Comparison of bopindolol and atenolol in chronic stable angina pectoris

Summary The efficacy of bopindolol and atenolol in the treatment of patients with chronic stable angina pectoris have been compared in a double blind, randomized study.Both bopindolol 1 mg and atenolol 100 mg for 6 weeks increased mean exercise time (25% and 22%, respectively, compared to placebo), time to angina (27% and 25%), and time to 1 mm of ST-segment depression (32% and 20%).Both drugs reduced ST-segment depression similarly at maximal and submaximal work levels.There was no significant difference in their antianginal efficacy.     

Antianginal effect of conventional and controlled release diltiazem in stable angina pectoris

Two preparations of diltiazem, controlled release (CR) given twice a day (b.i.d.) and plain given 4 times a day (q.i.d.), were compared in a multicentre, double-blind, crossover study in 41 patients with stable angina pectoris. Therapeutic efficacy was assessed with maximal exercise tests, patient recordings on nitroglycerine consumption and angina attacks. No significant differences between the CR and plain tablets were seen in any of the efficacy variables. Maximal workload significantly increased from 127 W on placebo to 146 W on CR tablets and to 147 W on plain tablets. Anginal attacks/week significantly decreased from 11.7 on placebo to 4.9 on CR tablets and to 5.0 on plain tablets. Consumption of nitroglycerine tablets/week significantly decreased from 6.3 on placebo to 2.6 and to 3.4 on CR and plain-tablets, respectively. The number or the seriousness of the adverse events did not differ between the groups. The results imply that diltiazem CR b.i.d. is equally potent and safe as conventional diltiazem q.i.d. in the control of stable angina pectoris.     

Slow release nifedipine plus atenolol in chronic stable angina pectoris.

1. The effects of adding slow release nifedipine in doses of 20 mg and 40 mg twice daily to atenolol therapy (50 mg twice daily) were assessed in 18 patients with chronic stable angina. 2. The addition of the lower dose of nifedipine to atenolol did not significantly alter the weekly consumption of glyceryl trinitrate or the mean number of anginal attacks as assessed by diary cards. However, 2 h after dosing there was a significant prolongation during stress testing in the time to onset of both 1 mm ST depression on the ECG (by 28%) and to angina (by 37%) compared with atenolol alone, but no benefit was apparent by 12 h after dosing. 3. At a dose of 40 mg twice daily, nifedipine significantly reduced glyceryl trinitrate consumption by 25% and the number of anginal attacks by 36%. The times to onset of ST depression and angina were increased by 37% and 55% respectively at 2 h and by 24% and 26% respectively 12 h after dosing. 4. Analysis of the frequency distribution of anginal attacks showed decreasing efficacy with time after administration of nifedipine. The overall results also suggest a relationship between efficacy and the plasma nifedipine concentration, with a mean 20% improvement in time to development of angina occurring at a nifedipine plasma concentration of approximately 30-40 ng ml-1. 5. In conclusion, the reduction of effort-related angina by nifedipine is related to its plasma concentration and the effective duration of action of the 20 mg slow release formulation is less than 12 h.     

Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial

BACKGROUND AND OBJECTIVE: Current medical therapies for the symptoms of angina pectoris aim to improve oxygen supply and reduce oxygen demand in the myocardium. Not all patients respond to current antianginal monotherapy, or even combination therapy, and a new class of antianginal drug that complements existing therapies would be useful. This study was undertaken to compare the antianginal and anti-ischaemic effects of the novel heart-rate-lowering agent ivabradine and of the calcium channel antagonist amlodipine. PATIENTS AND METHODS: Patients with a >/=3-month history of chronic, stable effort-induced angina were randomised to receive ivabradine 7.5mg (n = 400) or 10mg (n = 391) twice daily or amlodipine 10mg once daily (n = 404) for a 3-month, double-blind period. Bicycle exercise tolerance tests were performed at baseline and monthly intervals. The primary efficacy criterion was the change from baseline in total exercise duration after 3 months of treatment. Secondary efficacy criteria included changes in time to angina onset and time to 1mm ST-segment depression, rate-pressure product at trough drug activity, as well as short-acting nitrate use and anginal attack frequency (as recorded in patient diaries). RESULTS: At 3 months, total exercise duration was improved by 27.6 +/- 91.7, 21.7 +/- 94.5 and 31.2 +/- 92.0 seconds with ivabradine 7.5 and 10mg and amlodipine, respectively, both ivabradine groups were comparable to amlodipine (p-value for noninferiority < 0.001). Similar results were observed for time to angina onset and time to 1mm ST-segment depression. Heart rate decreased significantly by 11-13 beats/min at rest and by 12-15 beats/min at peak of exercise with ivabradine but not amlodipine, and rate-pressure product decreased more with ivabradine than amlodipine (p-value vs amlodipine <0.001, at rest and at peak of exercise). Anginal attack frequency and short-acting nitrate use decreased substantially in all treatment groups with no significant difference between treatment groups. The most frequent adverse events were visual symptoms and sinus bradycardia with ivabradine (0.8% and 0.4% withdrawals, respectively) and peripheral oedema with amlodipine (1.5% withdrawals). CONCLUSIONS: In patients with stable angina, ivabradine has comparable efficacy to amlodipine in improving exercise tolerance, a superior effect on the reduction of rate-pressure product (a surrogate marker of myocardial oxygen consumption) and similar safety.     

盐酸曲美他嗪治疗稳定型心绞痛临床疗效观察

目的观察盐酸曲美他嗪（万爽力）治疗稳定型心绞痛的临床效果。方法将50例稳定型劳力型心绞痛患者随机分为两组。观察组25例,予口服万爽力20mg,3次/d、联合倍他乐克（美托洛克）、伯基（肠道阿司匹林）、长效的硝酸脂类、辛伐他汀等治疗;对照组25例,予口服倍他乐克、伯基、长效的硝酸脂类、辛伐他汀等治疗,12周为1个疗程。观察两组用药前后心绞痛发作情况、运动耐受改善情况、心功能及血压、心率、心电图的变化。结果观察组与对照组均能减少心绞痛发作,运动耐受及心电图均得到改善,但两组比较差异有统计学意义（P〈0.05）。结论万爽力联合其他药物对稳定型心绞痛患者疗效显著。     

曲美他嗪治疗稳定性心绞痛的疗效观察

目的评价曲美他嗪(TMZ)治疗稳定性心绞痛的临床疗效.方法120例稳定性心绞痛患者随机分为曲美他嗪组(62例)和对照组(58例),对照组常规服用硝酸酯类、血管紧张素转换酶抑制剂、他汀类调脂药、血小板抑制剂、β受体阻滞剂,曲美他嗪组在服用上述药物的基础上加服TMZ 20mg,每天3次治疗8周.观察两组治疗前后有效率、运动试验结果以及治疗期间的心血管事件发生率.结果与试验前相比,曲美他嗪组较对照组运动时间延长10%和运动总作功提高25%(P＜0.05),运动后ST段下降1mV时间均明显延长30%(P＜0.001).且硝酸甘油消耗量明显减少40%,治疗组较对照组心血管事件发生率明显降低(P＜0.05).结论在常规抗心绞痛药物基础上加用TMZ,可减轻患者心绞痛症状,增加运动耐量,心血管危险降低.     

Twenty-four-hour beta-blockade in stable angina pectoris: a study of atenolol and betaxolol.

We examined the importance of a long plasma half-life (t1/2) on the antianginal effects of beta-blockade by comparing equivalent doses of once-daily atenolol 100 mg (t1/2 6-8 h) and betaxolol 20 mg (t1/2 20-22 h) in a double-blind placebo-controlled cross-over study of 20 patients with stable angina pectoris. At 20 h postdose, heart rate (HR) was lower with betaxolol than with atenolol whereas blood pressure (BP) was equally reduced by both drugs. Twenty-four-hour ambulatory HR recording demonstrated that this difference existed for the last 6 h of the dosage cycle. During treadmill exercise, HR remained lower with betaxolol than with atenolol and exercise time was significantly prolonged only by betaxolol. With placebo, radionuclide ventriculography demonstrated that left ventricular ejection fraction (LVEF) decreased during exercise. Betaxolol, but not atenolol, significantly attenuated the exercise-induced decrease in EF. Thus, the long plasma t1/2 of betaxolol is associated with a reduction in exercise-induced ischemia when tested toward the end of the 24-h dosage cycle. Plasma t1/2 therefore is of clinical relevance to the antianginal, but not antihypertensive, actions of beta-blockers.     

曲美他嗪治疗劳力型心绞痛临床观察

目的：观察曲美他嗪治疗经冠状动脉造影确诊的劳力型心绞痛的临床疗效。方法：观察曲美他嗪治疗（60mg,d）前后50例劳力型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、运动达到ST段压低1mm和出现心绞痛的时间、心率及血压。结果：曲美他嗪洽疗后劳力型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、运动达到ST段压低1mm和出现心绞痛的时间较治疗前明显改善（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的劳力型心绞痛患者的临床表现。     

盐酸曲美他嗪治疗稳定型心绞痛临床疗效分析

目的观察盐酸曲美他嗪治疗稳定型心绞痛的临床效果。方法将82例稳定型劳力型心绞痛患者随机分为两组。治疗组41例,予口服万爽力20mg,3次/d、联合倍他乐克、肠道阿司匹林片、长效的硝酸脂类、辛伐他汀等治疗;对照组41例,予口服倍他乐克、肠道阿司匹林片、长效的硝酸脂类、辛伐他汀等治疗,l2周为1个疗程。观察两组用药前后心绞痛发作情况、运动耐受改善情况、心功能及血压、心率、心电图的变化。结果治疗组与对照组均能减少心绞痛发作,运动耐受及心电图均得到改善,但两组比较差异有统计学意义（P〈0.05）。结论盐酸曲美他嗪联合其他药物对稳定型心绞痛患者疗效显著。     

Anti-anginal and anti-ischemic effects of the selective beta-blocker talinolol in patients with stable angina pectoris

OBJECTIVE: To determine the dose dependency of the anti-anginal and antiischemic effects of the selective beta-blocker talinolol administered once-daily in a randomized, double-blind, placebo-controlled multicenter study in patients with stable angina pectoris. METHODS: Standardized bicycle ergometry at baseline and after 3 and 6 weeks of treatment was used to assess exercise capacity. The primary endpoint was the change in the maximum exercise time (MET) 24 +/- 1 h after the last intake of study medication compared to baseline. Secondary efficacy parameters were time to onset of angina, time to 1 mm ST segment depression, angina attacks, consumption of short-acting nitrates, blood pressure and pulse rate. Patients were randomly allocated to treatment with talinolol (100, 200 or 300 mg once daily) or placebo for a period of 6 weeks. RESULTS: A total of 241 outpatients (204 male and 37 female) aged between 34 and 83 years, were randomized in 31 centers in Germany, Poland and the Czech Republic. At the end of treatment, the primary endpoint (change in MET compared to baseline) showed no significant difference between the talinolol groups and placebo. The means of MET prolongation ranged from 27.4 sec under placebo to a maximum of 47.6 sec in the 200 mg group. However, the time to 1 mm ST segment depression during exercise increased markedly with talinolol, the difference to placebo reaching statistical significance with the 200 mg/d dose (80.1 +/- 32.7 sec, p = 0.0182) and 300 mg/d dose (82.0 +/- 31.6 sec, p = 0.0127). In the case of the other secondary variables, the most pronounced effects were recorded for talinolol doses of 200 and 300 mg/d. Talinolol significantly inhibited the exercise-induced increase in heart rate and blood pressure. The decrease in rate pressure product at 100 W workload was statistically significant with all administered talinolol doses (delta from baseline to final visit 3090, 4351 and 4291 for 100, 200 and 300 mg/d, respectively, p < 0.0001). Despite once-daily dosing, talinolol at doses up to 300 mg/d was very well tolerated. No unexpected adverse drug reactions were observed. CONCLUSION: The results show that talinolol administered once daily in a dosage of 200 - 300 mg/d is effective and safe in the management of chronic stable angina.     

稳定型心绞痛,不稳定心绞痛,急性心肌梗死的冠脉造影特点

目的探讨稳定型心绞痛(SAP),不稳定心绞痛(UAP),急性心肌梗塞(AMI)临床表现与冠脉造影特点.方法分析冠脉病变与冠心病危险因子之间的关系.结果AMI,UAP以单支病变为主,SAP则以双支病变为主且SAP平均冠脉病变数,冠脉狭窄程度,冠脉完全闭塞数均多于UAP及AMI组,吸烟人数在AMI组中多于SAP及UAP组.结论急性冠脉综合症与冠脉粥样硬化狭窄程度无关,冠脉造影不能预测斑块破裂,吸烟是AMI重要的触发因素.     

阿托伐他汀对稳定型心绞痛的临床疗效观察

目的：观察阿托伐他汀对稳定型心绞痛患者C反应蛋白（CRP）的影响。方法：65例稳定型心绞痛患者随机分为对照组和阿托伐他汀治疗组。对照组给予阿斯匹林、β-受体阻滞剂、硝酸酯类等常规治疗,治疗组在常规治疗基础上给予阿托伐他汀20mg／d,疗程2周。分别在治疗前后观察和记录心绞痛发生的次数、心电图的改变,同时检测血脂和血清hs—CRP水平。结果：两组患者的心绞痛发生次数减少,心电图提示心肌缺血明显改善;治疗组血脂和hs—CRP较对照组明显下降（P〈0．05）。结论：阿托伐他汀可明显降低稳定型心绞痛患者hs—CRP水平,     

Suppressed anti-aggregating and cGMP-elevating effects of sodium nitroprusside in platelets from patients with stable angina pectoris

Platelet hyperactivity plays an important role in the pathogenesis of cardio-vascular diseases. In patients with stable angina pectoris, we have recently demonstrated that nitroglycerin suppressed the increased platelet aggregability. The anti-aggregating effect of NTG and other nitrovasodilators is mediated by platelet guanylate cyclase, which generates cyclic GMP (cGMP) in response to nitric oxide (NO) liberated from the nitrovasodilator molecule. In the current study we utilised a more direct NO donor, sodium nitroprusside (SNP), to examine reversal of ADP-induced platelet aggregation in comparison with intraplatelet cGMP elevation in platelets from normal subjects (n = 22) and patients with stable angina pectoris (n = 23).Concentrations of SNP associated with 50% reversal of aggregation were 2.7 ± 0.4 × 10^–7 mol/L with normal subjects and 4.5 ± 0.5 × 10^–6 mol/L with patients (P < 0.01). SNP produced a concentration-dependent elevation of intraplatelet cGMP content: with 10^–4 mol/L SNP this was 17-fold for normals and 5-fold for patients (P < 0.01). An increase in cAMP content was seen only with 10^–4 mol/L SNP, and was 157 ± 11% of baseline in platelets from normal subjects and 138 ± 14% in patients. There was a strong interrelationship between cGMP-stimulating and anti-aggregating effects of SNP. The decrease in cGMP responsiveness to SNP was not related to a dysfunction of platelet guanylate cyclase; neither basal nor SNP-stimulated activity of the enzyme varied significantly between normal subjects and patients. Lipophilic derivatives of cGMP (db-cGMP) and cAMP (db-cAMP) caused reversal of aggregation; there was a nonsignificant trend towards decreased responsiveness of platelets from patients to both db-cGMP and db-cAMP.The observed decrease in responsiveness of platelets from angina patients to anti-aggregating effects of the exogenous NO donor, SNP, can therefore be attributed to suppressed cGMP accumulation. These results imply reduced platelet sensitivity to endogenous NO (endothelium-derived relaxing factor); this might contribute to platelet hyperaggregability observed in angina pectoris.     

冠心病稳定型心绞痛患者降脂治疗临床分析

目的探讨舒降之对稳定性心绞痛患者血脂的影响。方法选择80例诊断明确的稳定性心绞痛患者,随机分成两组,在常规治疗的基础上治疗组给予辛伐他汀(默沙东制药有限公司生产)20mg,每日晚顿服,4周为1疗程,连续用药3个疗程,观察治疗前后血脂浓度的变化。结果使用辛伐他汀治疗后的患者血清总胆固醇、甘油三脂、低密度脂蛋白显著降低、高密度脂蛋白上升。结论应用辛伐他汀治疗稳定型心绞痛能有效降低血脂水平。     

Anti-ischaemic and anti-anginal activity of atenolol, nifedipine and their combination in stable, chronic effort angina

To assess the anti-anginal and anti-ischaemic activity of the beta-blocker atenolol (ATN) and the calcium antagonist nifedipine (NIFE) and their combination in coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Ten male patients (mean age: 58 +/- 2.9 years) suffering from a stable effort angina were studied. The study lasted 14 weeks: after 2 weeks of wash-out, patients were randomly assigned to ATN (100 mg/day) and placebo-NIFE, or placebo-ATN and NIFE (10 mg three times/day), or ATN (100 mg) plus NIFE (10 mg three times/day) for 4 weeks. Maximal symptom-limited stress tests on a bicycle (10 watt/min) during the wash-out period (on days 10 and 14) and at the end of each treatment period were performed. All treatments significantly increased the work load at 1 mm ST depression, the angina threshold and the total work, and reduced ST depression at the maximal common work and at the maximal work. Also the atenolol-nifedipine combination significantly reduced ST depression at maximal common work and maximal work as compared to ATN and NIFE alone. In conclusion, this study confirms the anti-ischaemic and anti-anginal activity of both atenolol and nifedipine in stable effort angina and shows that their combination is able to increase anti-ischaemic activity.     

曲美他嗪与美托洛尔联合治疗稳定型心绞痛

目的 :评价曲美他嗪和美托洛尔联合治疗稳定型心绞痛的疗效。方法 :选择稳定型心绞痛的病人 94例 ,随机分成 2组。治疗组 4 8例给曲美他嗪 2 0mg ,po ,tid和美托洛尔 12 .5mg ,po ,bid ,疗程 4wk。对照组 4 6例给美托洛尔 12 .5mg ,po ,bid及安慰剂 ,po ,tid ,疗程 4wk。结果 :治疗前后 2组心绞痛发作次数 ,硝酸甘油消耗量和静息、运动时血压心率的二项乘积差值分别为 (- 6± 4 )次·wk- 1和 (- 3.3± 2 .2 )次·wk- 1,(- 4± 3)mg·wk- 1和(- 2 .1± 1.4 )mg·wk- 1,- 1198± 4 5 8和 - 82 8±5 36,- 2 0 0 6± 1131和 - 616± 14 65 (P <0 .0 1)。结论 :曲美他嗪联合美托洛尔治疗稳定型心绞痛疗效确切。     

Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina

Epicardial coronary stenosis causes myocardial ischemia; however, the role of coronary microvessels is poorly understood in the pathogenesis of effort angina. We have previously demonstrated that Rho-kinase pathway is substantially involved in coronary arterial hyperconstriction in patients with vasospastic angina and those with microvascular angina. In the present study, we tested our hypothesis that Rho-kinase is involved in coronary microvascular constriction in patients with effort angina. Intracoronary administration of fasudil (300 microg/min for 15 min), a specific Rho-kinase inhibitor, significantly increased oxygen saturation in coronary sinus vein from 37 +/- 3% to 41 +/- 3% (P < 0.05) but not in six age-matched controls (from 42 +/- 3% to 43 +/- 3%, P = NS). Furthermore, the fasudil treatment significantly ameliorated pacing-induced myocardial ischemia in patients with effort angina (magnitudes of symptom: 1.5 +/- 0.6 to 0.6 +/- 0.4, P < 0.01; ischemic ST-segment depression, 1.8 +/- 0.3 to 1.0 +/- 0.2 mm, P < 0.01; percent lactate production, 50 +/- 17% to 0.4 +/- 7%, P < 0.01) without significant hemodynamic changes. These results provide the first evidence that Rho-kinase is substantially involved in coronary microvascular dysfunction associated with myocardial ischemia in patients with effort angina, suggesting that Rho-kinase can be a novel therapeutic target in ischemic heart disease.     

Short-term and chronic effects of transdermal nitroglycerin in stable angina pectoris

Thirty-five patients with stable angina pectoris (AHA functional class II or III) entered a 5-week short-term study to determine the efficacy and safety of a transdermal therapeutic system of nitroglycerin (TDN; 5 to 20 mg/day). Nineteen of these patients were available for a final reassessment in a long-term follow-up after at least 1 year of continuous therapy; hence, total treatment time exceeded 8,400 patient-days. The therapeutic efficacy of TDN was determined from weekly patient diaries of angina frequency, as well as the clinical assessment of functional class according to the criteria of the American Heart Association. Frequency of angina was reduced from ten to less than three attacks per week in all treatment groups, irrespective of angina severity at the outset, and reduction in anginal frequency was statistically significant (P <0.05) in the 10-, 15-, and 20-mg dosage groups. Sixteen of the 19 patients (84%) who entered the long-term follow-up required no change in dosage, and all 19 patients showed improvement in AHA function class at the final reassessment. Our study showed that TDN exerted a sustained, clinically significant therapeutic benefit during both a short-term study and long-term follow-up in patients with stable angina pectoris.     

Development of tolerance to nifedipine in patients with stable angina pectoris.

1. The possibility of development of tolerance to the anti-ischaemic and anti-anginal effects of nifedipine during sustained administration for 2 months was studied in 15 patients with stable angina pectoris by means of repeated exercise tests on a treadmill. 2. After acute administration of nifedipine (20-30 mg) substantial anti-ischaemic and anti-anginal effects lasted for at least 4 h in all patients. 3. During sustained nifedipine treatment with a dose schedule which provided continuous anti-ischaemic effect during a day (mean daily dose 82.7 +/- 6.0 mg, range 60-120 mg) a substantial attenuation of this effect was registered. The duration of the anti-ischaemic effect was 5.4 +/- 0.3 h after acute administration, decreasing significantly to 3.6 +/- 0.4 h during sustained administration. 4. The attenuation of the nifedipine effect was not associated with worsening of the patients' condition. 5. Plasma concentrations of nifedipine and its metabolite were similar after acute administration and during sustained treatment. Protein binding of nifedipine also remained constant during the study. 6. There was marked interindividual variation in the degree of attenuation of the nifedipine effect during sustained administration. In five patients nearly complete loss of nifedipine efficacy was registered. Eight to ten days after stopping regular administration of nifedipine only partial restoration of nifedipine effect was observed. 7. We conclude that during sustained nifedipine administration tolerance to its anti-ischaemic, anti-anginal and circulatory effects develops in a substantial number of patients with stable angina pectoris.