Impact of diltiazem administration and cyclosporine levels on the incidence of acute rejection in heart transplant patients

Abstract

To identify the clinical factors associated with acute rejection (AR) in the first year after heart transplantation (HT), we analysed 112 patients. All patients received OKT3 and standard triple-drug therapy. We analysed the following variables to determine their relationship with AR: age and gender, panel-reactive antibodies, HLA-DR mismatch, use of Sandimmune vs Neoral, diltiazem administration, and cyclosporine levels in week 2 and months 1, 2, and 3 after HT. Fifty-two patients had no AR and 49 had at least one episode. The variables independently associated with absence of AR were diltiazem administration (odds ratio 0.306, confidence limit 0.102-0.921) and cyclosporine level in the first month after HT (odds ratio 0.996, confidence limit 0.992-0.999). Furthermore, a cyclosporine level greater than 362 ng/ml in the first month predicted the absence of AR. In conclusion, a cyclosporine level greater than 362 ng/ml and diltiazem administration in the first month after HT reduce AR during the first year. Both cyclosporine level and diltiazem show a large and independent protective effect.

Management of hypertension in heart transplant recipients: an ongoing conundrum

“…Early studies showed that the use of diltiazem reduced the narrowing of coronary vascular lumen in transplant patients, especially during the first year posttransplant [22]. In addition to their antihypertensive properties, CCB use has been linked to reduce the risk of acute rejection partly by increasing CNI's levels [23].…”

“…Moreover, hypertension is a common adverse effect of steroids and calcineurin inhibitors due to their ability to alter vascular tone and activate the sympathetic system, resulting in an increased tendency for salt and water retention through their impact on the distal convoluted tubule [38]. While key to managing hypertension involves appropriately weaning steroids and adjusting calcineurin inhibitors, CCB and thiazides diuretics are commonly used antihypertensives [21 ▪▪ ,23].…”

Inhibitors of Calcineurin

“…Some transplant centers have used the drug interactions between cyclosporine and drugs such as ketoconazole, fluconazole, or diltiazem for their cyclosporine-sparing effects. 37,38 Although controversial, this practice substantially reduces the cyclosporine acquisition cost and in some cases allows for once-daily dosing. The safety and efficacy of such regimens have been established on a limited basis.…”