Low-dose lovastatin safely lowers cholesterol after cardiac transplantation.

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.

Heart transplantation may not improve quality of life for patients with stable heart failure.

Heart transplantation is a therapeutic option for many patients with end-stage heart failure. Vigorous medical therapy has evolved so that many patients eligible for heart transplantation can now be discharged and stabilized with medical therapy. Heart transplantation improves survival, but it has not been compared previously with sustained medical therapy with regard to quality of life. We compared quality of life for 24 patients who survived at least 6 months after heart transplantation with that for 20 patients clinically similar at baseline who survived at least 6 months with sustained medical therapy. Quality of life was assessed by using three questionnaires. Both groups were similar in psychosocial functioning, with patients receiving medical therapy reporting greater dysfunction in social activities, as compared with those who underwent heart transplantation. No differences were seen in 6-minute walking distances and employment status. Survival benefits are expected with heart transplantation; however, quality of life for survivors may not be different than that for patients who survive with sustained medical therapy.

Randomized study of high dose oral cyclosporine therapy for mild acute cardiac rejection.

Mild acute rejection progresses to moderate rejection in approximately one third of the cases. Standard rejection therapy would then be instituted with the attendant risk of infection and other side effects. We randomized 40 episodes of mild acute rejection (20 episodes in each group) to receive no additional therapy or to have the oral cyclosporine dose increased for 7 to 10 days with repeat endomyocardial biopsy performed. In the group with no additional therapy 30% progressed to moderate rejection, whereas in the group with increased doses of oral cyclosporine, 10% progressed to moderate rejection (p = 0.10). As the purpose of our study was to assess the efficacy of increased cyclosporine levels for preventing progression from mild to moderate rejection, the treated group was redefined according to whether the cyclosporine level increased by greater than or equal to 50% during the study. In this treated group average cyclosporine levels increased from 169 +/- 78 to 413 +/- 267 ng/ml. Progression to moderate rejection occurred in one of 21 cases (5%) compared with seven of 19 cases (37%) in the group without an increase in cyclosporine level (p less than 0.05). The transient increase in cyclosporine levels was well tolerated. This study demonstrates that the use of high dose oral cyclosporine to treat mild acute rejection is well tolerated and may reduce progression to moderate rejection when a significant increase in cyclosporine level is achieved.