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Low-dose lovastatin safely lowers cholesterol after cardiac transplantation
J A Kobashigawa1, F L Murphy, L W Stevenson
1Division of Cardiology, UCLA School of Medicine 90024-1679.
Insights
Low-dose lovastatin effectively manages hypercholesterolemia in cardiac transplant recipients. This cholesterol-lowering drug is generally safe, though altered drug metabolism necessitates careful monitoring in these patients.
Area of Science:
- Cardiology
- Pharmacology
- Transplantation Medicine
Background:
- Hypercholesterolemia is common in cardiac transplant patients, worsening graft coronary arteriopathy and peripheral vascular disease.
- Standard lovastatin doses (40-80 mg/day) are effective for cholesterol reduction but pose a risk of rhabdomyolysis in transplant recipients.
Purpose of the Study:
- To evaluate the efficacy and safety of low-dose lovastatin (10-20 mg/day) for managing hypercholesterolemia in cardiac transplant patients.
- To investigate potential alterations in lovastatin metabolism in this patient population.
Main Methods:
- A study involving 44 cardiac transplant recipients with cholesterol >200 mg/dl, who received daily lovastatin doses of 10-20 mg.
- Measurement of lovastatin enzyme inhibitor levels in six patients to assess drug metabolism.
- Monitoring of cholesterol levels, low-density lipoprotein (LDL) fractions, and creatine phosphokinase (CPK) levels.
Main Results:
- Lovastatin significantly reduced total cholesterol by 28% (282 to 208 mg/dl, p<0.005), primarily by lowering LDL cholesterol.
- The low-dose regimen was well-tolerated in 43 out of 44 patients, with no symptoms or abnormal CPK levels.
- One patient experienced rhabdomyolysis and reversible renal failure upon increasing the dose to 40 mg daily.
- Lovastatin enzyme inhibitor levels were 4.2-7.8 times higher in transplant patients compared to healthy volunteers, suggesting altered metabolism, possibly due to cyclosporine.
Conclusions:
- Low-dose lovastatin (10-20 mg/day) is effective in lowering cholesterol in cardiac transplant recipients.
- Altered drug metabolism, potentially influenced by concomitant medications like cyclosporine, is evident in these patients.
- Careful monitoring of lovastatin levels and enzyme inhibitor levels may be necessary for safe and effective treatment in cardiac transplant recipients.
Abstract:
Hypercholesterolemia occurs in many cardiac transplant patients and may aggravate graft coronary arteriopathy as well as contributing to peripheral vascular disease. Lovastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase, in doses of 40-80 mg/day effectively lowers cholesterol in the general cardiac population but has been associated with rhabdomyolysis in cardiac transplant recipients. To determine whether lower doses of lovastatin would be effective and safe for lowering cholesterol after cardiac transplantation, 44 patients with blood cholesterol greater than 200 mg/dl at least 6 months after cardiac transplantation received 10-20 mg lovastatin daily. In addition, lovastatin enzyme inhibitor level was assayed in six patients to determine whether metabolism of the drug was abnormal. Lovastatin decreased total cholesterol by 28% from 282 +/- 54 to 208 +/- 62 mg/dl (p less than 0.005), primarily because of reduction in the low-density lipoprotein fractions, and was well-tolerated without any symptoms or abnormal creatine phosphokinase levels in 43 of 44 patients. One patient developed rhabdomyolysis and reversible renal failure when lovastatin was increased to 40 mg daily. Enzyme inhibitor levels in the six transplant patients were 4.2-7.8 times higher than those measured in normal volunteers. Low-dose lovastatin effectively lowers cholesterol in patients after transplantation, but metabolism is altered, perhaps by cyclosporine. Monitoring of enzyme inhibitor levels may be required to allow safe administration of this drug to cardiac transplant recipients.