.结果 61例患者均完成8周的临床试验.降压总有效率兰迪组达87%,络活喜组达90%,若以血压为130/80 mm Hg为靶目标值则:兰迪组8周后11例(36%)达标;络活喜组9例(30%)达标.两组不良反应轻,试验结束时主要实验室检查指标与试验前比较差异无统计学意义.结论 国产氨氯地平(兰迪)5～10 mg,每日1次是治疗慢性肾功能不全合并轻中度肾性高血压有效药物之一,且安全性好.     

An evaluation of the efficacy and safety of Tofogliflozin for the treatment of type II diabetes

Introduction: Accumulating data from recent studies has altered the gold standard of care for diabetes treatment. In patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or those at high risk for CVD, subsequently to lifestyle changes and metformin therapy, the administration of an SGLT-2 inhibitor with established benefits for cardiovascular outcome (CVOT) should be considered.

Areas covered: Tofogliflozin is the most selective SGLT-2 inhibitor and has been approved for the treatment of T2D in Japan. This review summarizes the available data on Tofogliflozin as compared to other SGLT-2 inhibitors, and primarily the three SGLT-2 inhibitors with published CVOT: Empagliflozin, Canagliflozin and Dapagliflozin.

Expert opinion: Tofogliflozin’s higher selectivity profile increases the positive effects on cardiovascular (CV) outcomes and death and reduces side effects. However, the clinical data on Tofogliflozin from both clinical and real-world studies remain sparse and much less abundant than the other main 3 SGLT-2 inhibitors, thus calling for caution and underscoring the need for further research.     

左乙拉西坦单药治疗癫痫的临床疗效和安全性评价

目的探讨左乙拉西坦单药治疗癫痫的临床疗效和安全性。方法选择2014年12月至2016年12月本院收治的癫痫患者作为研究资料,共64例均接受左乙拉西坦单药治疗,回顾性分析治疗6个月后的临床疗效及不良反应发生情况。结果 s CTCS发作类型治疗后发作频率明显低于SPS、CPS、CTCS三种类型,t=2.11,t=3.92,t=3.29,P<0.05;而s CTCS发作类型应答率则显著高于SPS、CPS、CTCS三种类型,χ~2=3.88,χ~2=4.10,χ~2=7.12,P<0.05;不良事件发生率为10.9%。结论对癫痫患者采用左乙拉西坦单药治疗具有良好的治疗效果,且具有较好的耐受性,安全性较高,值得推广应用。     

后腹腔镜与开放手术治疗嗜铬细胞瘤安全性及有效性的Meta分析

目的 评价后腹腔镜手术与开放手术治疗嗜铬细胞瘤的安全性及有效性.方法 检索国内外后腹腔镜与开放手术治疗肾上嗜铬细胞瘤的回顾性研究,截止时间为2016年2月,由2名研究者独立对文献质量评价后采用Review Manager 5.1.0软件进行Meta分析.结果 共纳入13篇符合要求的文献计616例病人.Meta分析结果显示:(1)有效性方面:与开放组相比,腹腔镜组的手术时间及术后住院时间短,肿瘤直径较小.(2)安全性方面:与开放组相比,腹腔镜组的术中出血量少,术后胃肠功能恢复时间、术后下床活动时间及引流时间短,术中输血例数、术中血压升高例数及引流量少,并发症发生率低.结论 后腹腔镜和开放手术均能有效治疗嗜铬细胞瘤,与开放手术相比,后腹腔镜具有手术时间短、标准化、安全性高、并发症发生率相对较低等优点.但后腹腔镜治疗嗜铬细胞瘤的效果及安全性尚需多中心、高质量大样本的随机对照试验进一步验证.     

Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety

ABSTRACT

Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM–5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed—some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds.     

美沙拉嗪治疗炎症性肠病的疗效及安全性

目的观察一种新型美沙拉嗪控释剂(艾迪莎)治疗炎症性肠病(IBD)的疗效和安全性,并同水杨酸偶氮磺胺吡啶(SASP)进行比较。方法本研究是一个随机、多中心、以SASP作对照的临床试验。89例内镜确诊为轻、中度溃疡性结肠炎或克罗恩病急性期(首次发作或复发)的患者随机分成艾迪莎组(n=52)和SASP组(n=37),分别给予艾迪莎或SASP治疗,剂量均为1.0g,qid,疗程6周。服药6周后复查内镜。治疗4和6周对药物疗效进行评价,并观察不良反应。结果在服药4和6周末艾迪莎组患者主观评价为明显好转者分别为52.0%和71.2%,SASP组分别为20.6%和50.0%,2组比较有统计学意义(P<0.05)。艾迪莎组服药6周症状消失率为57.7%,显著高于SASP组(50.0%,P<0.05)。艾迪莎组6周内镜下显示治愈率为26.9%,显著高于SASP组(2.9%,P<0.05)。艾迪莎组总体评价为很好者占42.3%,显著高于SASP组(2.9%,P<0.05)。艾迪莎组和SASP组不良反应的发生率分别为1.9%(1/52)和10.8％(4/37),2组比较无明显差异(P>0.05)。结论艾迪莎是一个治疗IBD的安全有效的药物。     

美托洛尔与硝苯地平治疗老年人无症状性心肌缺血的疗效对比

目的 探讨美托洛尔与硝苯地平治疗老年人无症状性心肌缺血的临床应用价值.方法 选择56例无症状性心肌缺血老年患者,随机数字表法分为美托洛尔组和硝苯地平组各28例.分析两组治疗期间并发症发生情况、治疗前后发作次数及发作时间.结果 美托洛尔组与硝苯地平组患者治疗前发作次数分别为(19.6±3.2)次/周与(18.9±2.8)次/周,发作时间(5131±352)s与(5130±348)s,差异均无统计学意义(均P＞0.05);治疗后发作次数分别为(4.6±2.1)次/周与(7.4±2.1)次/周,发作时间(900±140)s与(1440±240)s,差异均有统计学意义(均P＜0.05).所有患者治疗期间均能耐受,无心肌梗死病例出现.结论 美托洛尔与硝苯地平对于老年人无症状性心肌缺血的治疗较为安全,美托洛尔较硝苯地平治疗效果好.     

美沙拉嗪治疗炎症性肠病的疗效及安全性：—全国多中心临床研究

目的：观察一种新型美沙拉嗪控释剂（艾迪莎）治疗炎症性肠病（IBD）的疗效和安全性。并同水杨酸偶碘胺吡啶（SASP）进行比较。方法：本研究是一个随机、多中心、以SASP作为照的临床试验。89例内镜确诊为轻、中度溃疡性结肠炎或克罗恩病急性期（首次发作或复发）的患者随机分成艾迪莎组（n=52)和SASP组（n=37),分别给予艾迪莎或SASP治疗,剂量均为1．0g,qid疗程6周。服药6周后复查内镜。治疗4和6周对药物疗效进行评价,并观察不良反应。结果：在服药4和6周末艾迪莎组患者主观评价为明显好转者分别为52．0％和71．2％,SASP组分别为20．6％和50．0％,2组比较有统计学意义（P＜0．05）。艾迪莎组服药6周症状消失率为57．75,显著高于SASP组（50．0％,P＜0．05）,艾迪莎组6周内镜下显示治愈率为26．9％,显著高于SASP组（2．9％,P＜0．05）。艾迪莎组总体评价为很好者占42．3％,显著高于SASP组（2．9％,P＜0．05）。艾迪莎组和SASP组不良反应的发生率分别为1．9％（1／52）和10．8％（4／37）,2组比较无明显差异（P＞0．05）。结论：艾迪莎是一个治疗IBD的安全有效的药物。     

那格列奈片治疗2型糖尿病安全性和有效性的临床观察

目的评价那格列奈片治疗2型糖尿病的有效性和安全性。方法 2型糖尿病患者未使用促胰岛素分泌剂以及胰岛素的患者,已经使用二甲双胍和葡萄糖苷酶抑制剂者剂量不变。采用5个中心、随机、双盲、瑞格列奈片对照研究,计划入选240例患者(1:1随机,每组120例),完成研究的2型糖尿病患者231例,那格列奈组115例,对照药物瑞格列奈116例。观察时间12周,治疗前后观察指标包括标准餐(0、60、120分)取血测定血糖和血清胰岛素水平、HbAlc和安全性指标(肝肾功能、血尿常规)。结果与瑞格列奈片相比,那格列奈片治疗2型糖尿病患者 HbAlc下降水平相似,治疗前后HbAlc的变化那格列奈片为(-0．95±1．32)％,瑞格列奈片为(-1．22±1．23)％, 两组之间没有统计学差异,但是每组治疗前后相比均具有统计学差异。标准餐后1h和2h血糖两组较治疗前相比均有统计学意义的下降,餐后2h血糖那格列奈组治疗前后分别为12．72±3．84mmol／L和10．93±3．59mmol／L(P <0．05),瑞格列奈组治疗前后分别为13．28±2．80mmol／L和11．09±3．24mmol／L(P<0．05),但两组之间比较没有统计学差异。使用那格列奈治疗12周后标准餐1h血清胰岛素水平显著升高,治疗前后的水平分别为21．89± 14．01μIU／mL和22．41±13．93μIU／mL(P<0．05),瑞格列奈组治疗前后分别为22．77±17．14μIU／mL和23.06± 17．29μIU／mL(P<0．05),两组之间比较和0分及2h治疗前后均没有差别。两组安全性方面没有差别。结论那格列奈和瑞格列奈一样是安全有效的降血糖药物。     

雷贝拉唑联合奥美拉唑治疗消化性溃疡疗效和安全性评价

目的探讨分析了雷贝拉唑联合奥美拉唑在消化性溃疡治疗过程中的临床疗效以及不良反应。方法 2009年到2011年共收治消化性溃疡患者130例,130例患者随机分为两组,治疗组和对照组,每组患者65例,对照组患者采用口服奥美拉唑进行单独治疗,治疗组患者在对照组治疗的基础上给予雷贝拉唑联合治疗。两组患者在治疗期间均对患者的临床症状以及药物毒副作用进行记录,并分析两组患者治疗的临床有效率。结果治疗组疗效显著性高于对照组,差异具有统计学意义(P<0.05);对照组有4例患者出现头晕以及恶心症状,5例出现腹胀,治疗组3例出现恶心和呕吐以及头晕,4例出现了腹胀,均不影响治疗,均好转,对照组和治疗组患者的不良反应比较差异无统计学意义(P>0.05)。结论雷贝拉唑联合奥美拉唑在治疗消化道溃疡方面具有明显协同效应,其可显著性抑制患者胃酸分泌,清除患者幽门螺杆菌,是临床治疗消化道溃疡较好的药物配伍方案,值得临床推广使用。