Effect of Pravastatin on Outcomes after Cardiac Transplantation
Jon A. Kobashigawa, M.D., Steven Katznelson, M.D., Hillel Laks, M.D., Jay A. Johnson, M.D., Lawrence Yeatman, M.D., Xiu Ming Wang, M.D., David Chia, Ph.D., Paul I. Terasaki, Ph.D., Alejandro Sabad, B.A., Gregory A. Cogert, Kevin Trosian, B.A., Michele A. Hamilton, M.D., Jaime D. Moriguchi, M.D., Nobuyuki Kawata, M.D., Antoine Hage, M.D., Davis C. Drinkwater, M.D., and Lynne W. Stevenson, M.D.
Background Hypercholesterolemia is common after cardiac transplantationand 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 safein lowering cholesterol levels after cardiac transplantation.Cell-culture studies using inhibitors of HMG-CoA reductase havesuggested an immunosuppressive effect.
Methods Early after transplantation, we randomly assigned consecutivepatients to receive either pravastatin (47 patients) or no HMG-CoAreductase inhibitor (50 patients).
Results Twelve months after transplantation, the pravastatingroup had lower mean (±SD) cholesterol levels than thecontrol group (193±36 vs. 248±49 mg per deciliter,P<0.001), less frequent cardiac rejection accompanied byhemodynamic compromise (3 vs. 14 patients, P = 0.005), bettersurvival (94 percent vs. 78 percent, P = 0.025), and a lowerincidence of coronary vasculopathy in the transplant as determinedby angiography and at autopsy (3 vs. 10 patients, P = 0.049).There was no difference between the two groups in the incidenceof mild or moderate episodes of cardiac rejection. In a subgroupof study patients, intracoronary ultrasound measurements atbase line and one year after transplantation showed less progressionin the pravastatin group in maximal intimal thickness (0.11±0.09mm, 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 naturalkiller cells was lower in the pravastatin group than in thecontrol group (9.8 percent vs. 22.2 percent specific lysis,P = 0.014).
Conclusions After cardiac transplantation, pravastatin had beneficialeffects on cholesterol levels, the incidence of rejection causinghemodynamic compromise, one-year survival, and the incidenceof 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.
Drugs in Cardiac Transplantation
Ballantyne C. M., von Moltke L. L., Greenblatt D. J., Kobashigawa J., Keogh A. M., Spratt P., Valantine H. A.
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N Engl J Med 1996;
334:400-402, Feb 8, 1996.
Correspondence
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