Concomitant use of nitrates,calcium channel blockers,and beta blockers for optimal antianginal therapy

Despite the introduction of new mechanical techniques for revascularization, pharmacologic therapy continues to be the mainstay of antianginal therapy. The conventional antianginal medications, which include nitrates, beta blockers, and calcium channel blockers, act to correct the imbalance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. All three are appropriate for the management of angina caused by a fixed coronary obstruction, but nitrates and calcium channel blockers, which not only reduce demand but also increase supply, are preferred in cases of angina believed to involve a significant increase in vasomotor tone. Because of the different yet complementary mechanisms of action of the three classes of anti-ischemic drags, use of these agents in combination is a rational approach to the treatment of angina unresponsive to monotherapy. Such combinations have been shown to enhance the therapeutic response achieved with single-agent therapy. In addition, the pharmacologic action of one of the components of the combination regimen may serve to offset side effects typically associated with the other.     

Hepatotoxicity of ethanol: protective effect of calcium channel blockers in isolated hepatocytes

Abstract: This study examines the effects of three calcium channel blockers (verapamil, nifedipine and diltiazem) on isolated rat hepatocytes exposed to ethanol. In the first part of our study, hepatocytes were incubated with increasing concentrations of ethanol (100, 300, 500, 1000 mM) for varying times. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) release were measured to evaluate the cytotoxic effects of ethanol. The concentration of 300 mM and time of incubation of 45 min were chosen for cytoprotection experiments in which calcium channel blockers, at two different concentrations, were added to the medium 30 min prior to the addition of ethanol. ALT, AST and LDH release as well as lipid peroxidation and cellular reduced gluthatione (GSH) were measured. Nifedipine and verapamil (25 μM) reduced ALT, AST and LDH activities. The highest dose of diltiazem (50 μM) was more effective than the lowest one (25 μM). Ethanol caused a significant depletion of cellular GSH content as well as a moderate enhancement of lipid peroxidation. While none of the three calcium channel blockers was able to restore the decrease in GSH levels, diltiazem (25 μM) and nifedipine (50 μM) showed the greatest effect, significantly reducing lipid peroxidation.     

不同钙通道阻滞剂联合叶酸治疗老年轻中度H型高血压的临床研究

目的 评价不同钙通道阻滞剂联合叶酸对老年轻中度高同型半胱氨酸（Hey,H型）高血压患者的疗效。方法 采用随机、单盲、平行对照方法,纳入2011年6月至2014月6月在河北省沧州中西医结合医院心血管病科门诊或住院治疗的原发性H型高血压Ⅰ～Ⅱ级患者90例,其中男42例,女48例,年龄（66.9±3.5）岁。将入选患者随机分为苯磺酸氨氯地平组,苯磺酸左氨氯地平组和非洛地平缓释片组,每组30例,均联合叶酸连续口服药物4周。按时监测血压,并予试验开始前、治疗4周时进行血浆Hcy、一氧化氮（NO）、内皮素?1（ET-1）、超氧化物歧化酶（SOD）、丙二醛（MDA）测定。结果 3种钙通道阻滞剂联合叶酸均可降低老年轻中度H型高血压患者的血压和血浆Hcy水平,且苯磺酸氨氯地平组降低收缩压的幅度和血浆Hcy水平大于其他两组,差异具有统计学意义（P＜0.05）。苯磺酸氨氯地平组,治疗后较治疗前血浆NO和SOD水平升高,ET-1和MDA水平降低,差异具有统计学意义（P＜0.05）。结论 钙通道阻滞剂联合叶酸可用于降低老年轻中度H型高血压患者的血压和血浆Hcy水平,且以苯磺酸氨氯地平联合叶酸为优。     

Controversies concerning calcium antagonists

Summary The paper discusses the controversial attitude regarding the safety of calcium channel blockers (CCBs), especially of the dihydropyridine nifedipine, induced through several meta-analyses of studies with CCBs by Dr. Furberg et al.; as a result, a detrimental effect of CCBs, especially during acute myocardial infarction, has been claimed. Several independent re-analyses of the 16 studies, all performed in the 1980s and mainly using the short-acting nifedipine capsule, did not confirm Furberg's results and showed an insignificant mortality difference between patients on CCBs versus those on control. Nevertheless, new safety studies applying long-acting CCBs (half-lives of 1 or more days) combined with efficacy assessments are necessary, both in hypertension as well as coronary artery disease, to finally clear up this important question.     

钙离子拮抗剂和血管紧张素转换酶抑制剂对高血压患者动脉僵硬度影响的荟萃分析

目的系统评价钙离子拮抗剂（calciumchannelblockers,CCBs）和血管紧张素转换酶抑制剂（angiotensin～converting-enz）,meinhibitor,ACEI）对原发性高血压（高血压）患者血管功能作用的差异。方法按循证医学的要求,制定相应的纳入、排除标准及其检索策略。通过PubMed、EMBASE、OvidEBMReviews、中国期刊全文数据库、中文科技期刊全文数据库、万方数据库。检索相关的临床对照研究,计算机检索时间从各数据库建库至2012年1月;同时辅助其他检索,纳入CCBs和ACEI治疗高血压患者的随机对照试验（randomizedcontrolledtrials,RCT）。两名评价者独立评价纳入研究的质量,并用统一的表格提取资料,采用RevMan5．0软件进行统计分析。比较CCBs和ACEI对高血压患者脉搏波传导速度、收缩压、舒张压、脉压等指标的影响。结果共纳入4篇RCT,共计226例患者。文献异质性检验显示数据存在异质性（Q=54．80,P〈0．001）。荟萃分析结果显示,ACEI在改善动脉僵硬度方面优于CCBs,差异有统计学意义（标准差：135．01,95％CI：59．87。210．16;Z=3．52,P=O．0004,P〈0．05）：但在降低收缩压（标准差=-4．73,95％CI：-9．35—0．12,P〈0．04）和舒张压（标准差=-10．42,95％CI：-19．16—1．69．P〈0．02）方面较CCBs弱;在降低脉压（标准差-6．12,95％CI：-2．3～14．55,P〈O．15）方面与CCBs相比．差异无统计学意义。结论ACEI在改善高血压患者动脉僵硬度方面优于CCBs．该作用与其降压作用无关。     

A computerized intervention to decrease the use of calcium channel blockers in hypertension

Objective

To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic.

Design

A randomized trial.

Setting

The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System, Seattle Division.

Patients/Participants

Clinic providers were randomized to a control group (n=35) or intervention group (n=36). We targeted the providers of patients being treated for hypertension with calcium channel blockers, a class of drug not recommended for initial therapy.

Intervention

An automated computer query identified eligible patients and their providers. A guideline reminder was placed in the charts of patients of intervention providers; the charts of patients of control providers received no reminder.

Measurements and main results

During the 5-month study period, 346 patients were seen by the 36 primary care providers (staff physicians, nurse practitioners, residents, and fellows) in the intervention group, and 373 patients were seen by the 35 providers in the control group. Intervention providers changed 39 patients (11.3%) to other medications during the study period, compared with 1 patient (<1.0%) of control providers (p<.0001). For patients whose therapy was unchanged, providers noted angina in 23.1%, indications other than those for hypertension in 9.5%, intolerable adverse effects with first-line therapy in 13.9%, and inadequte control with first-line therapy in 13.9%. Of those patients without provider-indicated contraindications, 23.6% were switched from calcium channel blockers to first-line agents during the intervention period.

Conclusions

The use of a computerized, clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general, and decreased the use of calcium channel blockers for the treatment of hypertension in particular.     

Acute myocardial infarction caused by multivessel coronary spasm due to calcium channel blocker withdrawal

Calcium channel blockers are a commonly used class of medications for the management of hypertension, angina, and superventricular tachyarrhythmias. Abrupt withdrawal of these agents can precipitate coronary vasospasm, which may result in myocardial infarction. We present the case of a 47‐year‐old woman who sustained an acute myocardial infarction mediated by multivessel coronary vasospasm secondary to verapamil withdrawal and the associated interventional management. © 2011 Wiley‐Liss, Inc.     

Efficacy and safety of calcium channel blockers in hypertensive patients with concomitant left ventricular dysfunction.

The use of calcium channel blockers (CCBs) in the treatment of hypertension and concomitant left ventricular dysfunction is reviewed. Some CCBs, particularly second-generation dihydropyridine agents such as felodipine, isradipine, nicardipine, nimodipine, and nitrendipine, have properties that enhance their usefulness in these patients. All CCBs have a similar mechanism of action. Differences in their selective action at various tissue sites determine which are most appropriate for patients with concomitant hypertension and left ventricular dysfunction. Most CCBs do not produce reflex stimulation of the heart or induce intravascular expansion. While all CCBs produce arteriolar dilation, all local beds and regional circulations in target organs are not affected equally. Most CCBs can decrease cardiac mass, and second-generation CCBs tend to have little or no negative inotropic effects at therapeutic dosages. In addition, they increase blood flow and reduce myocardial oxygen requirements. Because of differences in functional and electrophysiologic effects, specific CCBs may not be appropriate for all patients. Since second-generation dihydropyridine CCBs lack clinically relevant negative inotropic effects, and have been shown to improve exercise tolerance and coronary artery perfusion, they are appropriate for hypertensive patients with left ventricular dysfunction, angina, and coronary heart disease. Second-generation CCBs tend to lack cardiodepressant side effects and are less likely to react with digoxin than are first-generation CCBs.     

A multicentre retrospective study to understand anti-platelet treatment patterns and outcomes of acute coronary syndrome patients in India (TRACE)

Background

There is limited available information for treatment of acute coronary syndrome (ACS) with respect to outcomes, therapeutic agents and treatment practices. Our retrospective registry study collected and evaluated varying anti-platelet treatment strategies and outcomes of ACS patients who were admitted to 9 different tertiary care hospitals in India. This study was carried out to provide an insight to anti-platelet treatment patterns and analyze outcomes of ACS patients in India.

Methods

All the relevant data, including anti-platelet treatment strategies, outcomes and patient treatment compliance were collected from 500 ACS (defined as STEMI, NSTEMI and unstable angina [UA]) cases from January 2007 to December 2009. These ACS cases were randomly collected from the hospital records and included in the analysis. The patient follow up data was acquired either from the hospital records or via telephonic contact for a period of one year following the event.

Results

Out of 500 ACS patients, 59.8% had UA/NSTEMI and 40.2% had STEMI. On hospital admission, aspirin, clopidogrel, statins, beta-blockers and angiotensin converting enzyme inhibitors (ACE-Is) were used by 83%, 83%, 68%, 43.2% and 31.6% patients, respectively. On discharge, aspirin, clopidogrel, statins and beta-blockers were used by 90.2%, 88%, 80.6%, and 59% patients, respectively. The average patient compliance to statins, clopidogrel and aspirin was recorded as 74.28%, 69.7% and 68.66%, respectively during discharge and follow-up visits. Greater than 50% of ACS patients after discharge were lost to follow-up and as a result there was significant drop in the number of clinical events reported.

Conclusion

This pilot study conducted in tertiary care centers in India showed that patients with ACS were more often diagnosed with UA/NSTEMI as compared to STEMI and reported maximum compliance to statins, clopidogrel and aspirin after discharge over 1 year follow-up. More ACS patients were lost to follow up that resulted in low reporting of clinical outcomes, following discharge upto 1 year.     

The efficacy and safety of arotinolol combined with a different calcium channel blocker in the treatment of Chinese patients with essential hypertension: a one-year follow-up study

Background: Combined treatment of a calcium antagonist and α/β-adrenoreceptor blocker is expected to offer some advantages in the management of hypertension; however, their antihypertensive efficacy and safety remain relatively under-explored.

Methods: The current study addresses the 24-h antihypertensive efficacy and safety of arotinolol combined with a different calcium channel blocker. One-hundred fifty-two patients were randomly divided into three groups: nifedipine, amlodipine and felodipine group. In each group, the antihypertensive treatment dose was 30?mg/d, 5?mg/d, 5?mg/d long acting nifedipine, amlodipine, felodipine plus 20?mg/d arotinolol, respectively. Blood pressure was measured in ABPM devices and mercury manometer.

Results: The result showed that the effective rate of one year antihypertensive treatment of arotinolol combined with nifedipine was 51 of 53, significantly effective (p?p?>?0.05) in controlled rate of morning peak blood pressure between treatment of arotinolol combined with amlodipine and arotinolol combined with nifedipine, but there was a significant difference (p?Conclusions: The therapy approached of arotinolol combined with nifedipine or amlodipine could be effective and well-tolerated, and they can be used as the better chosen antihypertensive drug.     

Nicardipine, a new calcium channel blocker: role for vascular selectivity

Calcium channel blockers are important drugs for the treatment of chronic stable angina. However, negative inotropic and dromotropic effects may limit their usefulness in patients with atrioventricular conduction abnormalities or left ventricular dysfunction. A new generation of calcium channel blockers will soon be available that have a more vascular selective action than currently available agents. Of the new agents, nicardipine has been most extensively studied. In experimental studies, nicardipine is more specific for vascular smooth muscle than for cardiac smooth muscle and for coronary than peripheral vasculature. In controlled trials, nicardipine exhibited efficacy and safety that was comparable to older calcium blockers or beta blockers. However, nicardipine was associated with minimal negative inotropic or dromotropic effects even in patients with existing left ventricular dysfunction. Thus, nicardipine may have an advantage over existing calcium channel blockers, especially in patients with underlying cardiac disease.     

老年急性心肌梗死介入治疗的临床结果和成本趋势分析

目的　分析老年人急性心肌梗死 (AMI)介入治疗的临床结果和成本趋势。　 方法 　收集从 1996～2 0 0 1年 45 7例老年人AMI患者的临床资料。医疗成本资料从医院的信息管理系统获得。　 结果 　 2 0 0 1年进行冠状动脉介入 (PCI)治疗的老年患者比 1996年增加约 2 7 4% ,1996年与 2 0 0 1年因任何原因再住院患者的比例分别为5 3 3 %和 17 0 % (P <0 0 5 ) ,与PCI治疗有关的再住院患者的比例分别为 40 0 %和 3 7% (P <0 0 5 ) ,再次血管重建术患者的比例分别为 13 3 %和 1 5 % (P <0 0 5 )。 2 0 0 1年PCI的治疗成本比 1996年减少约 8744元 ,其中 99%是手术费的减少。　 结论　近几年老年人AMI介入治疗的临床结果是有改进的。PCI治疗成本的减少主要是手术费的减少 ,可能与再次血管重建术的比例减少有一定的关系     

二氢吡啶类钙通道阻滞剂在慢性稳定性冠心病中应用中国专家共识

<正>引言钙通道阻滞剂(CCB)是临床广泛应用的一类心血管药物。20世纪60年代,Fleckenstein发现CCB有抗心绞痛作用,1975年硝苯地平开始用于治疗心绞痛。1995年Furberg等根据短效硝苯地平小规模临床研究的荟萃分析,对CCB的安全性提出质     

纤维蛋白原浓度变化在急性冠脉综合征中的临床意义

目的:探讨血浆纤维蛋白原(Fg)浓度变化与急性冠状动脉综合征(ACS)的关系。方法:对37例稳定性心绞痛、32例不稳定性心绞痛、31例急性心肌梗死和42例正常对照者分别进行血浆纤维蛋白原浓度测定,并分组进行比较。结果:(1)冠心病各组Fg浓度显著高于正常对照组(P<0.01)。(2)冠心病各组之间随冠脉事件的严重程度,Fg有增高趋势,不稳定性心绞痛和心肌梗死组血浆Fg水平明显高于稳定性心绞痛组(P<0.05)。结论:Fg参与冠心病的发病过程,其升高对冠心病有一定的预测价值,Fg浓度与急性期冠脉事件和ACS严重程度可能相关。     

Differential release of cardiac enzymes after percutaneous coronary intervention.

We hypothesized that using calcium channel blockers (CCBs) that dilate microvasculature during percutaneous coronary intervention (PCI) would result in lower postprocedural creatine phosphokinase (CPK). PCI can be complicated by elevated CPK that has been associated with impaired microvascular perfusion. Nitroglycerin (NTG), the conventional PCI vasodilator, dilates epicardial arteries but does not affect the microvasculature. We hypothesized that using CCBs that dilate the microvasculature would result in lower postprocedural CPK values. Patients (n = 816) without evidence of acute myonecrosis undergoing PCI were divided into two groups based on whether they received intracoronary NTG or CCB during PCI. Postprocedural CPK values were compared using a repeated-measures ANOVA and a random coefficient model. By repeated-measures analysis, the NTG group had CPK values of 88%, 83%, and 89% of the CCB group's CPK values at < 8, 8-14, and > 14 hr after PCI (P = 0.0080, 0.0002, and 0.0244), respectively. In a random coefficient model, the NTG group had CPK values 84%, 84%, and 89% of the CCB group's mean CPK values at 6, 12, and 18 hr after PCI (P = 0.0003, 0.0006, and 0.0403), respectively. Peak CPK values occurred earlier with CCB, although the maximal CPK was similar in both groups. Intracoronary CCB use is associated with an accelerated release of CPK after PCI compared with NTG. This is consistent with more efficient relief of microvascular obstruction with CCB. It suggests that myonecrosis may originate with vascular trauma at the time of PCI and its enzymatic expression is modifiable with different vasodilators.     

B-type natriuretic peptide: a novel early blood marker of acute myocardial infarction in patients with chest pain and no ST-segment elevation.

AIMS: This study was undertaken to determine the diagnostic value of admission B-type natriuretic peptide (BNP) for acute myocardial infarction (AMI) in patients with acute chest pain and no ST-segment elevation. METHODS AND RESULTS: A prospective study with 631 consecutive patients was conducted in the emergency department. Non-ST elevation AMI was present in 72 patients and their median admission BNP level was significantly higher than in unstable angina and non-acute coronary syndrome patients. Sensitivity of admission BNP for AMI (cut-off value of 100 pg/mL) was significantly higher than creatine kinase-MB (CKMB) and troponin-I on admission (70.8 vs. 45.8 vs. 50.7%, respectively, P<0.0001) and specificity was 68.9%. Simultaneous use of these markers significantly improved sensitivity to 87.3% and the negative predictive value to 97.3%. In multiple logistic regression analysis, admission BNP was a significant independent predictor of AMI, even when CKMB and troponin-I were present in the model. CONCLUSION: BNP is a useful adjunct to standard cardiac markers in patients presenting to the emergency department with chest pain and no ST-segment elevation, particularly if initial CKMB and/or troponin-I are non-diagnostic.     

老年人第一次急性心肌梗死前一周内心绞痛对患者预后的影响

目的　探讨老年病人第一次急性心肌梗死前 1周内先兆心绞痛对患者近期预后的影响。方法　记录并分析 14 7例第一次心肌梗死的老年人 (≥ 6 5岁 ,n =74 )和成年人 (<6 5岁 ,n =73)的临床症状、体检、心电图、实验室和超声心电图等临床资料。结果　有先兆心绞痛的老年病人与无心绞痛的相比 ,住院死亡率、心力衰竭 /休克和恶性心律失常发生率较低 (0 %对 10 % ,P <0 0 5 ;13%对 4 0 % ,P <0 0 1;2 1%对 6 0 % ,P <0 0 1)。无先兆心绞痛的老年病人与有心绞痛的相比 ,左心室功能低下者 (LVEF <4 0 % ) ,80 %对 2 5 % ,P <0 0 1。结论　老年病人第一次心肌梗死前 1周内先兆心绞痛对患者住院期间心脏事件有一定影响     

钙拮抗剂抗肝纤维化的实验与临床研究

目的:研究钙通道阻滞刑(CCB)抗肝纤维化的作用。方法:应用CCB汉防己甲素(Tet).维拉帕米(Ver)对实验性肝纤维化大鼠及115例慢性肝病患者抗肝纤维化治疗,并临床随访36个月。结果:血清Ⅲ型前胶原肽(PⅢP)及血清透明质酸(HA)含量与治疗前相比明显降低(P<0.01);14例(15.4％)肝纤维化消失,54例(58.1％)胶原纤维沉积明显减轻,19例(20.4％)胶原纤维轻度减轻,炎性细胞浸润明显减轻或消失,储脂细胞(FSC)数量及内质网、线粒体平均面积均减少,总有效率为93.6％,与对照组相比有非常显著差异(P<0.01-0.001)。结论:CCB对肝纤维化有治疗作用。     

Baseline characteristics,management practices,and long-term outcomes among patients with first presentation acute myocardial infarction in the Second Gulf Registry of Acute Coronary Events (Gulf RACE-II)

Background and objectives

Limited data are available highlighting the different clinical aspects of acute coronary syndrome (ACS) patients, especially in Gulf countries. In this study, we aimed to compare patients who presented with acute myocardial infarction (AMI) as the first presentation of patients who have a history of ACS in terms of initial presentation, medical history, laboratory findings, and overall mortality.