Efficacy of slow-release nifedipine on myocardial ischemic episodes in variant angina pectoris

To evaluate the efficacy of slow-release nifedipine (a single dose of 20 mg given at 10 P.M. or 2 doses of 20 mg at 10 P.M. and 6 A.M.) on ischemic episodes in patients with variant angina, a single-blind crossover study with ambulatory electrocardiographic monitoring was performed in 15 patients (13 men and 2 women, mean age 63 years). In all, there were 646 ischemic episodes detected with ambulatory electrocardiographic monitoring during the study period, and 618 episodes of them occurred during placebo periods with a circadian variation. Sixty-nine percent of the episodes in placebo periods were asymptomatic. The number of anginal attacks, nitroglycerin tablets taken, ST-segment elevation and the total ischemic duration significantly decreased during nifedipine therapy compared with results after the placebo therapy period, respectively (p less than 0.01 or 0.05). Twenty-eight ischemic episodes occurred during nifedipine therapy when the plasma level of nifedipine was low. Thus, asymptomatic ischemic episodes more frequently occur than symptomatic episodes and the administration of slow-release nifedipine is highly effective in suppressing not only symptomatic but also asymptomatic myocardial ischemia in patients with variant angina. The timing of the administration of slow-release nifedipine is an important factor in suppressing ischemic episodes.     

Effect of various antianginal agents on the frequency and duration of myocardial ischemic episodes in patients with stable angina pectoris]

The effects of verapamil, nifedipine, propranolol, and combinations of nifedipine+propranolol and nifedipine+verapamil were studied in 60 patients with stable angina pectoris. Verapamil was found to have a pronounced antianginal activity against all types of myocardial ischemia, whereas nifedipine relieved mainly painful ischemic episodes. By the end of 12-week therapy with propranolol, the agent lost its antiischemic effect in a third of patients, which was accompanied by an increase in the number and severity of silent ischemic episodes.     

Dissociation of exercise tolerance and total myocardial ischemic burden in chronic stable angina pectoris

Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.     

Effect of nifedipine on exercise tolerance in angina pectoris.

Nifedipine is a new antianginal drug, the calcium-antagonistic inhibitory action on excitation-contraction coupling apparently being so pronounced that, in therapeutic dosage, all other pharmacological properties are negligible. Its effect on exercise tolerance in angina was assessed by an exercise study involving 14 patients: single-stage exercise tests were chosen and the advantages of this are given. Our results suggest that the onset of action occurs after about 20 minutes, reaches a peak of activity at approximately one-half to two hours, and some effect may still be present at three hours. There was a significant improvement in exercise times with a mean rise of 50 per cent over placebo.     

Paradoxical effect of long-term treatment of nifedipine on total ischemic load in patients with stable angina pectoris.

In 50 patients with stable effort angina the effect of three drugs, metoprolol, nifedipine, and diltiazem was assessed by analyzing exercise stress test response and ambulatory ECG recordings. Both metoprolol and diltiazem caused a significant increase in time to ischemic threshold during exercise and a significant decrease of maximum ST-segment depression (during exercise and ambulatory ECG monitoring) and in the average number of daily ischemic episodes. Only metoprolol significantly reduced heart rate and rate-pressure product at the ischemic threshold during exercise. In the group of patients treated with nifedipine no significant improvement was observed in exercise tolerance or in number of ischemic episodes/24 h. Moreover, the subset of nonresponders in the two methods was larger than in the other two groups. In some of these patients a clearcut worsening of total ischemic load was observed, despite the control of symptoms. This adverse effect might be attributed to the different consequences of the vasodilatory effect of nifedipine on blood flow through stenosed vessels.     

Management of the total ischemic burden in angina pectoris

Recent reports suggest that neither the severity nor control of angina influences prognosis in patients with coronary heart disease. One possible explanation for such findings is that episodes of angina are only a small fraction of the daily ischemic episodes occurring in these patients. Silent episodes represent most of the ischemic burden in many patients with coronary disease who have positive exercise test results despite the absence of pain. Silent episodes also represent most of the ischemic burden in patients with either stable or unstable angina. Since silent episodes may have prognostic significance, a major goal of therapy should be the modification of both silent and painful ischemic episodes. Currently available pharmacotherapy has the potential to reduce the total ischemic burden caused by both painful and painless attacks and, thereby, alter prognosis.     

Effects of nifedipine on myocardial perfusion during exercise in chronic stable angina pectoris

Nifedipine may be effective in the treatment of stable angina by both decreasing myocardial oxygen demand and increasing myocardial oxygen supply. To determine the mechanism of action of nifedipine and its dose-response relation, 14 patients with stable angina were treated with nifedipine 10, 20 and 30 mg 4 times daily as single-agent therapy in a double-blind, randomized, placebo-controlled crossover trial. Treatment was continued for 1 week on each dose regimen and efficacy was determined using an exercise test at the end of each phase. Compared to placebo, a significant decrease of systolic blood pressure at peak exercise occurred with the nifedipine 20- and 30-mg regimens (p less than 0.05), accompanied by an increase in heart rate on the 10- and 20-mg regimens (p less than 0.005). There was no significant effect on the rate-pressure product compared to placebo at any exercise time on any of the nifedipine regimens. The times to onset of ST-segment depression and to angina were delayed significantly by all 3 dose regimens compared to placebo (p less than 0.02). There was a significant decrease in the magnitude of ST-segment depression at all exercise times by all dosage schedules of nifedipine compared with placebo (p less than 0.05), although there were no significant differences among the 3 dosage schedules. Data indicate that since nifedipine was effective in improving manifestations of myocardial ischemia during exercise without altering the double product at submaximal or maximal exercise, its beneficial mechanism of action may have been due to enhancing blood flow to ischemic zones or to favorably altering determinants of myocardial oxygen demand, which were not measured.     

Comparison of mortality and myocardial infarction rates in stable angina pectoris with and without ischemic episodes during daily activities

The prognostic significance of ischemic changes during daily activities was assessed in 56 patients with stable angina pectoris. All patients had positive results on the treadmill stress test and angiographic evidence of significant coronary artery disease. Forty-three (77%) had ischemic episodes on Holter monitoring during everyday activities. During the follow-up period (mean 2 years), there were 6 deaths and 6 myocardial infarctions among the 43 patients with ischemic episodes, compared with none among the 13 patients without such changes (p less than 0.03). All 14 patients referred for coronary bypass surgery belonged to the group with ischemic episodes (p less than 0.02). The extent of coronary disease, the treadmill test parameters, and the duration and frequency of ischemia during daily activities were identical in the patients with and without subsequent cardiac events. Patients with only symptomatic ischemic episodes or those with both silent and symptomatic episodes had a frequency of cardiac events similar to that of patients with only silent episodes. Thus, it seems that patients with stable angina pectoris and ischemic episodes during daily activities have a worse prognosis than patients free from such episodes.     

The prognostic importance of asymptomatic ischemic episodes in patients with unstable angina pectoris

Unstable angina pectoris is a high-risk ischemic disease which is characterized by recent onset of angina, a change in preexisting stable angina pattern or the occurrence of angina at rest. In a study of 70 patients with unstable angina on treatment with a triple drug regimen of nitrates, propranolol and nifedipine, 37 patients (53%) had 205 ischemic episodes, 90% of which were asymptomatic. 33 patients (47%) had no changes in the ST-segments. Between the two groups, there were no significant differences with respect to risk factors, medical treatment or coronary angiographic findings. Only the resting ejection fraction in the former group was slightly but significantly lower than in the latter group. At one month of follow-up seven patients had developed myocardial infarction, six of whom were in the group with silent ischemia. In 13 patients, due to inadequate success of medical treatment, bypass surgery or PTCA was performed; ten of these were from the group with silent ischemia. Of patients with silent ischemia, those with episodes totaling more than 60 minutes per 24 hours had the worst outcome. Multivariate analysis showed that, with respect to prognosis, the most important parameter was silent ischemia followed by angina pectoris.     

急性心肌梗塞前有无心绞痛对梗塞后心肌损害的影响

目的　探讨心绞痛对急性心肌梗塞（ＡＭＩ）后心肌损害的影响。方法　将８２例急性心肌梗塞患者分成心绞痛组（４８例）和无心绞痛组（３４例）,测定心脏肌酸磷酸激酶（ＣＰＫ）及其同功酶（ＣＫ－ＭＢ）、血清肌钙蛋白（ＣＴｎＴ）、Ｃ反应蛋白（ＣＲＰ）和尿微白蛋白分泌率（ＡＥＲ）变化。结果　心肌梗塞前有心绞痛者的ＣＰＫ、ＣＫ－ＭＢ、ＣＴｎＴ、ＣＲＰ和ＡＥＲ增高水平均较低,与心肌梗塞前无心绞痛患者比较,均有显著性差异（Ｐ＜ ０．０５）。结论　心绞痛对ＡＭＩ的心肌损害有明显保护作用。     

心绞痛患者528次缺血性ST段下移分析

83例心绞痛患者经24小时动态心电图监测到528次缺血性ST段下移,分析结果表明:1.在心绞痛患者缺血性ST段下移中,无症状性心肌缺血占75％,发生次数是有症状的3倍;2.缺血性ST段下移,85％与活动有关;3.缺血性ST段下移有明显的昼夜分布规律,上午6—10时为发作高峰,占全天总次数32％。提示在冠心病治疗中应重视包括无症状性心肌缺血在内的总缺血负荷,并结合缺血的昼夜分布规律调整给药时间。     

Sustained-release verapamil and nifedipine in exercise-induced angina pectoris.

In a randomised, double-blind, crossover study of oral sustained-release verapamil 360 mg o.d. ('SR-verapamil') and oral nifedipine 20 mg t.d.s. in 19 patients with chronic stable angina pectoris, significantly greater improvement from baseline was seen with SR-verapamil than with nifedipine. Mean exercise duration was 380 +/- 108 s with SR-verapamil and 343 +/- 130 s with nifedipine (P less than 0.05); mean time to onset of angina was 326 +/- 79 s with SR-verapamil and 239 +/- 79 s with nifedipine (P less than 0.01); median time to 1 mm ST depression was 252 s (range 114-579) with SR-verapamil and 182 s (range 84-582) with nifedipine (P less than 0.01); mean ST depression at maximum exercise was 1.65 +/- 0.56 mm with SR-verapamil and 2.17 +/- 0.98 mm with nifedipine (P less than 0.05). Ambulatory ECG recordings indicated a trend in favour of SR-verapamil (median ST-time integral 0.00 [range 0-24.16] mm h-1 with SR-verapamil, 1.15 [range 0-12.50] mm h-1 with nifedipine, not significant). Median glyceryl trinitrate consumption was significantly lower (P less than 0.05) with SR-verapamil (0.21; range 0-1.25 per day) than with nifedipine (0.31; range 0-1.32 per day), but there was no significant difference between angina attack frequency. Adverse events were reported by two patients with SR-verapamil and nine with nifedipine. Once-daily sustained-release verapamil 360 mg has a significantly better effect on exercise tolerance than nifedipine 20 mg t.d.s. and also appears to be better-tolerated.     

Efficacy of nifedipine therapy for refractory angina pectoris

Nifedipine is a calcium-channel blocking agent that has been effective for patients with angina pectoris when used as single-agent therapy and as part of a combination regimen with conventional antianginal therapy. However, the efficacy of nifedipine in patients with angina refractory to maximum tolerated conventional therapy has not been extensively studied. We present experience using nifedipine in the treatment of three distinct subsets of patients with refractory angina pectoris. One hundred twenty-seven patients with Prinzmetal's variant angina and documented coronary vasospasm were treated with nifedipine after experiencing an inadequate response to conventional therapy. Nifedipine, 40 to 160 mg daily, reduced the mean weekly rate of angina attacks from 16 to 2 (p < 0.001). In 63% of the patients complete control of angina attacks was achieved, and in 87% the frequency of angina was reduced by at least 50%. Nifedipine therapy was well tolerated, and the beneficial response persisted for the 9 months of follow-up. Nifedipine therapy was added to a second group of 11 consecutive patients with refractory episodes of recurrent rest ischemia following acute myocardial infarction. Prior to infarction all the patients had a history of exertional angina only; yet following the infarction, episodes of recurrent ischemia occurred at rest in spite of maximal medical management with beta blockers and/or nitrate preparations. With maximum tolerated conventional therapy the heart rate was lowered to a mean of 65 beats/min and the blood pressure to a mean of $\text{109}\text{70}\text{mm Hg}$. The episodes of rest ischemia were prevented in all but one patient by the addition of nifedipine (mean daily dose 60 mg, range 40 to 120 mg) without causing a change in heart rate or blood pressure. Two patients continued to have myocardial ischemia with minimal exertion, although resting pains were abolished, and they underwent coronary bypass surgery for rellef of exertional pain. Only one patient continued to have episodes of ischemia at rest, and bypass surgery was necessary for pain relief. The other eight patients have been managed medically for a mean of 5.4 months and have remained pain free on combined regimens of nifedipine, beta blockers, and/or nitrate preparations. The third group of patients treated with nifedipine is composed of 239 patients with severe classic exertional angina pectoris without a suspicion of superimposed coronary vasospasm. The anginal episodes in these patients were refractory to maximum tolerated conventional therapy; however, the addition of nifedipine (mean daily dose 60 mg, range 40 to 120 mg) reduced the mean weekly angina attack rate from 20.8 to 6.4 (p < 0.00001). Although only 11% of patients had complete prevention of angina during nifedipine therapy, a total of 70% experienced a reduction in angina frequency of at least 50%. We conclude that the addition of nifedipine therapy may provide further benefit for patients with angina pectoris refractory to maximum tolerated conventional therapy. Randomized, placebo-controlled studies are necessary to confirm the efficacy of nifedipine therapy in patients with refractory angina and to clarify the mechanism of the beneficial response.     

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.     

心肌梗死患者梗死部位存活心肌对心绞痛发作的影响

目的 :探讨心肌梗死 (MI)患者梗死部位存活心肌对心绞痛发作的影响。方法 :6 3例Q波MI患者分别行静息、硝酸甘油 (NTG)介入99mTc MIBI心肌灌注显像 ,评价梗死部位的存活心肌。结果 :① 6 3例MI患者的 5 6 7个心肌节段中 ,静息心肌显像共有 2 39个节段 (4 2 .15 % )灌注异常 ,含服NTG 1.0mg后介入心肌显像 2 39个节段中有 97个节段得到改善 ,占总异常的 4 0 .5 8% ;②不稳定型心绞痛者存活心肌检出率为 5 9.80 % ,稳定型心绞痛者为 2 9.2 9% ,两者比较差异有显著性意义 (P <0 .0 1)。结论 :①硝酸酯类药物介入显像可以提高严重灌注缺损区存活心肌的检出率 ;②MI后 ,有心绞痛发作 ,提示有较多的存活心肌     

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每日3次,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limn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显著意义(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.     

曲美他嗪对稳定型劳力性心绞痛患者 心肌缺血的影响

目的探讨曲美他嗪对冠心病(CHD)稳定型劳力性心绞痛患者心肌缺血的影响。方法选择经冠状动脉造影确诊的CHD稳定型劳力性心绞痛患者14例,在原有治疗不变的情况下,加用曲美他嗪治疗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心率及心率和收缩压的乘积;④运动诱发心绞痛发作所需的时间;⑤运动后ST段下降0.1mV所需的时间;⑥运动持续时间。结果患者每周心绞痛发作的次数及硝酸甘油片的用量均明显下降(P＜0.05);心率及心率和收缩压乘积轻度变化(P＞0.05);明显延长运动诱发心绞痛所需的时间及运动后ST段下降≥0.1mV所需的时间(P＜0.05)。结论曲美他嗪能改善运动诱发的心肌缺血,对CHD劳力性心绞痛患者有一定的疗效。     

Effect of nifedipine on exercise-induced left ventricular dysfunction and myocardial hypoperfusion in stable angina

To assess the effects of nifedipine on left ventricular function and regional myocardial perfusion, exercise radionuclide ventriculography was performed in 15 men (median age 59 years) and exercise thallium-201 scintigraphy was done in 11 of them, before and 90 minutes after the oral administration of 20 mg of nifedipine. All patients had stable angina and angiographically proved coronary artery disease without evidence of spasm. Exercise tolerance after administration of nifedipine increased from 343 ± 42 seconds to 471 ± 50 seconds (p < 0.01), whereas the peak exercise double product remained essentially unchanged (difference not significant). Ejection fraction improved significantly at rest (from 49 ± 3.6% to 52 ± 3.3%, p < 0.05) and at peak exercise (42 ± 3.3% to 47 ± 3.7%, p < 0.05). Nifedipine also resulted in an improved segmental wall motion score (4.3 ± 2.3 to 3.0 ± 2.3, p < 0.05; 0 = normal and 4 = worst degree of dysfunction). The ejection fraction increased by more than 5% in one third of the patients at rest, and in more than half of the patients at peak exercise. Improved exercise myocardial perfusion occurred in 5 of 11 patients (45%) and in 7 of 28 segments (25%) with reversible hypoperfusion. Thus, nifedipine produces significant improvement in global and regional left ventricular function in patients with coronary artery disease and stable angina. This may be accounted for, at least in part, by improvement in myocardial perfusion.