Question

• 2 year old male with a cardiac transplant has hyperlidpidemia secondary to immunosuppressive regimen. In pediatric heart transplant patients, how will treatment with HMG CoA reductase inhibitors versus no treatment affect his course and prognosis?

Clinical Bottom Lines

1. It is still not clear whether pravastatin will improve long-term graft survival, but it may be logical to infer that reducing lipid levels should improve health of coronary vasculature in any patient. Further followup will be required to actually prove prolongation of graft life.
   
2. Pravastatin given to 22 pediatric heart transplant patients with hyperlipidemia on either tacro or cyclosporine in addition to corticosteroids was shown in this study to lower both total cholesterol (TC) and LDL levels in these patients.¹
   
3. Adult studies have shown that there is longer survival in patients treated with HMG CoA reductase inhibitors.

Summary of Key Evidence

1. Pravastatin therapy in pediatric heart transplant patients resulted in a statistically significant difference in the following: Mean decrease in TC of 32.4 +/- 11.8 (p<0.05), mean decrease in LDL of 31.4 +/- 9.0 (p<0.05).¹
2. The following differences, though not statistically significant, were also observed: mean decrease in Trig of 12.1 +/- 23.5 (p>0.05), mean increase in HDL of 2.5 +/- 3.7 (p>0.05).
3. There was more consistent change (decline in TC and LDL levels) in patients treated with cyclosporine than in those treated with tacrolimus as their primary immunosuppressive agent.
4. No single incident of myositis/rhabdomyolysis occurred in patients on pravastatin in this study.
5. There was no change in frequency of allograft rejection in treated vs. non-treated patients.
   

Additional Comments

• Hyperlipidemia is common after pediatric heart transplant (up to 90% in some studies are greater than 75%ile for age).³
• Total cholesterol is a poor screening tool for other lipid abnormalities (i.e., need full lipid panel).³
• Combined with acute rejection, hypertension, CMV infection, and cytoxic B cell antibody reactions, hyperlipidemia can lead to CAD, reducing long-term graft survival.²
• Most allografts have a half life of approximately 8 years.4
• Hyperlipidemia is believed to be associated with immunosuppression with cyclosporine and steroids. (this is a synergistic effect, not seen with tacrolimus and steroids).^1,4
• Pravastatin has been found to be safe and effective in adult patients at lowering hyperlipidemia.(it is less hydrophilic, therefore less concentrated in muscle cells & not metabolized by liver P450 pathway, so less it is less likely than other statins to interfere with patients’ other drugs).¹
  

Citation

1. Penson MG, Fricker FJ, Thompson JR, Harker K, Williams BJ, Kahler DA, Schowengerdt KO. Safety and efficacy of pravastatin therapy for the prevention of hyperlipidemia in pediatric and adolescent cardiac transplant recipients. Journal of Heart & Lung Transplantation 2001; 20:611-8.
2. Swenson JM, Fricker FJ, Armitage JM. Immunosuppression switch in pediatric heart transplant recipients: cyclosporine to FK 506. Journal of the American College of Cardiology 1995; 25:1183-8.
3. Chin C, Rosenthal D, Bernstein D. Lipoprotein abnormalities are highly prevalent in pediatric heart transplant patients. Pediatric Transplantation 2000; 4:193-9.
4. Taylor DO, Barr ML, Radovancevic B, Renlund DG, Mentzer RM Jr, Smart FW, Tolman DE, Frazier OH, Young JB, VanVeldhuisen P. A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus. Journal of Heart & Lung Transplantation 1999; 18:336-45.
   

CAT Author: Michelle Viglianco-VanPelt, M.D

CAT Appraisers: Robert Schumacher, M.D

Date appraised: October 14, 2002