Comparison of atenolol and nifedipine in chronic stable angina pectoris

The antiangina effects of atenolol, 50 to 200 mg once daily, or nifedipine, 10 to 30 mg 3 times daily, were evaluated in a multicenter, randomized, double-blind, parallel study of 39 patients with known symptomatic coronary artery disease. Treatment was titrated to produce at least a 30% increase in treadmill exercise duration over placebo baseline and then maintained at that dosage for an additional 3 weeks. Both treatments produced significant (p less than 0.001) increases in duration of exercise, total work and exercise capacity when compared with placebo baseline. These improvements in exercise performance were obtained with significant (p less than 0.001) reductions in both ST-segment depression and rate-pressure product for atenolol compared with nifedipine. Furthermore, the total angina attack rate and rate at rest were significantly (p less than 0.01) less frequent with atenolol than with nifedipine. Hence, the antiischemic effects of atenolol exceeded those of nifedipine, based on ST-segment depression and rate-pressure product at comparable workloads.     

Comparison of carvedilol and atenolol for angina pectoris

The antianginal efficacy of carvedilol, a novel beta-blocking agent with vasodilating action, and atenolol were compared in 12 patients with stable effort angina and a positive stress test response. All patients received single doses of placebo, carvedilol, 25 and 50 mg, and atenolol, 50 mg. Heart rate at rest was reduced by 11 and 12 beats/min with both drugs, but only carvedilol, 50 mg, reduced blood pressure at rest. Both carvedilol, 50 mg, and atenolol, 50 mg, increased mean exercise time (24% and 34%, respectively, compared with placebo), time to angina (35% and 51%, respectively), and time to 1 mm of ST-segment depression (54% and 102%, respectively, p less than 0.05 carvedilol vs atenolol). Carvedilol, 25 mg, produced smaller, directionally similar changes in exercise performance, which did not reach statistical significance except for time to 1 mm of ST depression. Both drugs in the 50-mg dose reduced ST-segment depression similarly at maximal and submaximal work levels and lowered heart rate and rate-pressure product at maximal and submaximal work. Carvedilol, 50 mg alone, significantly lowered maximal systolic pressure and rate-pressure product at 1 mm of ST-segment depression. Despite some evidence of vasodilator activity for carvedilol, there was no significant difference in antianginal efficacy with a conventional beta-blocking drug.     

尼可地尔治疗稳定型心绞痛有效性和安全性的临床研究

目的：探讨尼可地尔治疗冠心病稳定型心绞痛（SAP）的疗效和安全性。方法：收集我院2010年4月至2012年4月门诊及住院的60例SAP患者,随机分为尼可地尔组（28例,口服：尼可地尔5mg,3次/d）,单硝酸异山梨酯组（32例,口服：单硝酸异山梨酯缓释片30mg/d）,两组均同时服用美托洛尔25mg,2次/d、阿托伐他汀20mg,1次/d、阿司匹林100mg,1次/d。4周治疗后分别观察两组心绞痛、心电图、运动耐量和不良事件情况。结果：与单硝酸异山梨酯组比较,尼可地尔组治疗心绞痛有效率（71.9%比96.4%）、改善运动耐量率（68.8%比92.9%）均显著提高（P均〈0.05）;尼可地尔组轻微头痛（25%比10.7%）显著减少（P〈0.05）。结论：尼可地尔能在不增加患者不良事件的基础上,明显提高对稳定型心绞痛患者的疗效。     

A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris

Summary The antianginal activities of nicorandil, 10 and 20 mg bid, and metoprolol, 100 mg bid, were compared in patients with stable effort angina pectoris in a randomized, double-blind parallel group study lasting 7 weeks. Twenty patients were enrolled into the trial and 16 patients completed the study. To evaluate the antiischemic effects of the two drugs, a treadmill exercise test was performed after a 1-week placebo run-in period and 6 weeks of treatment. On the same occasions, weekly sublingual nitroglycerine consumption and the number of anginal attacks were also recorded in the patient's diary. The total duration of exercise increased significantly with both nicorandil, 10 and 20 mg, and metoprolol (p<0.01). Similar improvements were observed in the time to onset of ischemia with both treatments (p<0.01). The double product at maximal comparable workload (MAX 1) was reduced with the two drugs (p<0.05 for nicorandil and p<0.01 for metoprolol), while at the maximal exercise time (MAX 2) it was reduced with metoprolol (p<0.01) and slightly but not significantly increased with both doses of nicorandil. Weekly sublingual nitroglycerine consumption and anginal attacks were also significantly reduced a similar manner by both treatments (p<0.01). In conclusion, nicorandil, 10 and 20 mg bid, exerted an antiischemic effect comparable with that of metoprolol in patients with stable effort angina pectoris.     

Comparison of bevantolol and atenolol in chronic stable angina

A randomized, double-blind, parallel-group study design was used to compare the antianginal efficacy of bevantolol (200 to 400 mg) and atenolol (50 to 100 mg) each administrated once daily for 8 weeks in 39 patients with chronic stable angina. Assessments were made using 24-hour ambulatory monitoring and treadmill exercise testing performed 22 to 24 hours after the last dose of medication. Both groups were comparable at the end of the placebo phase. In the bevantolol group, exercise time increased from 7.9 +/- 0.7 minutes with placebo to 9.3 +/- 0.7 minutes with bevantolol (mean +/- standard error of the mean) (p less than 0.05). Time to 1 mm ST depression was unaltered. Rest and exercise heart rate decreased (p less than 0.0001 and less than 0.0005, respectively) as did exercise double product (p less than 0.0001). In the atenolol group exercise time increased from 7.1 +/- 0.7 minutes with placebo to 8.2 +/- 0.8 minutes with atenolol (p less than 0.02). Time to 1 mm ST depression increased (p less than 0.005) and rest and exercise heart rate and double product decreased (p less than 0.0001 and less than 0.05, respectively). When within-group differences between placebo and active drug were compared for bevantolol and atenolol, no significant differences were detected. Both drugs were well tolerated and reduced ambulatory heart rate throughout the 24 hours. This study confirms that both bevantolol and atenolol are effective antianginal agents. Bevantolol compares well with atenolol in the treatment of patients with chronic angina, and there was a similar response to exercise testing with the 2 drugs.     

Atenolol versus the fixed combination of atenolol and nifedipine in stable angina pectoris

One hundred and fourteen patients (94 male) with chronic stableangina who had a positive exercise test after 4 weeks on atenololalone were randomized to receive either atenolol alone or thefixed combination of atenolol and nifedipine slow release formulationfor 4 weeks in a double-blind cross-over manner. Exercise stresstesting (Bruce protocol) at the end of each treatment perioddemonstrated that the time to the onset of pain and occurrenceof 1 mm ST segment depression improved significantly (P <0.05 and P < 0.001 respectively) whilst on the fixed combinationcompared to atenolol alone. In order to achieve sufficient sensitivityin the analysis of the exercise times, novel statistical methodsbased on survival analysis were used. Maximum ST segment depressionwas 0.13 mm less (p < 0.04) while on the fixed combination.The incidence of withdrawals and adverse effects was similaron both treatments.     

Monotherapy with amlodipine or atenolol versus their combination in stable angina pectoris

BACKGROUND: The basic cause of angina pectoris is imbalance between the metabolic needs of the myocardium and the capacity of the coronary circulation to deliver sufficient oxygenated blood to satisfy these needs. HYPOTHESIS: The study was undertaken to evaluate whether the effect of combined amlodipine and atenolol therapy on patients with stable angina pectoris and with ST-depression during exercise testing and 48-h ambulatory electrocardiographic monitoring is superior to that of either agent given alone. METHODS: Patients with stable angina pectoris and ST depression during exercise and ambulatory monitoring were randomized to receive amlodipine (n = 116) or atenolol (n = 116), or both (n = 119). All patients were also treated with short- and long-acting nitrates. The design was a double-blind, randomized, triple-arm parallel group study with 10 weeks of administration of the test medication. RESULTS: In terms of time to onset of ST depression > 1 mm, time to onset of angina, total exercise time, maximum achieved workload, and peak intensity of angina, amlodipine and atenolol alone were as effective as their combination. During ambulatory monitoring, atenolol was more effective than amlodipine regarding total time and number of ST-depression episodes, and as effective as the combined drugs. CONCLUSION: For individual patients with stable angina pectoris, combination of a beta blocker with a calcium antagonist is not necessarily more effective than either drug given alone.     

Exercise capacity after single and twice-daily doses of nicorandil in chronic stable angina pectoris

In a double-blind parallel group study, 46 patients with chronic stable angina were randomized, after a 2-week placebo washout period, to 1 of 3 treatment groups for an additional 2 weeks. Groups 1 and 2 received nicorandil (5 mg, N = 5; 10 mg, N = 10) twice daily, respectively, increasing to 10 and 20 mg (n = 20) twice daily after 1 week of treatment; group 3 continued to receive placebo. A symptom-limited Bruce protocol exercise test was performed before and 2 hours after the initial dose and, after 2 weeks of treatment, 2 and 12 hours after administration. The following parameters were measured: resting, peak exercise and recovery blood pressure and heart rate, exercise duration, time to onset of angina and time to 1 mm of ST-segment depression.

After initial dosing, there were significant increases in exercise duration (16%—n = 5, N = 10 vs −2% [placebo]) and time to onset of angina (20%, N = 5; 26%, N = 10 vs 5% [placebo]) (p < 0.05). Time to onset of 1 mm of ST-segment depression increased in the nicorandil-treated groups compared with that in the placebo group (27%, N = 5; 25%, N = 10 vs 8% [placebo]). Calculated total exercise work increased in both nicorandil groups compared with exercise work in the placebo group (30%, N = 5; 19%, N = 10 vs 3% [placebo]). A decrease in resting systolic blood pressure (12%) in the 10-mg group was the only significant alteration in the hemodynamic parameters. After 2 weeks of treatment there was a significant increase in time to onset of angina both 2 hours (38%, N = 10; 32%, N = 20 vs −2%) and 12 hours (23%—n = 10, N = 20 vs −2% [placebo]) (p < 0.05) after dose administration in both nicorandil groups compared with placebo group. Exercise duration, time to 1 mm of ST-segment depression and total exercise work increased in the nicorandil groups but these did not reach statistical significance. There was no significant change in the hemodynamic parameters at rest, peak exercise or recovery. Thus, nicorandil, 10 or 20 mg, administered twice daily improves exercise capacity both acutely and after chronic administration without significant alteration in blood pressure or heart rate.     

Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris

Nicorandil therapy was compared with placebo therapy in 11 patients with chronic stable angina pectoris. A computer-assisted treadmill exercise test was performed after administration of either 10 or 30 mg of nicorandil. Analysis of variance showed a significant difference among placebo and nicorandil treatments (p less than 0.01). Ten milligrams of nicorandil prolonged time to onset of ischemia 36% (p less than 0.05) but increased the exercise duration only 15%. Thirty milligrams of nicorandil prolonged time to onset of ischemia 82% (p less than 0.01) and exercise duration 45% (p less than 0.01). Both time to onset of ischemia and exercise duration increased progressively from the 10-mg to the 30-mg dose (p less than 0.05). Heart rate at rest was significantly higher and systolic pressure at rest significantly lower with 30 mg of nicorandil than with placebo. After administration of 30 mg of nicorandil there was a significant reduction in ST depression associated with a slight decrease in the double product at the end of Bruce stage 2 exercise. The peak double product was greater after administration of 30 mg of nicorandil than after placebo, indicating an increased myocardial oxygen supply to the ischemic area. The plasma concentration of nicorandil averaged 78 +/- 83 ng/ml with the 10 mg and 313 +/- 142 ng/ml with 30 mg. There was an increase in exercise duration of more than 1 minute in 8 of 9 patients who had plasma nicorandil concentrations greater than 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term use of oral nicorandil stabilizes coronary plaque in patients with stable angina pectoris

ObjectiveThe Impact of Nicorandil in Angina (IONA) trial demonstrated that the use of nicorandil, an anti-anginal drug, reduced future cardiovascular events in patients with stable angina. We hypothesized that nicorandil has beneficial effects on coronary arterial plaque characteristics and atherosclerogenesis.Methods and ResultsPreintervention intravascular ultrasound-virtual histology was performed prospectively in 65 consecutive patients with stable angina pectoris. There were no differences in coronary risk factors between the nicorandil (n = 16) and non-nicorandil (n = 49) groups. However, the nicorandil group demonstrated a larger %fibrous tissue (68 ± 10 vs. 62 ± 11%, P = 0.049) and a smaller %necrotic core tissue (11 ± 7 vs. 16 ± 10%, P = 0.049) compared with the non-nicorandil group. Multiple regression analysis showed that %necrotic core tissue (P = 0.045) was negatively and %fibrous tissue (P = 0.026) was positively associated with the use of nicorandil independent of statin use. We also analyzed the effect of nicorandil on atherosclerotic lesion formation in a mouse model of atherosclerosis. Lipid profiles were unaffected, but the area of atherosclerotic lesion and plaque necrosis were significantly reduced following 8-week nicorandil treatment in ApoE-deficient mice fed an atherogenic diet. Nicorandil significantly reduced the expression levels of endoplasmic reticulum stress markers, C/EBP homologous protein (CHOP) and glucose regulated protein/BiP (GRP78) in atherosclerotic lesions. Nicorandil significantly attenuated tunicamycin-induced CHOP upregulation in cultured THP-1 macrophages.ConclusionsNicorandil exerts its anti-atherogenic effect by mechanisms different from those of statins. Long-term nicorandil treatment is a potentially suitable second-line prevention therapy for patients with coronary artery disease.     

Bopindolol and atenolol in patients with stable angina pectoris. Double-blind randomized comparative trial

32 patients with stable angina and a positive symptom-limited exercise test (SLET) were investigated in a double-blind randomized trial in order to assess the therapeutic efficacy of bopindolol or atenolol on the incidence of angina pectoris and on angina pectoris threshold heart rate (ATHR). After a washout and placebo period of 2 weeks, each of the two drugs were applied in dosages of 0.5 mg bopindolol and 50 mg atenolol. The dosage was increased every month up to 2 mg bopindolol and 200 mg atenolol. At the end of every period, the patients were retested by SLET. After 3 months of active treatment, we noticed that the incidence of anginal attacks was lower in the bopindolol group (2.45 vs. 3.29). The resting heart rate was also lower in the bopindolol group (55.89 vs. 63.38). No statistical significance was found between the peak work rate, ATHR, exercise duration and S-T depression. The rate-pressure product was lower in the bopindolol group. We concluded from this that bopindolol and atenolol are active in decreasing the incidence of angina, the former being more effective. Exercise performance and cardiocirculatory parameters did not differ between the two groups.     

Dilitiazem in Comparison with metoprolol in stable angina pectoris

The efficacy of diltiazem in comparison with metoprolol in chornicstable angina was asessted in 33 male patients during a 15-weekblind cross-over study. After an initial two-week run-in period,baseline measuremens were made. Subsequently,the patients enereda cross-over study consisting of two six-week treatment periodswith diltiazem 240 mg (60 mg q.i.d.)or metoprol 200 mg (100mg b.i.d.).Dose adjustment to either 360 mg diltiazem(120t.i.d.)or400 mg metoprolol(200b.i.d.)was allowed two weeks after thestart of treatment. There was a one-week washout period betweenthe two treatment periods. Compared to baseline values both drugs reduced the number ofanginal attacks (diltiazem –55%,p=0.02; metoprolol –73%,P=0.01)andshowed improvement of the measured exercise variables(exerciseduration; diltiazem +16%,P<0.001;meoprolol +4%,P=NS; timeto angina:diltiazem +21%,P=0.02,metoprolol + 14%, P =NS;maximalST-depression: diltiazem +13%,P =NS,metoprolol +33%,P=0.002).Nosignificant change in LVEF was noticed.Both drugs reduced themean heart rate on Holter tape (diltiazem–11%,P=0.006;metoprolol–14%, P=0.004). No effects on conduction were noticed. Although at the borderline of significance, diltiazem increasedthe total exercise duration as compared to metoprolol (16 vs,4%,P=0.05). It is concluded that diltiazem improves exercisetolerance in patients with stable angina pectoris and appearsto be a safe and effective alternative to the beta-blockingagent metoprolol.Our findings underscore the value of diltiazemas a monotherapeutic drug for the treatment of stable angina.     

Effects of theophylline, atenolol and their combination on myocardial ischemia in stable angina pectoris

The effects of theophylline (400 mg twice a day), atenolol (50 mg twice a day) and their combination on myocardial ischemia were studied in 9 patients with stable angina pectoris in a randomized, single-blind, triple crossover trial. Placebo was administered to the patients during the run-in and the run-off periods. A treadmill exercise test and 24-hour ambulatory electrocardiographic monitoring were obtained at the end of each treatment period. Compared with placebo, theophylline significantly improved the time to onset of myocardial ischemia (1 mm of ST-segment depression) from 7.8 +/- 3.7 to 9.5 +/- 3.7 minutes (p less than 0.03) and the exercise duration from 9 +/- 3.4 to 10.1 +/- 3.5 minutes (p less than 0.04). During atenolol and during combination treatment, the time to the onset of ischemia and the exercise duration were similar (10.8 +/- 4.2 and 11.2 +/- 3.2 minutes, 11.2 +/- 3.6 and 11.5 +/- 3.2 minutes, respectively) and longer than during theophylline administration (p less than 0.05). Ambulatory electrocardiographic monitoring showed that, during theophylline administration, the heart rate was higher than during placebo throughout the 24 hours (p less than 0.05). During atenolol and during combination treatment the heart rate was similar and in both cases lower than during placebo (p less than 0.05). Compared with placebo, theophylline decreased the total ischemic time from 97 +/- 110 to 70 +/- 103 minutes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of atenolol in angina pectoris of effort

The effect of atenolol, a new cardioselective beta-adrenogenic blocking agent, was studied in 11 patients with angina of effort in a double-bind trial involving monitored exercise tolerance tests. The drug significantly reduced the heart rate, blood pressure and time-tension index. As a result, ST segment depression also diminished after treatment. Although working capacity, compared with controls, increased after atenolol, no difference was observed in this respect between the drug and placebo, suggesting the development of physiological tolerance to exercise. It is concluded that atenolol is useful in the prevention of angina pectoris, particularly in patients in whom there is associated arterial hypertension.     

Attenuation of anti-ischemic efficacy during chronic therapy with nicorandil in patients with stable angina pectoris

After 2 weeks of nicorandil therapy, time to ischemia on stress testing was significantly less than on day 1 and not different from placebo. These data are consistent with attenuation of the anti-ischemic effects of this drug and suggest that the potassium channel-opening properties do not compensate for development of attenuation to the nitrate component of nicorandil.     

Comparison of nicardipine and propranolol for chronic stable angina pectoris

In a double-blind, randomized, crossover clinical trial, a new calcium antagonist, nicardipine (90 mg/day in 3 divided doses), was compared with propranolol (120 mg/day in 3 divided doses) in 25 patients with chronic stable angina. The mean weekly frequency of angina episodes decreased from 7.8 +/- 1.2 (+/- standard error of the mean) with placebo to 3.8 +/- 1.2 with nicardipine treatment and 3.5 +/- 1 with propranolol treatment (p less than 0.001). With exercise testing, 5 patients receiving nicardipine and 3 receiving propranolol had no angina or ST-segment changes. Comparing paired samples of both drugs with placebo, significant improvement occurred in exercise duration (nicardipine, 1.3 +/- 0.3 minutes, p less than 0.001; propranolol, 1.0 +/- 0.4 minutes, p less than 0.01), time to onset of angina (nicardipine, 1.5 +/- 0.4 minutes, p less than 0.001; propranolol, 1.5 +/- 0.5 minutes, p less than 0.001), maximal ST-segment changes (nicardipine, 0.7 +/- 0.1 mm, p less than 0.01; propranolol, 0.06 +/- 0.1 mm, p less than 0.01) and time to 1 mm of ST depression (nicardipine, 2.5 +/- 0.4 minutes, p less than 0.01; propranolol, 2.0 +/- 0.3 minutes, p less than 0.01). One patient receiving propranolol and 2 receiving nicardipine withdrew from the study because of transient side effects. Mild side effects occurred in 10 patients receiving propranolol and 5 receiving nicardipine. Nicardipine proved to be safe and effective for patients with chronic stable angina; it had fewer side effects than propranolol in the doses used.     

Comparison of C-reactive protein and terminal complement complex in patients with unstable angina pectoris versus stable angina pectoris

Elevated C-reactive protein (CRP) can identify patients with coronary artery disease who are prone to future acute events. We investigated whether elevated CRP is related to the activation of the terminal complement cascade in 66 patients with unstable angina pectoris (UAP), in 45 patients with stable angina pectoris, and in 42 controls. CRP, additional acute phase reactants, the terminal complement complex (sC5b-9), leukocytes, and troponin T were measured. In 47 patients with UAP the CRP values were regarded as elevated (>0.3 mg/dl). In patients with UAP and elevated CRP, the plasma levels of sC5b-9 were markedly higher than in patients with UAP and lower CRP (245 +/- 14 vs 188 +/- 19 ng/ml, p <0.02) and in patients with stable angina pectoris with slightly (0.4 +/- 0.1 mg/dl) increased CRP (sC5b-9 173 +/- 21 vs 130 +/- 7 ng/ml [controls; p <0.05]). A further acute phase reaction was present only in patients with UAP and elevated CRP already on admission (p <0.01). sC5b-9 was not related to troponin release. Thus, elevated CRP levels are associated with activation of the plaque destabilizating terminal complement system in patients with UAP during the acute phase reaction. This may explain the prognostic value of CRP in acute coronary syndromes (ACS).     

Pathophysiology of stable angina pectoris

The pathophysiology of stable angina is discussed with respect to anatomic substrate, coronary and systemic hemodynamic mechanisms, the dynamic nature of coronary artery stenoses, and determinants of myocardial oxygen consumption. Cellular mechanisms involved in ischemia and the transduction of these changes into angina are also reviewed.     

稳定型与不稳定型心绞痛患者冠状动脉内超声的对比研究

目的　应用血管内超声对稳定与不稳定型心绞痛患者的冠状动脉病变进行对比分析。方法　 10 5例同时进行了选择性冠状动脉造影和血管内超声的患者 ,按心绞痛性质分为稳定型心绞痛组 (SA组 )和不稳定型心绞痛组 (UA组 ) ,比较两组患者冠状动脉狭窄程度、斑块形态和性质的差异。结果　两组冠状动脉造影显示的病变血管及狭窄程度差异无显著性 ;血管内超声显示 ,UA组病变以脂质斑块多见 ,SA组病变则以纤维斑块和钙化斑块更常见 ;SA组病变钙化的程度较UA组严重 ;UA组病变自发性内膜撕裂和血栓形成的比例明显高于SA组。结论　血管内超声显示 ,稳定型与不稳定型心绞痛患者的冠状动脉病变在形态和性质上存在明显差异。     

稳定型心绞痛患者口服尼可地尔对冠状动脉微循环阻力指数影响

目的探讨稳定型心绞痛患者服用尼可地尔治疗对冠状动脉微循环阻力指数(IMR)的影响。方法选取2014-03~2016-03该院收治的56例拟行介入术治疗的稳定型心绞痛患者,根据入院时间随机分为研究组和对照组,每组28例。两组入院后均给予常规药物治疗,对照组服用硝酸异山梨酯,研究组服用尼可地尔,均治疗4周,对治疗前后两组患者的IMR及临床效果进行比较分析。结果治疗后,研究组的IMR为(16.87±4.71),低于对照组的(26.21±8.61),差异有统计学意义(P0.05)。研究组显效14例,有效12例,无效2例。对照组显效9例,有效11例,无效8例。研究组疗效优于对照组(P0.05)。结论对稳定型心绞痛患者在常规用药基础上加服尼可地尔,可有效降低IMR,改善患者的冠状动脉微循环和心功能。