Effect of pravastatin on outcomes after cardiac transplantation.
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.
Kobashigawa
J A
JA
Division of Cardiology, University of California at Los Angeles School of Medicine, USA.
Katznelson
S
S
Laks
H
H
Johnson
J A
JA
Yeatman
L
L
Wang
X M
XM
Chia
D
D
Terasaki
P I
PI
Sabad
A
A
Cogert
G A
GA
D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D015994:Incidence; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D015996:Survival Rate; D018084:Ultrasonography, Interventional
D002784:Cholesterol; D017035:Pravastatin