Acute heavy alcohol intake increases silent myocardial ischaemia in patients with stable angina pectoris.

OBJECTIVE: To evaluate the effect of acute alcohol ingestion on myocardial ischaemia in patients with coronary heart disease and stable angina. DESIGN: Randomised crossover study using fruit juice with and without ethanol. SETTING: Division of cardiology in a university hospital. PATIENTS: 20 patients with stable exertional angina and > or = 50% luminal diameter narrowing of at least one major coronary artery. INTERVENTIONS: Each patient was studied on two separate days, once after administration of 1.25 g of ethanol per kilogram of body weight diluted to 15% in juice, and once after an equivalent volume of juice; both tests were in the evening and lasted 90 minutes. The patients were scheduled to have 8 periods of walking for 10 min according to a time table. An ambulatory electrocardiogram and the occurrence of anginal attacks were recorded and blood pressure and blood ethanol concentration were measured until the next morning. RESULTS: The blood ethanol concentration (mean (SD)) rose to 28.8 mmol/l (1.3 (0.4)/1000). Alcohol raised the systolic blood pressure from 132 (16) to 141 (14) mm Hg (P < 0.05 compared with juice). The mean heart rate increased from 57 (7) to 64 (8) beats/min (P < 0.05) for 13 hours after ethanol ingestion compared with juice. The total duration of ischaemia during the ethanol test was 3.5 (median, range 0-80) min, compared with 0 (range 0-67) min for the juice test (P < 0.05). The difference resulted mainly from more silent ischaemia after ethanol ingestion (2.3 (0-80) v 0 (0-67) min; P < 0.05). The ST segment depression time integral increased during the ethanol test (4.4 (0-170) mm x min) relative to that during the juice test (0 (0-103) mm x min; P < 0.01) and especially during the following 13 hours after alcohol (3.5 (0-123) mm x min) compared with juice (0 (0-67) mm x min; P < 0.005). There were no changes in the number, duration, or ST segment depression time integral of the episodes of symptomatic angina, indicating that ethanol augmented the appearance of silent ischaemia. CONCLUSIONS: Acute heavy ethanol drinking aggravates myocardial ischaemia in patients with stable angina pectoris.     

Effect of benazepril on myocardial ischaemia in patients with chronic stable angina pectoris

The anti-ischaemic properties of benazepril, a non-sulfhydrylinhibitor of angiotensin-converting enzyme, were assessed in20 patients with chronic stable angina pectoris, by repeatedexercise tests and repeated 72-h ambulatory electrocardio-graphicmonitoring. The study was a double-blind, placebo-controlledcross-over; 11 patients received benazepril 10 mg b.i.d. andnine received 20 mg b.i.d. All patients had a positive treadmillstress test and at least three ischaemic episodes during 24h of ambulatory electrocardiographic monitoring. Benazepril at a dose of 10 mg b.i.d. did not improve the exerciseduration, the time taken to reach 1 mm ST depression. Similarfindings were observed during treatment with 20 mg b.i.d. Benazeprilat a dose of 10 mg b.i.d. was ineffective in improving ischaemicparameters during daily activities. However, among the ninepatients who received 20 mg b.i.d. the number of ischaemic episodeswas reduced from 142 to 103, and the total duration of ischaemiawas reduced from 1099 to 531 min. The number of weekly anginalattacks was reduced from 58 to 33, and the weekly sublingualnitroglycerin tablets consumption was reduced from 31 to 14.When the two doses (10 mg and 20 mg) were combined (N = 20),the number of ischaemic episodes was reduced from 314 to 260(P= 0.074), and the duration of ischaemia was reduced from 3453to 2514 min (P = 0.072).     

Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients

One hundred and fifty unselected patients with documented coronary artery disease were studied to establish the frequency and characteristics of silent myocardial ischaemia. Patients underwent ambulatory ST segment monitoring off all routine antianginal treatment (total 6264 hours) and exercise testing (n = 146). Ninety one patients (61%) had a total of 598 episodes of significant ST segment change, of which 446 (75%) were asymptomatic. Twenty seven patients (18%) had only painless episodes; 14 (9%) patients only painful episodes; 50 patients (33%) had both painless and painful episodes. The mean number of ST segment changes per day was 2.58 (1.95 silent); however, 11 patients (7%) had 50% of all silent episodes, and 48 patients (32%) had 91% of all silent episodes. Fifty nine patients (39%) had no ST segment changes on ambulatory monitoring, and 73 patients (49%) had no evidence of silent ischaemia. Episodes of silent ischaemia occurred with a similar circadian distribution to that of painful ischaemia, predominantly between 0730 and 1930. There was a similar mean rise in heart rate at the onset of both silent and painful episodes of ischaemia. Silent ischaemia was significantly more frequent in patients with three vessel disease than in those with single vessel disease, and was also significantly related to both time to 1 mm ST depression and maximal exercise duration on exercise testing. There was a highly significant relation between the mean number and duration of episodes of silent ischaemia in patients with positive exercise tests when compared with those with negative tests. No episode of ventricular tachycardia was recorded in association with silent ischaemic change.     

Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients.

One hundred and fifty unselected patients with documented coronary artery disease were studied to establish the frequency and characteristics of silent myocardial ischaemia. Patients underwent ambulatory ST segment monitoring off all routine antianginal treatment (total 6264 hours) and exercise testing (n = 146). Ninety one patients (61%) had a total of 598 episodes of significant ST segment change, of which 446 (75%) were asymptomatic. Twenty seven patients (18%) had only painless episodes; 14 (9%) patients only painful episodes; 50 patients (33%) had both painless and painful episodes. The mean number of ST segment changes per day was 2.58 (1.95 silent); however, 11 patients (7%) had 50% of all silent episodes, and 48 patients (32%) had 91% of all silent episodes. Fifty nine patients (39%) had no ST segment changes on ambulatory monitoring, and 73 patients (49%) had no evidence of silent ischaemia. Episodes of silent ischaemia occurred with a similar circadian distribution to that of painful ischaemia, predominantly between 0730 and 1930. There was a similar mean rise in heart rate at the onset of both silent and painful episodes of ischaemia. Silent ischaemia was significantly more frequent in patients with three vessel disease than in those with single vessel disease, and was also significantly related to both time to 1 mm ST depression and maximal exercise duration on exercise testing. There was a highly significant relation between the mean number and duration of episodes of silent ischaemia in patients with positive exercise tests when compared with those with negative tests. No episode of ventricular tachycardia was recorded in association with silent ischaemic change.     

Prognostic significance of silent myocardial ischemia in patients with unstable angina

Silent myocardial ischemia is common in unstable angina, but its prognostic significance is unknown. Fifty-two (42 with subsequent angiography) of 81 patients prospectively evaluated for unstable angina had ambulatory electrocardiographic (Holter) recordings analyzed by compact analog technique after they had received medical treatment (3 of the 52 had unanalyzable recordings and were excluded). From 1,103 hours of recordings, 298 ischemic episodes were identified, only 9% associated with angina. By Ridit analysis a significant correlation was found between the cumulative duration of transient myocardial ischemia and the number of diseased coronary vessels and indexes of proximal stenosis. During a 3 to 6 month follow-up period, there was one death and one patient was lost to follow-up among 20 patients without transient ischemia; in the group of 11 patients with a cumulative duration of transient ischemia less than 60 minutes/24 h, 7 were alive and well, 2 required coronary bypass surgery, 1 had coronary angioplasty for recurrence of angina and 1 was lost to follow-up. In the group of 18 patients with ischemia duration greater than 60 minutes/24 h, only 1 developed a stable angina pattern; 12 required coronary surgery (n = 11) or angioplasty (n = 1) and 5 developed myocardial infarction (2 died, 2 needed surgery for postinfarction angina and 1 recovered). A favorable clinical outcome occurred in only 6% of patients in the group with ischemia duration greater than 60 minutes/24 h; this rate was significantly lower (p less than 0.001) than that (70%) for the group with ischemia duration less than 60 minutes/24 h or that (95%) for the group without ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics and clinical significance of silent myocardial ischemia in unstable angina

The frequency and duration of transient myocardial ischemia on Holter recordings, analyzed by the compact analog technique, were determined in 41 patients (all men, mean age 54) with unstable angina (33 with angiographic evidence). There were 781 episodes of ischemia: 392 (50%) with ST-segment depression, 242 (31%) with ST elevation, 45 (6%) with ST elevation and depression in different leads, 70 (9%) with pseudonormalization of T waves and 32 (4%) with T-wave augmentation. Ventricular arrhythmias were associated with 18% of the episodes. The mean duration of ischemic episodes was 14 minutes (range 30 seconds to almost 12 hours); most were less than 5 minutes. Only 154 (20%) of the 781 episodes of ischemia were associated with pain. Conversely, 77 episodes of chest pain were not associated with electrocardiographic changes. Analysis of the temporal sequence of heart rate during the development of ischemia (analyzed in 415 episodes) showed that in only 43 (10%) the heart rate at the beginning of ischemia was significantly (greater than 6 beats/min) higher than that at 5 minutes (baseline) before the onset of ischemia. At the peak of the ischemic abnormality, the mean heart rate increase was 10% and returned to baseline at the end of the ischemic episode. The data indicate that 80% of ischemic episodes in unstable angina are silent and over 90% are not triggered by increases in heart rate; apparently increased oxygen demand is an uncommon cause of ischemia in unstable angina. Although most of the episodes were short-lived, some were extremely protracted without the development of myocardial infarction. The findings are of therapeutic significance.     

Prognosis in stable angina pectoris and silent myocardial ischemia

The results of current investigation suggest that a former clinical standby, namely, the presence or absence of angina, is no longer the principal prognostic factor for determining a patient's risk of cardiac events, including myocardial infarction. In a retrospective analysis, patients with chronic stable angina were compared on the basis of presence or absence of angina during ischemia detected by thallium imaging. Patients were similar in terms of risk factors, clinical characteristics and catheterization data. At 30 months of follow-up, the myocardial infarction rate was 22% in the silent group compared with 4% in the group with angina. Transient asymptomatic ischemia has prognostic value independent of other variables such as exercise stress testing or cardiac catheterization data. Future prognostic studies should be careful to include patient populations with similar characteristics; they also will need to provide protracted follow-up and utilize sensitive and reproducible diagnostic techniques.     

Clinical significance and management of silent myocardial ischemia in patients with angina pectoris and myocardial infarction

The present study was canued out to clarify the relationship between silent myocardial ischemia in patients with angina pectoris and onset of myocardial infarction, and the former's prognostic significance. The peak incidences of onset of myocardial infarction in patients were at 2 a.m., 9 a.m., 2 p.m., 8 p.m., and 9 p.m., and the peak onsets of transient silent myocardial ischemia in angina pectoris patients were at 9 a.m., 2 p.m., 8 p.m., and 9 p.m. Thus the most likely onset times were almost the same with both events. Of 169 patients with coronary artery disease admitted for treatment, 128 patients had no anginal attacks during follow-up and the remaining 41 had persistent angina despite adequate medical treatment. Holter monitoring electrocardiography was performed twice with the non-angina patients, during admission. Of these 128 patients, 54 showed no silent myocardial ischemia on either of the electrocardiographic recordings, 34 showed silent ischemia with the first Holter monitoring but not with the second one, and the remaining 41 showed silent myocardial ischemia on both tests. The subsequent incidences of "cardiac events" were 9.4%, 14.7%, and 36.6%, respectively for these three groups. Therefore, it is concluded that the presence of silent myocardial ischemia is closely related to onset of myocardial infarction and is an important prognostic factor in patients with coronary artery disease.     

Effect of nipradilol on silent myocardial ischemia,plasma beta-endorphin,and bradykinin in chronic stable angina

Hypothesis: This study was undertaken to investigate the effect of nipradilol on the total ischemic burden and on plasma levels of beta-endorphin and bradykinin. Methods: Sixteen patients with chronic stable angina were subjected to exercise treadmill testing and 24-h ambulatory electrocardiogram (ECG). Results: Nipradilol significantly decreased both mean heart rate and mean pressure rate product at submaximal and maximal exercise. It significantly improved exercise-induced maximal ST-segment depression from ?2.7 ± 0.5 mm to ?1.3 ± 0.6 mm (p<0.05) and reduced the number of leads with significant ST-segment depression (4.0 ± 1.2 vs. 2.0 ± 1.8, p<0.05). Silent ischemic episodes recorded in 24-h ambulatory ECG were significantly decreased by nipradilol administration, concomitantly with a decrement of mean heart rate and observed maximal heart rate. Patients with exercise-induced silent myocardial ischemia showed significantly increased plasma levels of beta-endorphin during both the placebo and nipradilol phases of the study. However, during the nipradilol phase, bradykinin did not change significantly at rest and at peak exercise. Conclusion: Nipradilol effectively controls exercise-induced myocardial ischemia and silent myocardial ischemic episodes, and does not influence the response of plasma levels of beta-enduced silent myocardial ischemia.     

Detection of silent myocardial ischemia in patients with angina using continuous electrocardiographic monitoring

In patients with effort angina, ST-segment depression is a reliable indicator of transient myocardial ischemia. Ambulatory electrocardiographic monitoring can detect episodes of ST-segment depression with and without chest pain in patients with coronary heart disease. This test provides valuable information about the presence, frequency, magnitude, and duration of transient myocardial ischemia and associated trigger factors.     

Lack of indication of myocardial cell damage after myocardial ischaemia in patients with severe stable angina.

To evaluate myocardial cell damage in relation to spontaneous and exercise-induced ischaemia, release of myoglobin, creatine kinase (CK) and its isoenzyme MB (CK-MB) into the serum was estimated in 10 patients with severe stable angina. All patients had a positive exercise test, significant stenosis of one or more of the main coronary arteries and more than five ischaemic attacks per week. ST-segment monitoring was performed for 36 h. During the last 24 h of that period (period A) serial blood samples were analysed for myoglobin, CK and CK-MB using sensitive assays. Three days later (period B) the patients performed an exercise test at 0815 h, with ST-segment monitoring and blood sampling carried out as described for period A. During period A, 47 ischaemic episodes (100% silent) with a total duration of 599 min were noted in four patients. Forty-seven ischaemic episodes (94% silent) with a total duration of 804 min, were observed in seven patients during period B. Release of myoglobin, CK, and CK-MB did not increase in relation either to spontaneous or exercise-induced ischaemia. Thus even frequent and prolonged episodes of transient myocardial ischaemia (symptomatic or asymptomatic) in patients with severe stable angina pectoris does not seem to cause irreversible myocardial damage.     

Effect of nipradilol on silent myocardial ischemia and heart rate variability in chronic stable angina

Purpose: Silent myocardial ischemic episodes as well as decreased heart rate variability (HRV) indices are associated with an unfavorable outcome in patients with coronary artery disease. Nipradilol, which is a non-selective beta-adrenergic and nitrate-like vasodilator anti-anginal agent developed in Japan, may ameliorate silent myocardial ischemia, while it also improves exercise tolerance and HRV indices in patients with chronic stable angina. Methods: To investigate the effect of nipradilol (6 mg daily) on silent myocardial ischemic episodes and HRV indices, and to study its effect on the relationship between them, 24 patients with chronic stable angina underwent exercise treadmill testing and a 24-hour ambulatory electrocardiogram (ECG). The study protocol utilized a single blind, 4-week placebo-controlled design. The HRV indices from ambulatory ECG included mean RR (ms), SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisted of total (ms, 0.01–1.00 Hz), low (ms, 0.04–0.15 Hz) and high (ms, 0.15–0.40 Hz) components. Results: Nipradilol significantly decreased the mean heart rate at submaximal and maximal exercise and the mean pressure rate product at submaximal and maximal exercise. It significantly improved exercise-induced maximal ST segment depression from –1.7 ± 0.6 mm to –1.1 ± 0.7 mm (p > 0.05). Silent myocardial ischemic episodes recorded during the 24-hour ambulatory ECG significantly decreased after nipradilol administration. Nipradilol also significantly influenced several HRV indices as well as the relationship between silent myocardial ischemic episodes and the HRV indices. Nipradilol significantly increased SD, rMSSD, pNN50, total spectra, low frequency spectra and high frequency spectra. In addition, nipradilol significantly decreased the LF/HF ratio from 1.7 (1.5–2.0) to 1.5 (1.3–1.8). These effects of nipradilol on HRV indices concomitantly occurred with the reduction in silent myocardial ischemic episodes. Conclusion: Nipradilol was found to effectively improve the episodes of silent myocardial ischemia as well as exercise-induced ischemia probably due to its beta-blocking properties and not nitrate-like actions. In addition, nipradilol also had a favorable effect on the HRV indices.     

Circadian variation in occurrence of transient overt and silent myocardial ischemia in chronic stable angina and comparison with Prinzmetal angina in men

Circadian periodicity was examined in 68 patients with chronic stable angina and in 9 patients with Prinzmetal angina. The frequency and duration of transient ischemic episodes were determined from analysis of 1 or more 24-hour Holter recordings by the compact analog technique. Ninety percent of the episodes in both syndromes were silent; 80% of the episodes of Prinzmetal angina were associated with ST-segment elevation and all episodes of chronic stable angina had ST-segment depression. Ischemic episodes were shorter (3 +/- 2 vs 18 +/- 23 minutes, p less than 0.0005) but more frequent (21 +/- 18 vs 6 +/- 4 per 24 hours, p less than 0.0001) in patients with Prinzmetal angina than in those with chronic stable angina. In patients with chronic stable angina, both silent and painful episodes had a peak occurrence in the morning and early afternoon hours (between 8 AM and 3 PM); the fewest episodes were between 1 AM and 5 AM. This distribution was not random by chi-square test (p less than 0.001). Cosinor analysis of ischemic episodes periodicity showed the acrophase at 1 PM, which was not different from that (3 PM) of the circadian rhythmicity for heart rate. In case of Prinzmetal angina, the acrophase of heart rate changes was at 5 PM, but a clear periodicity in the distribution of the ischemic episodes was not found. These differences in the circadian periodicity may reflect differences in the mechanism of ischemia in chronic stable angina and in Prinzmetal angina and are likely to be of therapeutic significance.     

Abrupt cessation of short-term continuous treatment with isosorbide dinitrate may cause a rebound increase in silent myocardial ischaemia in patients with stable angina pectoris.

OBJECTIVE: To examine by Holter electrocardiographic monitoring the effect of abruptly stopping nitrate treatment in patients with stable angina pectoris. PATIENTS: 12 men with confirmed ischaemic heart disease and stable exertional class 3 angina (Canadian). All had episodes of horizontal or down sloping ST segment depression during 24 hour electrocardiographic monitoring. All were nitrate responders. DESIGN: Each patient was given isosorbide dinitrate (10-30 mg four times a day) and placebo (four times a day) for three days in a randomised crossover trial. There was a washout period of 3-5 days between the two treatment periods. Holter monitoring was performed on the third day of isosorbide dinitrate and placebo administration and on the first day of their withdrawal. RESULTS: When treatment with isosorbide dinitrate was stopped there was a significant increase in the total number and duration of painless episodes of myocardial ischaemia. During placebo and isosorbide dinitrate administration 8 patients had episodes of painless myocardial ischaemia whereas after isosorbide dinitrate cessation they were recorded in all 12 patients. Episodes of silent myocardial ischaemia at rest appeared in 4 patients after isosorbide dinitrate withdrawal. CONCLUSION: Abrupt cessation of short-term continuous nitrate treatment in patients with severe angina may cause a rebound increase in myocardial ischaemia which is predominantly silent.     

The significance of human platelet-activating factor-acetylhydrolase in patients with chronic stable angina

BACKGROUND: Inflammatory reactions within coronary atherosclerotic plaques are increasingly thought to be crucial determinants of the clinical course in patients with coronary artery disease (CAD). Platelet-activating factor-acetylhydrolase (PAF-AH) is considered to reflect the ongoing inflammatory process in patients with CAD. Our objective was to determine the activity of PAF-AH in patients with stable angina and its correlations to lipoprotein levels and the inflammatory status of the patient. METHODS: Forty-five patients with documented CAD and stable angina and 20 controls were investigated for PAF-AH activity, lipoprotein levels, and peripheral neutrophil (PMN) activity. RESULTS: Patients were divided into two groups according to the values of PAF-AH activity (group 1: 250 IU/l). A correlation was observed between PAF-AH activity and LDL-C and HDL-C in controls and in all patients. The percentage of granulocytes generating intracellular O(2)(-) in unstimulated PMN was higher in group 2 patients than in group 1 patients and controls. The phagocytic activity of PMNs had an inverse correlation with PAF-AH in group 2. High intracellular O(2)(-) generation was coupled with low extracellular release of the anion and phagocytosis impairment in group 2. During the follow-up period, some of the patients in group 2 displayed a worsening of the clinical state and/or resting ECG changes. CONCLUSIONS: PAF-AH activity in patients with stable angina is correlated with hyperlipemia and a high PMN activation state, and it may be considered a potential predictor of vascular risk.     

The variable effects of angiotensin converting enzyme inhibition on myocardial ischaemia in chronic stable angina

The effect of angiotensin converting enzyme inhibition on myocardial ischaemia was studied in 12 normotensive patients with chronic stable angina and exercise induced ST segment depression. The study was randomised, double blind, placebo controlled, and crossover with treatment periods of two weeks. Enalapril was used to inhibit angiotensin converting enzyme. Assessment was by angina diaries and maximum symptom limited treadmill exercise tests. The results for the whole group showed a significant reduction in systolic blood pressure at rest and at peak exercise. Mean total exercise duration was 466 s (95% confidence interval 406 to 525) when the patients were taking placebo and 509 s (436 to 583) when they were taking enalapril. Four patients prolonged their total exercise time (mean 450 to mean 591 s) by more than 20%. Two patients, however, developed ischaemia earlier on exercise and reduced their total exercise duration (mean 490 to mean 390 s). Although angiotensin converting enzyme inhibition tended to reduce myocardial ischaemia in the group as a whole, some patients improved while others deteriorated. Thus the effects of enalapril are variable and this may have important implications when enalapril is used to treat heart failure in patients with underlying severe ischaemic heart disease.     

Optimal control of myocardial ischaemia: the benefit of a fixed combination of atenolol and nifedipine in patients with chronic stable angina

Objective—To study the effects on myocardial ischaemia of 50 mg of atenolol, 20 mg of slow release nifedipine, and their fixed combination given 12 hourly.

Design—A treadmill exercise test and 24 hour ambulatory electrocardiographic monitoring were carried out after a period of five days off treatment (control) and at the end of three weeks of each treatment period.

Patients—23 patients with stable angina pectoris, documented coronary artery disease, and a positive exercise test were randomised in a double blind, three way, cross over study.

Results—Compared with the control, nifedipine significantly induced an increase in resting heart rate of (mean (SEM)) 14 (2) beats/min whereas atenolol and the combination significantly reduced it by 24 (2) and 20 (1) beats/min respectively. The number of exercise tests rendered negative after each intervention was five for nifedipine, nine for atenolol, and 11 for the combination. Compared with the control the time to the start of myocardial ischaemia (1 mm ST segment depression) during exercise significantly increased by 3·2 (0·6) min after nifedipine, by 4·6 (0·4) min after atenolol, and by 4·6 (0·5) min after the combination; rate-pressure product (beats/min. mm Hg) at 1 mm ST segment depression increased by 2824 (970) after nifedipine but fell by 4436 (900) and 4501 (719) after atenolol and the combination. The weekly frequency of angina was reduced from a mean of five while taking nifedipine, to three while taking atenolol, and to two while taking the combination. The total ischaemic time during ambulatory monitoring was significantly reduced from 69 (17) min during control to 37·5 (9·8) min during nifedipine, to 15·6 (5·5) min during atenolol, and to 6·5 (2·7) min during the combination.

Conclusion—The undesirable effect of a high basal heart rate induced by nifedipine was neutralised by its combination with atenolol. Whereas atenolol and the combination were equally efficacious in controlling exercise induced ischaemia, the combination was more effective in reducing total ischaemic burden.

     

Angiotensin converting enzyme inhibition in chronic stable angina: effects on myocardial ischaemia and comparison with nifedipine.

OBJECTIVES--To determine the anti-ischaemic effects of a new angiotensin converting enzyme inhibitor, benazepril, compared with nifedipine, alone and in combination, in chronic stable angina caused by coronary artery disease. DESIGN--Placebo controlled, double blind, latin square design. SETTING--Regional cardiology service for a mixed urban and rural population. SUBJECTS--40 patients with stable exertional angina producing at least 1 mm ST segment depression on exercise test with the Bruce protocol. 34 patients completed all four phases of the trial. INTERVENTIONS--Each patient was treated with placebo, benazepril (10 mg twice daily), nifedipine retard (20 mg twice daily), and a combination of benazepril and nifedipine in the same doses, in random order for periods of two weeks. MAIN OUTCOME MEASURES AND RESULTS--Total duration of exercise was not increased by any treatment. Exercise time to the development of 1 mm ST segment depression was not significantly changed with benazepril alone or in combination with nifedipine but was increased with nifedipine from 4.18 (1.8) min to 4.99 (1.6) min (95% confidence interval (95% CI) 0.28 to 1.34; p < 0.05). There was a significant relation between increase in duration of exercise and resting renin concentration (r = 0.498; p < 0.01). Myocardial ischaemia during daily activity, as assessed by ambulatory electrocardiographic monitoring, was reduced by benazepril and by the benazepril and nifedipine combination. This was significant for total ischaemic burden (451(628) min v 231(408) min; 95% CI -398 to -41 min; p < 0.05) and maximal depth of ST segment depression (-2.47(1.2) mm v -2.16 mm; 95% CI 0.04 to 0.57; p < 0.05) for the combination and for maximal ST segment depth for benazepril monotherapy (-2.47 (1.2) mm v -1.96(1.2) mm; 95% CI 0.18 to 0.91; p < 0.05). Benazepril significantly altered the circadian rhythm of cardiac ischaemia, abolishing the peak ischaemic periods at 0700 to 1200 and 1700 to 2300 (p < 0.05). CONCLUSIONS--Benazepril, an angiotensin converting enzyme inhibitor, had a modest anti-ischaemic effect in effort angina, but this effect was not as pronounced as with nifedipine. The anti-ischaemic action was more noticeable in asymptomatic ischaemia during daily activity, whereas nifedipine had little effect on this aspect of myocardial ischaemia. The combination of benazepril and nifedipine reduced ischaemia of daily activity.