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Calcium channel blockers and coronary atherosclerosis: from the rabbit to the real world
1Division of Cardiology, Hartford Hospital, CT 06102-5037.
Abstract:
Many calcium channel blockers have been shown to retard the development of atherosclerosis in cholesterol-fed rabbits. The mechanisms that may contribute to this effect include stimulation of cholesteryl ester hydrolase activity in smooth muscle cells, amelioration of hypercholesterolemic-induced endothelial dysfunction, or inhibition of smooth muscle cell proliferation and migration. The effect of calcium channel blockers on the evolution of coronary atherosclerosis in humans has been assessed in three clinical trials. In the Montreal Heart Institute trial, nicardipine did not influence the overall rate of progression and regression; however, patients treated with nicardipine experienced significantly less progression of minimal lesions, defined as stenoses of less than or equal to 20% severity. In the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT), nifedipine had no effect on overall progression and regression but, by one method of analysis, reduced the rate of appearance of new coronary lesions. In a preliminary report, diltiazem prevented the development of coronary atherosclerosis in heart transplant recipients. These studies indicate that calcium channel blockers retard the development of early atherosclerosis not only in animal models but also in human coronary arteries. Other studies recently completed or now under way will help to clarify the clinical role of calcium channel blockers in antiatherosclerotic therapy.
Insights
Calcium channel blockers show promise in slowing early atherosclerosis development in both animal models and human coronary arteries. Clinical trials suggest these drugs may particularly benefit patients with minimal arterial lesions.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Atherosclerosis Research
Background:
- Calcium channel blockers (CCBs) have demonstrated anti-atherosclerotic effects in animal models.
- Potential mechanisms include effects on smooth muscle cells and endothelial function.
- Previous research suggests CCBs may influence the development of atherosclerosis.
Purpose of the Study:
- To evaluate the impact of CCBs on the progression of coronary atherosclerosis in human clinical trials.
- To assess the anti-atherosclerotic potential of specific CCBs like nicardipine, nifedipine, and diltiazem.
Main Methods:
- Analysis of data from three clinical trials investigating CCBs and coronary atherosclerosis.
- Evaluation of lesion progression, regression, and the appearance of new lesions in treated patients.
- Review of preliminary data from heart transplant recipients treated with diltiazem.
Main Results:
- Nicardipine showed reduced progression of minimal coronary lesions (≤20% stenosis).
- Nifedipine (in the INTACT trial) did not affect overall progression but potentially reduced new lesion formation.
- Diltiazem demonstrated a preventive effect on atherosclerosis development in heart transplant recipients.
Conclusions:
- CCBs appear to retard the development of early atherosclerosis in human coronary arteries, consistent with animal studies.
- These findings suggest a potential role for CCBs in anti-atherosclerotic therapy, particularly for early-stage disease.
- Further research is ongoing to fully elucidate the clinical utility of CCBs in managing atherosclerosis.