PRAVASTATIN REDUCES SERUM-CHOLESTEROL AND LOW-DENSITY-LIPOPROTEIN CONCENTRATIONS FOLLOWING PANCREAS TRANSPLANTATION

Hyperlipidemia is a significant risk factor for atherosclerotic vascular disease. We have shown previously that pancreas transplantation (PTX) improves but does not normalize lipids in most PTX recipients. We studied whether pravastatin was effective in treating 10 patients with elevated low density lipoprotein (LDL)-cholesterol (LDL-C) following PTX. Seven men and 3 women were studied. Six received combined kidney-pancreas transplantations, while 4 received PTX alone. Age at time of PTX was 37.2+/-2.2 years (mean +/- SEM), and 4 had established coronary artery disease before PTX. Mean cholesterol (C), LDL-C, triglycerides (TG), and high density lipoprotein (HDL)-cholesterol (HDL-C) were 236+/-12, 142+/-6, 222+/-50, and 49+/-4 mg/dl before PTX. The LDL to HDL ratio was 3.0+/-0.3. After PTX, excluding the first 45 days, mean C, LDL-C, and HDL-C increased to 278+/-10, 178+/-7, and 63+/-6 mg/dl (all P less than or equal to 0.05), respectively. TG, LDL to HDL ratio, and weight were unchanged. Pravastatin (11.7+/-0.8 mg/day, mean +/- SEM) was initiated 250+/-53 days after PTX. During therapy, C and LDL-C decreased on average to 231+/-10 and 134+/-8 mg/dl, respectively (both P<0.01), while HDL did not change. The decreases in C and LDL-C were unexplained by a decrease in weight, cyclosporine dose or concentration, or increase in serum creatinine. However, prednisone dose decreased over the same interval, so a contribution from this variable cannot be excluded. No evidence of toxicity was identified during therapy. This is one of the first reports demonstrating that pravastatin is a safe and effective treatment for elevated C and LDL-C in patients following PTX. However, pravastatin did not increase HDL or decrease TG, as observed in the nontransplantation setting. Whether pravastatin or any hypolipidemia therapy can prevent cardiovascular events or mortality following PTX remains to be established.