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[Calcium antagonists and development of the atheromatous plaque]
1Hôpital Cochin, service de cardiologie, Paris.
Abstract:
Transmembrane movements of calcium are implicated at different stages od the process of formation of the human atheromatous plaque. Calcium antagonist drugs have been shown, in several experimental models and in preliminary clinical trials, to slow the progression of atheromatous lesions. These pharmacodynamic effects could represent one of the mechanisms of the eventual long-term benefits of this pharmacological class. There are many techniques of assessing the atheromatous plaque in vivo but none of them represent a "criterion of substitution" establishing the confirmation of a therapeutic effect of a calcium antagonist drug or any other pharmacological class of drugs. The techniques applicable on a large scale are mainly ultrasonic evaluation of the non-coronary carotid and femoral arteries, providing information on the dimensions of the plaque rather than on its structure. The risk of progression of atheromatous plaques depends more on its structure, its histological and chemical composition, than on its dimensions, at least with regards to coronary lesions. In addition, the influence of treatment of atheromatous plaques of large arteries is not always representative of its effect on coronary lesions which are smaller and are submitted to very different conditions of perfusion. Only long-term studies of morbidity and mortality on large populations may demonstrate a beneficial effect on the progression of coronary artery disease itself. Techniques of evaluation of the atheromatous plaques have a role to play in ancilliary trials, satellites of these large scale studies of morbidity and mortality, but cannot be accepted as criteria of substitution.
Insights
Calcium channel blockers may slow atheromatous plaque progression. However, current imaging techniques cannot confirm therapeutic effects, necessitating long-term morbidity and mortality studies for definitive evidence.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Context:
- Atheromatous plaque formation involves transmembrane calcium movements.
- Calcium antagonist drugs show promise in slowing atheromatous lesion progression in preclinical and early clinical studies.
Purpose:
- To evaluate the role of calcium antagonists in managing atheromatous plaque progression.
- To assess the suitability of current in vivo plaque assessment techniques as surrogate endpoints for therapeutic efficacy.
Summary:
- Transmembrane calcium flux is integral to atheromatous plaque development.
- While calcium antagonists demonstrate potential in slowing lesion progression, current imaging methods (e.g., ultrasound of peripheral arteries) primarily measure plaque dimensions, not structure.
- Plaque structure, composition, and coronary lesion characteristics are critical for assessing disease progression and treatment response, which large-scale peripheral artery imaging may not accurately reflect.
Impact:
- Current imaging techniques are insufficient as surrogate markers for confirming the therapeutic benefits of calcium antagonists or other drug classes.
- Long-term morbidity and mortality studies in large populations are essential to establish the definitive benefits of interventions on coronary artery disease progression.
- Advanced plaque imaging techniques may serve as ancillary tools in large-scale trials but cannot replace robust clinical outcome data.