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Previous Volume 333:621-627 September 7, 1995 Number 10 Next

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ABSTRACT

Background 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.

Methods Early after transplantation, we randomly assigned consecutive patients to receive either pravastatin (47 patients) or no HMG-CoA reductase inhibitor (50 patients).

Results 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).

Conclusions 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.

Source Information

From the Divisions of Cardiology (J.A.K., S.K., J.A.J., L.Y., A.S., G.A.C., K.T., M.A.H., J.D.M., N.K., A.H.) and Cardiothoracic Surgery (H.L., X.M.W., D.C., P.I.T., D.C.D.), University of California at Los Angeles School of Medicine, Los Angeles; and Brigham and Women's Hospital, Boston (L.W.S.).

Address reprint requests to Dr. Kobashigawa at the UCLA Medical Center, CHS 47-123, Los Angeles, CA 90024.

Full Text of this Article

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