Search

Angina pectoris resulting from myocardial ischemia afflicts half of all patients with coronary heart disease (CHD). Chronic angina remains a major public health burden despite state-of-the-art therapies, and improvement in survival from myocardial infarction and CHD has only increased its prevalence. There is growing experimental and clinical evidence pointing to the anti-ischemic and anti-anginal properties of statins. Some data suggest that the degree of anti-ischemic efficacy of statins may be comparable to the current standard pharmacologic and mechanical strategies. The pleiotropic effects of statins are postulated to be primarily responsible for their anti-ischemic and anti-anginal properties. These include improvement of endothelial function, enhancement of the ischemic vasodilatory response, modulation of inflammation, and protection from ischemia-reperfusion injury. The anti-ischemic effects of statins further strengthen their role as a crucial component of the optimal medical therapy for CHD.

Beta adrenergic blockers have had a long history as frontline agents in hypertension therapy. They are the mainstay of treatment in ischemic heart disease, heart failure, high risk coronary artery disease and arrhythmias, as their importance in these compelling indications are well-established. However, the efficacy and relevance of beta blockers in the treatment of uncomplicated hypertension have been questioned because the traditional agents were deemed not atpar with drugs from other classes in terms of cardiovascular outcomes. Although atenolol and other traditional agent s have lost favor, the other cardioselective agents have been shown to be at least as efficacious in hypertension as the other classes of drugs. Their use in hypertension therapy should continue, especially in young and diabetic individuals where high sympathetic tone and high renin levels are the primary features. The newer-generation vasodilating beta blockers have favorable hemodynamic and metabolic properties, better side effect profile and improved efficacy in treating uncomplicated hypertension. With the advent of these new agents, the beta blocker class should remain as a viable first-line option in antihypertensive therapy.

Background: Patients with stable CHD who experience episodes of ischemia during routine daily activities are at increased risk of coronary events. Older patients are at a particularly high risk. Few trials have specifically investigated the effects of lipid-lowering therapy with statins in older patients., Methods: The SAGE trial is a prospective, randomized, double-blind, parallel-arm study enrolling men and women with stable CHD at 192 centers worldwide. Qualifying participants (aged 65-85 years; low-density lipoprotein cholesterol 100-250 mg/dL) have had at least 1 episode of myocardial ischemia with total ischemia duration >or=3 minutes on 48-hour ambulatory electrocardiographic (AECG) monitoring performed during routine daily activities. Participants have been randomized to either atorvastatin 80 mg/day (aggressive lipid lowering) or pravastatin 40 mg/day (moderate lipid lowering). The primary efficacy measure is the absolute change in the total duration of myocardial ischemic events on 48-hour AECG monitoring from baseline to month 12., Results: SAGE is fully enrolled and 893 patients have been randomized. The majority of the study participants are white (97%) men (69%). The mean age of the participants is 72 years. Most participants (94%) have a history of angina. Other high-risk patient groups included in the study are patients with hypertension (65%), patients with diabetes (23%), and patients with peripheral vascular disease (12%)., Conclusions: SAGE will evaluate the effect of aggressive versus moderate lipid lowering on the total duration of myocardial ischemia in older ambulatory patients with CHD. It is likely to provide valuable data on the benefits of statins in this patient population.

A deadly quartet of risk factors places diabetics at a particularly high risk for adverse cardiovascular events; these factors are hypertension, hyperlipidemia, hyperglycemia and hyperinsulinemia. A number of metabolic abnormalities are common to diabetes. Many of them, including dyslipidemia, have been linked to both insulin resistance and endothelial dysfunction. Several lines of evidence have led to the hypothesis that insulin resistance may be a key pathophysiological mechanism leading to endothelial dysfunction and atherosclerosis in patients with diabetes and possibly other illnesses. In both diabetic and nondiabetic populations, the common risk factors for coronary artery disease events are dyslipidemia, insulin resistance, obesity and high blood pressure. A number of strategies are recommended to prevent the potentially deadly consequences of these factors.

Coronary artery disease (CAD) is a leading cause of death and disability in the elderly. Several recent studies have shown that silent myocardial ischaemia (SMI) is a common manifestation of CAD, especially in the elderly. As many as 40% of elderly patients with no prior history of CAD may have underlying asymptomatic disease and up to 50% of elderly patients with known CAD might have evidence of SMI. The results of studies in elderly patients with CAD have also shown that SMI might exist despite antianginal therapy that is considered adequate for symptom control. In order to diagnose such residual SMI, the clinician would need to perform 24- to 48-hour Holter monitoring in the ambulatory setting while the patient is performing routine daily activities. Although a number of anti-ischaemic drugs have been evaluated for the treatment of SMI, available data suggest that beta-blocker given alone or in combination with a nitrate compound or calcium antagonist provides the best therapeutic choice. The long term benefit of SMI suppression in elderly patients has not been established. Future studies need to evaluate the clinical benefits of therapy given for SMI in the elderly.

A number of antianginal drugs and therapeutic strategies are now available for the treatment of patients with coronary artery disease (CAD) and myocardial ischemia. Of the available antianginal drugs, beta blockers appear to be most effective in suppressing myocardial ischemia. The superior anti-ischemic efficacy of beta blockers can be explained by their beneficial actions on hemodynamic parameters, vasomotion, and platelet function. Compared with other anti-ischemic drugs, beta blockers appear to be more efficacious in reducing the magnitude of myocardial ischemia during routine daily activities. In addition, the results of recent studies indicate that treatment with beta blockers not only suppresses myocardial ischemia, but also improves the clinical outcome in patients with CAD. These beneficial effects, along with the well-demonstrated cardioprotective effects of beta blockade in the postinfarction period, clearly suggest that this class of anti-ischemic drugs is an ideal therapeutic choice in most patients with CAD.

Myocardial ischemia occurs frequently during daily life and has a circadian pattern similar to that reported for myocardial infarction and sudden death. Because of the increased risk of myocardial ischemia in the morning hours, it has been suggested that the administration of anti-ischemic medication before bedtime may be more effective than the traditional morning dosing. This randomized, double-blind, placebo-controlled, crossover study evaluated the effects of 480-mg/day diltiazem (given either in the A.M. or the P.M.) on myocardial ischemia using ambulatory electrocardiographic monitoring in 68 patients with chronic stable angina and > or = 2 minutes of ischemia per 48 hours. During treatment with diltiazem, the duration and number of myocardial ischemic episodes were reduced by 45% (94 to 52 minutes, p <0.004) and by 40% (4.5 to 2.7 episodes, p <0.003), respectively. The duration and number of myocardial ischemic episodes during daytime (6 A.M. to 6 P.M.) hours were also reduced by 52% (74 to 36 minutes, p <0.002) and by 48% (3.1 to 1.6 episodes, p <0.001), respectively. There was no significant difference between A.M. and P.M. dosing. Morning ischemia (6 A.M. to noon), considered separately from daytime ischemia, was also significantly reduced by both A.M. and P.M. dosing regimens, with no difference between the regimens. The results of this study showed that both A.M. and P.M. dosing of long-acting diltiazem were equally effective in suppressing episodes of ambulatory myocardial ischemia at all times.

A clear understanding of the hemodynamic changes involved in the pathophysiologic process responsible for the genesis of myocardial ischemia is essential for the selection of the most appropriate anti-ischemic therapy. Based on the predominant mechanism responsible for myocardial ischemia, the therapeutic choice can vary widely.

Background: Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia., Methods and Results: A multicenter, randomized, double-blind, placebo-controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/- SD, 3.6 +/- 4.2 versus 1.7 +/- 4.6 episodes, P < .001) and average duration (30 +/- 3.3 versus 16.4 +/- 6.7 minutes, P < .001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4 +/- 4.6 to 3.1 +/- 6.0 episodes and 36.6 +/- 4.1 to 30 +/- 5.5 minutes). Event-free survival improved in atenolol-treated patients (P < .0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P = .001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P = .175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol., Conclusions: Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.

Although silent ischemia is common in patients with stable coronary artery disease (CAD), controversy surrounds the issue regarding the most appropriate method for detection. Routinely performed exercise tolerance testing provides important prognostic information. However, ambulatory electrocardiographic monitoring (AEM) has the distinct advantage of enabling evaluation of silent ischemia during daily life. Although numerous AEM studies have found a greater occurrence of silent ischemia than symptomatic ischemia in patients with stable angina pectoris, the independent prognostic value of AEM findings has not been definitively established. Several recent studies have addressed the question of whether AEM supplies additional information beyond that obtained from exercise testing. The results of these studies revealed that myocardial ischemia during daily life that is detected by AEM provides additional and independent prognostic information in patients with stable CAD who have evidence of ischemia during exercise testing.

The role of myocardial oxygen demand in the pathogenesis of silent ambulatory myocardial ischemia was evaluated by reviewing and assessing the methods and results of recent studies. The performance of simultaneous ambulatory electrocardiographic and blood pressure monitoring in 25 men with proven coronary artery disease (CAD) revealed significant increases in heart rate and blood pressure (p < 0.001) preceding most silent ischemic events. By plotting the mean heart rate obtained at 5-minute intervals during the 30 minutes before an ischemic event, the ischemic heart rate was shown to be significantly higher (95 +/- 15 vs 74 +/- 11 beats per minute [bpm]; p < 0.01) than the nonischemic heart rate. The evaluation of heart rate changes during ambulatory ischemia (in patients with CAD and ischemia induced by an exercise test using gradual work load increments) showed a significant heart rate increase (> 10 bpm) at 1-5 minutes preceding the onset of ST-segment depression. Heart rate increases during exercise testing according to the gradual work load increments of the National Institutes of Health protocol were compared with the heart rate preceding ischemic events during daily life monitored by ambulatory electrocardiography and were found to be closely related. In contrast, heart rate increases that occurred during exercise testing using the standard Bruce protocol were higher and correlated less with those preceding ischemia in daily life. Heart rate and blood pressure increased significantly in most silent ischemic episodes, indicating that increased myocardial oxygen demand plays a significant role in the pathogenesis of myocardial ischemia during daily life.