Effect of Pravastatin on Outcomes after Cardiac Transplantation

Abstract

Hypercholesterolemia is common after cardiac transplantation and may contribute to the development of coronary vasculopathy. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be effective and safe in lowering cholesterol levels after cardiac transplantation. Cell-culture studies using inhibitors of HMG-CoA reductase have suggested an immunosuppressive effect. Early after transplantation, we randomly assigned consecutive patients to receive either pravastatin (47 patients) or no HMG-CoA reductase inhibitor (50 patients). Twelve months after transplantation, the pravastatin group had lower mean (±SD) cholesterol levels than the control group (193±36 vs. 248±49 mg per deciliter, P<0.001), less frequent cardiac rejection accompanied by hemodynamic compromise (3 vs. 14 patients, P = 0.005), better survival (94 percent vs. 78 percent, P = 0.025), and a lower incidence of coronary vasculopathy in the transplant as determined by angiography and at autopsy (3 vs. 10 patients, P = 0.049). There was no difference between the two groups in the incidence of mild or moderate episodes of cardiac rejection. In a subgroup of study patients, intracoronary ultrasound measurements at base line and one year after transplantation showed less progression in the pravastatin group in maximal intimal thickness (0.11±0.09 mm, vs. 0.23±0.16 mm in the control group; P = 0.002) and in the intimal index (0.05±0.03 vs. 0.10±0.10, P = 0.031). In a subgroup of patients, the cytotoxicity of natural killer cells was lower in the pravastatin group than in the control group (9.8 percent vs. 22.2 percent specific lysis, P = 0.014). After cardiac transplantation, pravastatin had beneficial effects on cholesterol levels, the incidence of rejection causing hemodynamic compromise, one-year survival, and the incidence of coronary vasculopathy.