Calcium blockers and atherosclerosis: lessons from the Stanford Transplant Coronary Artery Disease/Diltiazem Trial

Abstract

Accelerated coronary artery disease (TxCAD) in the long term heart transplant patient remains the major limitation to long term survival, with approximately 50% of patients developing an angiographic event of TxCAD by five years post-transplant. This accelerated vasculopathic process is believed to be due to chronic immune injury to the endothelium with coronary intimal proliferation developing rapidly. Subsequent lipid deposition develops in these proliferated areas, leading to a diffuse progressive occlusive CAD which can be seen on serial coronary arteriography as a progressive luminal narrowing. Based on multiple annual studies demonstrating a protective effect of calcium blockers in diet- or injury-induced vascular disease in animals, the authors undertook a randomized trial of diltiazem versus no calcium blocker begun early after heart transplantation in 1986. Serial quantitative coronary arteriographic measurements have demonstrated no significant change in the diltiazem group versus a decrease in mean coronary lumen diameter, from 2.41 +/- 0.27 to 2.19 +/- 0.28 mm, in the no calcium blocker group. These differences persisted at two and three years of follow-up. Freedom from CAD based on qualitative angiographic data confirmed this protective effect of diltiazem. These observations are supported by other reported retrospective studies of calcium blockers post-heart transplantation and in non-TxCAD. Therefore, calcium blockers appear to prevent the early coronary intimal proliferation in response to chronic immune injury, as well as the later lipid deposition. The cardiac transplant patient may serve as a useful model for study of antiatherosclerotic agents in humans.