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Biomedical subjects

Alan B Miller

Publications and source records attributed to Alan B Miller.

10 recordsLinked to original sources

Cardiovascular risk factors in hypertension: rationale and design of studies to investigate the effects of controlled-release carvedilol on regression of left ventricular hypertrophy and lipid profile.

Patients at high risk for hypertension may require several therapeutic agents to lower their blood pressure to guideline-recommended targets. Some antihypertensive agents are more effective than others in protecting against cardiovascular morbidity and mortality. Numerous beta-blocking agents have been approved by the US Food and Drug Administration (FDA) for the treatment of hypertension. Previous trials have demonstrated that although all beta-blockers effectively reduce blood pressure, there are differences in how they affect various metabolic factors. In 2 trials, a novel controlled-release (CR) formulation of carvedilol will be tested against other selective beta-blockers to determine whether differences exist in their individual effects on cardiovascular risk factors. These will be the first head-to-head trials using carvedilol CR to determine whether the differing pharmacologic actions among beta-blockers result in varying effects on cardiovascular risk factors.

Adrenergic beta-Antagonists↗

The effect of statins in heart failure: beyond its cholesterol-lowering effect.

BACKGROUND: Statins known as 3-hydroxyl-3-methyl-glutaryl-coenzyme A (HMG-CoA) are designed to lower plasma cholesterol levels. They are used to treat hypercholesterolemia, ischemic heart disease patients, heart transplant recipients, in prevention of Alzheimer's dementia, multiple sclerosis, and have also been shown to reduce cancer risk. METHODS AND RESULTS: The idea of statin treatment in chronic heart failure is not well established. It has been shown to be beneficial in patients with ischemic heart disease with heart failure. Emerging trends show their usefulness in patients with nonischemic heart failure. Statins exhibit pleiotropic effects in stabilizing the atherosclerotic plaques, improvement of endothelial function, inhibition of cell migration and proliferation, and reduction of inflammation and oxidative stress. They also improve autonomic function with an increased parasympathetic drive, downregulate the angiotensin II type I receptors, and induce angiogenesis. CONCLUSION: This article is a review on the current knowledge on statin use in heart failure.

Anticholesteremic Agents↗

Congestive heart failure and atrial fibrillation: rhythm versus rate control.

BACKGROUND: The incidence both of heart failure and atrial fibrillation is steadily increasing in the United States' population, and these conditions frequently coexist in the same patient. It is likely that the onset of one of these disorders leads to the onset and propagation of the other through multiple mechanisms. Several studies have investigated the prognosis of patients with both conditions, but a definitive conclusion regarding outcomes such as mortality and quality of life has yet to be determined. METHODS AND RESULTS: Evidence demonstrating the improvement of left ventricular function and other hemodynamic parameters with the restoration and maintenance of sinus rhythm does exist. beta-blockade, angiotensin-converting enzyme inhibition, and aldosterone antagonism have been shown to improve survival in patients with heart failure. However, the efficacy of these therapies in patients with coexisting atrial fibrillation has not been adequately assessed. Furthermore, these therapies do not directly address the issue of rhythm management. The use of several antiarrhythmic medications and device therapy is becoming more frequent in the management of this subset of patients. Recent investigations of antiarrhythmic treatment have assessed outcomes such as survival, quality of life, exercise tolerance, and maintenance of sinus rhythm. Data from these studies suggest that antiarrhythmic therapy may be efficacious in such patients. Device therapy is another alternative which has been demonstrated to be at least as beneficial as medical therapy. CONCLUSION: Both retrospective and prospective studies of antiarrhythmic therapy and device therapy have demonstrated promising results. Several studies are ongoing and will provide more insight into the management of such patients.

Adrenergic beta-Antagonists↗

Importance of echocardiography in patients with severe nonischemic heart failure: the second Prospective Randomized Amlodipine Survival Evaluation (PRAISE-2) echocardiographic study.

BACKGROUND: Echocardiography is used commonly in clinical practice when caring for patients with heart failure. It is unknown whether the presence of certain findings provides an incremental ability to predict survival beyond the use of baseline clinical findings alone. The second PRAISE-2 echocardiographic study was prospectively designed to identify echocardiographic predictors of survival among patients with nonischemic cardiomyopathy and heart failure and to determine if components of the echocardiographic examination add prognostic information to baseline demographic and clinical information. METHODS: One hundred patients participated in the second Prospective Randomized Amlodipine Survival Evaluation Study (PRAISE-2) echocardiographic study; of these, 93 had full and interpretable echocardiographic examinations. Cox proportional hazards modeling was used to assess the relation between various characteristics and survival as well as to assess the incremental prognostic information gained by echocardiography beyond the clinical examination. RESULTS: Seven of 10 routine echocardiographic measures were significantly associated with death. These included mitral regurgitation (hazard ratio [HR], 2.31; 95% CI, 1.02, 5.27), left ventricular ejection fraction <20% (HR, 2.59; 95% CI, 1.14, 5.88), restrictive left ventricular filling pattern (HR, 2.37; 95% CI, 1.05, 5.32), and peak D velocity (HR, 1.62; 95% CI, 0.38, 0.87). The only statistically significant clinical predictor of survival was dyspnea at rest. The addition any of several echocardiographic parameters to baseline clinical information significantly improved the ability to predict survival. CONCLUSIONS: Several readily available echocardiographic parameters are predictive of death and when added to clinical examination findings significantly improve the ability to determine prognosis among patients with nonischemic cardiomyopathy and heart failure.

Amlodipine↗

Agents that stabilise atherosclerotic plaque.

The concept of plaque stabilisation was developed to explain how medications could decrease adverse coronary events without a substantial reduction in the regression of atherosclerosis. With this concept, a comprehensive view of atherosclerosis is now appreciated. A number of imaging modalities are employed to study atherosclerosis; most identify luminal diameter or stenosis, wall thickness and plaque volume. A number of antiatherosclerotic agents have been studied as well to prove this hypothesis. However, the ultimate goal of medical treatment is to cure or prevent diseases caused by atherosclerosis.

Adrenergic beta-Antagonists↗

Anticoagulation in patients with dilated cardiomyopathy and sinus rhythm: a critical literature review.

BACKGROUND: The risk of thromboembolism in chronic heart failure and the risk-to-benefit ratio of anticoagulation in this population are poorly defined. METHODS AND RESULTS: A PubMed/MEDLINE search of published trials was performed. Twenty-four studies were identified after exclusion of individual case reports. All studies were prospective or retrospective observational reports, either independent studies or secondary analyses of prospective clinical trials in patients with heart failure. Prevalence estimates ranged of thromboemboli ranged from 3% to 50% and incidence estimates ranged from 1.5 to 3.5/100 patient-years. Although no randomized data of therapeutic anticoagulation were identified, a secondary analysis of one study suggested event reduction in patients receiving warfarin anticoagulation; other studies failed to suggest such benefit. Overall bleeding estimates in warfarin-treated patients ranged from 2.3 to 6.8/100 patient-years. Intracranial hemorrhage rates were 0.62 to 0.9/100 patient-years but increased with age. Only one study suggested that aspirin was beneficial in reducing clinically significant emboli. CONCLUSIONS: Although patients with chronic heart failure and left ventricular dilation have a higher risk of thromboembolism, data are insufficient to recommend warfarin or aspirin prophylaxis in the absence of additional indications for such therapy.

Anticoagulants↗

Diuretic resistance predicts mortality in patients with advanced heart failure.

BACKGROUND: In patients with chronic heart failure (CHF), diuretic requirements increase as the disease progresses. Because diuretic resistance can be overcome with escalating doses, the evaluation of CHF severity and prognosis may be incomplete without considering the intensity of therapy. METHODS: The prognostic importance of diuretic resistance (as evidenced by a high-dose requirement) was retrospectively evaluated in 1153 patients with advanced CHF who were enrolled in the Prospective Randomized Amlodipine Survival Evaluation (PRAISE). The relation of loop diuretic and angiotensin-converting enzyme inhibitor doses (defined by their median values) and other baseline characteristics to total and cause-specific mortality was determined by proportion hazards regression. RESULTS: High diuretic doses were independently associated with mortality, sudden death, and pump failure death (adjusted hazard ratios [HRs] 1.37 [P =.004], 1.39 [P =.042], and 1.51 [P =.034], respectively). Use of metolazone was an independent predictor of total mortality (adjusted HR = 1.37, P =.016) but not of cause-specific mortality. Low angiotensin-converting enzyme inhibitor dose was an independent predictor of pump failure death (adjusted HR = 2.21, P =.0005). Unadjusted mortality risks of congestion and its treatment were additive and comparable to those of established risk factors. CONCLUSIONS: The independent association of high diuretic doses with mortality suggests that diuretic resistance should be considered an indicator of prognosis in patients with chronic CHF. These retrospective observations do not establish harm or rule out a long-term benefit of diuretics in CHF, because selection bias may entirely explain the relation of prescribed therapy to death.

Aged↗

Renin-angiotensin system antagonism and lipid-lowering therapy in cardiovascular risk management.

The renin-angiotensin system (RAS) and dyslipidaemia have been shown to be involved in the genesis and progression of atherosclerosis. Manipulation of the RAS has been effective in modifying human coronary artery disease progression. Similarly, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors or statins have been shown to reduce cholesterol and lower cardiovascular events in primary and secondary prevention trials in coronary artery disease. In addition to their primary mode of action, statins and blockers of the RAS possess common additional properties that include restoration of endothelial activity and inhibition of cellular proliferation. This article reviews the current data on the common properties of these classes of drugs in which the beneficial effects extend beyond their antihypertensive and lipid-lowering properties.

Antihypertensive Agents↗