Diabetes is accompanied by more extensive atherosclerosis and inadequate compensatory remodeling. Accelerated plaque progression, despite use of medical therapies, supports the need to develop new antiatherosclerotic strategies in diabetic patients.
Aldosterone is an important mediator in the pathogenesis of heart failure, and increased plasma aldosterone levels are associated with a poor prognosis. Aldosterone-receptor blocking drugs can slow the progression of left ventricular remodeling and reduce the occurrence of sudden cardiac death. Two widely publicized clinical trials provide data demonstrating survival benefits with spironolactone and eplerenone in chronic and postinfarction heart failure. The publication of these trials has generated widespread enthusiasm for spironolactone and eplerenone, leading to the more frequent and sometimes unbridled use of these drugs in the medical community. We herein describe the likely mechanisms of action of aldosterone-receptor antagonists, discuss the existing clinical evidence supporting their use, and provide practical advice on their use in the management of patients with heart failure.
Increasing attention has been focused on the appropriate role of surrogate markers in the development of novel anti-atherosclerotic therapies. Technological advances in imaging modalities allow for visualisation of the entire arterial wall. Intravascular ultrasound (IVUS) has been increasingly employed to precisely quantify the extent of coronary atherosclerosis. Use of IVUS has provided a number of important insights into the natural history of atherosclerosis and the remodelling changes of the arterial wall in response to plaque accumulation. More recently, clinical trials have employed serial evaluations of arterial segments by IVUS to assess the impact of medical therapies.
Increasing use of established medical therapies presents a major challenge for the assessment of experimental antiatherosclerotic agents. The requirement to perform clinical trials with increasing numbers of subjects, followed for longer periods of time, creates a scenario that is largely prohibitive for the development of most new agents. Technologic advances in arterial wall imaging provide the opportunity to evaluate the impact of therapies on the natural history of atherosclerosis. The design and implementation of clinical trials that employ serial imaging of the arterial wall has become increasingly used in the development of new therapies to target atherosclerotic cardiovascular disease.
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