Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial. Quality of care for secondary prevention for patients with coronary heart disease: results of the Hastening the Effective Application of Research through Technology (HEART) trial. Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient. Physiologic and related behavioral outcomes from the Women's Lifestyle Heart Trial. Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease. Influence on lifestyle measures and five-year coronary risk by a comprehensive lifestyle intervention programme in patients with coronary heart disease. Randomised controlled trial of cardiac rehabilitation in elderly patients with heart failure. Cumulative meta-analysis of therapeutic trials for myocardial infarction. Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: results of the CEZAR study.
The use of repeated intravenous infusions of EDTA, which has become known as "chelation therapy," has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication.
                A double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal proportion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%).
                Chelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication. Effective therapies for reducing mortality rates in persons with coronary heart disease (CHD) remain underused. We report the results of an effectiveness trial of a quality improvement effort to increase the use of 3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors in patients with CHD in a network-model managed-care setting.
                Patients with CHD were identified by searching a claims database. The use of therapies was assessed by linkage with a pharmacy database. An intervention, consisting of a guideline summary, peer comparison performance feedback, and patient specific chart reminders was evaluated in a randomized, practice-based effectiveness trial.
                Data were available for >700 patients per year (1999-2002) in 131 practices. At baseline (1999), 55% of patients were receiving HMG CoA reductase inhibitors, 39% of patients were receiving beta-blockers, and 24% of patients were receiving ACE inhibitors. The use of all 3 types of medications increased steadily with time, with the exception of a decrease in the use of HMG CoA reductase inhibitors in the final year (2002). No difference in medication use was observed between randomized groups.
                The observed pattern of care supports the contention that the quality of outpatient care for secondary prevention of CHD improved from 1999 to 2002 in this setting. The basis for the inconsistent pattern of use of HMG CoA reductase inhibitors is not certain, but may relate to concerns about toxicity. Centralized mailings of guideline summaries, performance feedback reports, and chart reminders had no observable impact on quality of care in this setting. More intensive intervention may be required to improve the quality of outpatient care for the secondary prevention of CHD. In patients after renal transplantation functional arterial vessel wall properties are impaired. Whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have a sustained effect on endothelial function and arterial distensibility in patients after renal transplantation is not clear. The authors studied the effects of a long-term therapy with fluvastatin on large artery distensibility and flow-mediated vasodilation (FMD) in hypercholesterolemic patients after renal transplantation in a prospective, blinded, and randomized trial.
                Twenty-six patients who had undergone renal transplantation were assigned randomly to either fluvastatin, 40 mg/d (n = 13) or placebo (n = 13) and underwent follow-up for 3 years. At baseline and after 6, 12, and 36 months of treatment, carotid and brachial artery distensibility, endothelium-dependent FMD, and nitroglycerine-induced vasodilation (NMD) of the brachial artery were measured by a echo-tracking device.
                A significant decrease in total and low-density cholesterol was observed after 6, 12, and 36 months in patients treated with fluvastatin but not in the placebo group. FMD increased with fluvastatin from 4.6 +/- 2% to 12.4 +/- 2% after 12 months; this improvement was sustained with 13.4 +/- 3% after 36 months (P < 0.05). However, placebo did not alter FMD (P < 0.001 for trend difference between groups by analysis of covariance). Endothelium-independent NMD was similar in both groups at baseline and during therapy. Neither carotid nor brachial artery distensibility coefficients were altered by either treatment.
                HMG-CoA reductase inhibitor therapy over 3 years results in a significant and sustained improvement of endothelial function in hypercholesterolemic patients after renal transplantation. However, this is not accompanied by a beneficial effect on impaired large artery distensibility even after long-term therapy with fluvastatin. The Women's Lifestyle Heart Trial was a small (N = 28) randomized controlled trial to evaluate the effects of a comprehensive lifestyle self-management program (very low-fat vegetarian diet, stress-management training, exercise, group support, and smoking cessation) on reduction of cardiovascular risk factors in postmenopausal women with coronary heart disease (CHD). Women assigned to the treatment condition (Prime Time) participated in a week-long retreat followed by twice-weekly 4-hour meetings. Endpoints were program adherence; changes in lipid profiles, body mass, blood pressure, hypolipidemic and antihypertensive medications; and quality of life. Risk factor and psychosocial evaluations were conducted at baseline and at 4, 12, and 24 months. Repeated measures analyses of covariance revealed that the dietary, stress management, and physical activity changes made by intervention women were dramatic and lasting. There were significantly greater improvements in the Prime Time condition compared to the usual care control group on body mass, angina symptoms, and quality of life, and a tendency for a greater reduction in blood pressure-lowering medications. Similar patterns were seen in lipids, blood pressure, and lipid-lowering medications, but did not reach significance. These results demonstrate that postmenopausal CHD women can make lasting lifestyle changes, and that these changes may reduce the need for cardiac medications and improve CHD risk factors and quality of life. A prospective, randomized, controlled clinical trial in patients with coronary artery disease (CAD) and a concurrent physical disability evaluated the effects of a home exercise training program on cardiovascular function and blood lipids. Eighty-eight men between the ages of 42 and 72 years (mean 62) with documented CAD and a physical disability with functional use of > or = 2 extremities including 1 arm were randomized to either a 6-month home exercise training program using wheelchair ergometry or to a control group that received usual and customary care. Both groups received dietary instructions and were requested to follow a fat-controlled diet. Exercise test variables with echocardiography and blood lipids were measured at baseline and at 6 months. The home exercise training group significantly improved both peak exercise left ventricular ejection fraction (p = 0.007) and fractional shortening (p = 0.01) between baseline to 6 months, whereas the control group showed no significant changes. Exercise training effects of decreased resting heart rate (p = 0.03) and decreased peak rate pressure product (p = 0.03) were also found in the treatment group. No exercise-related cardiac complications occurred. Both groups significantly (p < or = 0.01) increased high-density lipoprotein cholesterol levels. These results indicate that physically disabled men with CAD can safely participate in a home exercise training program which may result in intrinsic cardiac benefits. The metabolic cost of activities of daily living imposed on this disabled population may also have a positive effect on high-density lipoprotein cholesterol levels. Lifestyle measures of coronary heart disease (CHD) prevention have been overshadowed by the efficacy of drug treatments. This is particularly the case in the setting of secondary prevention where the benefits of lipid lowering, anti-platelet and anti-hypertensive drugs have been emphasised in numerous trials. Lifestyle measures address several CHD risk factors at once and are generally free of serious side effects.
                The objective of the present study was to determine whether a comprehensive programme of lifestyle modification could favourably influence dietary and exercise habits in addition to smoking cessation over two years. In addition, an attempt was made to evaluate if this programme could favourably influence the five-year CHD-risk in the male population included in the study.
                A total of 197 patients with proven coronary heart disease were included and randomised to a lifestyle intervention programme or to usual care. Follow-up was after a period of two years.
                Intervention comprised a low fat diet, regular exercise, smoking cessation, psychosocial support and education, delivered by nurses on the rationale for pharmacological and lifestyle measures. Usual care comprised follow-up in the routine outpatient clinic. Both groups were given the same comprehensive medication according to recent guidelines.
                Patients in the lifestyle intervention group reduced the intake of saturated fat, sugar and cholesterol (P<0.001), increased their exercise level (P<0.01) and stopped smoking (P<0.05) when compared with the usual care group. A sub-analysis of the influence of five-year CHD calculated risk in males resulted in a relative risk reduction of 22% (95% confidence intervals 9-35). Although significant, this result must be interpreted with caution due to poor statistical power and reproducibility of the method.
                In the presence of modern drug treatments for secondary cardiovascular disease prevention it remains possible through a favourable diet, exercise and smoking cessation to show an additional reduction in the five-year risk for CHD in males. Heart failure, a condition predominantly affecting the elderly, represents an ever-increasing clinical and financial burden for the NHS. Cardiac rehabilitation, a service that incorporates patient education, exercise training and lifestyle modification, requires further evaluation in heart failure management.
                The aim of this study was to determine whether a cardiac rehabilitation programme improved on the outcomes of an outpatient heart failure clinic (standard care) for patients, over 60 years of age, with chronic heart failure.
                Two hundred patients (60-89 years, 66% male) with New York Heart Association (NYHA) II or III heart failure confirmed by echocardiography were randomised. Both standard care and experimental groups attended clinic with a cardiologist and specialist nurse every 8 weeks. Interventions included exercise prescription, education, dietetics, occupational therapy and psychosocial counselling. The main outcome measures were functional status (NYHA, 6-min walk), health-related quality of life (MLHF and EuroQol) and hospital admissions.
                There were significant improvements in MLHF and EuroQol scores, NYHA classification and 6-min walking distance (meters) at 24 weeks between the groups (p<0.001). The experimental group had fewer admissions (11 vs. 33, p<0.01) and spent fewer days in hospital (41 vs. 187, p<0.001).
                Cardiac rehabilitation, already widely established in the UK, offers an effective model of care for older patients with heart failure. The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta-analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction.
                We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction.
                An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratios, 0.74; 95 percent confidence interval, 0.59 to 0.92) was achieved in 1973, after only eight trials involving 2432 patients had been completed. The results of the 25 subsequent trials, which enrolled an additional 34,542 patients through 1988, had little or no effect on the odds ratio establishing efficacy, but simply narrowed the 95 percent confidence interval. In particular, two very large trials, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial in 1986 (11,712 patients) and the Second International Study of Infarct Survival trial in 1988 (17,187 patients) did not modify the already established evidence of efficacy. We used a similar approach to study the accumulating evidence of efficacy (or lack of efficacy) of 14 other therapies and preventive measures for myocardial infarction.
                Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy. Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction.
                Fifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80 mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent vasodilation (NMD), lipid, C-reactive protein (CRP) plasma concentrations and urinary 8-iso-prostaglandin F2alpha excretion were measured before and after treatment. Total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10. A80 caused significantly stronger improvement of FMD compared to A10E10 (absolute change FMD: A80+2.7+/-3.0% (post vs. pre p<0.001), A10E10+0.6+/-2.9% (post vs. pre p=0.25), A80 vs. A10E10 p=0.018). NMD was improved by A80 but not by A10E10 (absolute change NMD: A80+2.7+/-4.6%, A10E10+0.7+/-3.5%, p=0.12). Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostaglandin F2alpha excretion. There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group.
                The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms, LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD.
At present, there is insufficient evidence to decide on the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. This decision must be preceded by conducting randomized controlled trials that would include endpoints that show the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease.