BACKGROUND: Despite statin treatment, hyperlipidemia remains problematic after cardiac transplantation and is associated with the development of cardiac allograft vasculopathy. The cholesterol absorption inhibitor ezetimibe may offer a viable option for add on therapy; however, questions have been raised regarding the safety of this during concomitant cyclosporin treatment. METHODS: This is the first placebo controlled, randomized double blinded trial assessing the efficacy and tolerability of ezetimibe in cardiac transplant recipients receivingcyclosporin. Sixty-eight cardiac transplant patients were randomized to receive ezetimibe (10 mg) or matching placebo for 6 months in addition to usual treatments. Fasting blood tests were performed at regular time intervals during the study. RESULTS:Fifty-nine patients completed the study. At 6 months, ezetimibe had reduced total cholesterol by 18% (5.4+/-1.1 to 4.4+/-0.7 mmol/L, P<0.001), low-density lipoprotein cholesterol by 26% (3.0+/-1.0 to 2.1+/-0.7 mmol/L, P<0.001), and triglycerides by 13.5% (2.3+/-1.3 to 1.8+/-0.9 mmol/L, P=0.02). Tolerability was excellent with no patients experiencing predefined safety endpoints. An equal number of patients withdrew consent from each arm of the study because of perceived side effects. Specific analysis confirmed ezetimibe had no significant effect on cyclosporin levels. CONCLUSION: We conclude that ezetimibe is both efficacious and tolerable in cardiac transplant recipients takingcyclosporin. It can be safely considered as add on therapy in patients taking statins (or as monotherapy) to further reduce low-density lipoprotein levels, which may in turn reduce the risk of cardiac allograft vasculopathy.
RCT Entities:
BACKGROUND: Despite statin treatment, hyperlipidemia remains problematic after cardiac transplantation and is associated with the development of cardiac allograft vasculopathy. The cholesterol absorption inhibitor ezetimibe may offer a viable option for add on therapy; however, questions have been raised regarding the safety of this during concomitant cyclosporin treatment. METHODS: This is the first placebo controlled, randomized double blinded trial assessing the efficacy and tolerability of ezetimibe in cardiac transplant recipients receiving cyclosporin. Sixty-eight cardiac transplant patients were randomized to receive ezetimibe (10 mg) or matching placebo for 6 months in addition to usual treatments. Fasting blood tests were performed at regular time intervals during the study. RESULTS: Fifty-nine patients completed the study. At 6 months, ezetimibe had reduced total cholesterol by 18% (5.4+/-1.1 to 4.4+/-0.7 mmol/L, P<0.001), low-density lipoprotein cholesterol by 26% (3.0+/-1.0 to 2.1+/-0.7 mmol/L, P<0.001), and triglycerides by 13.5% (2.3+/-1.3 to 1.8+/-0.9 mmol/L, P=0.02). Tolerability was excellent with no patients experiencing predefined safety endpoints. An equal number of patients withdrew consent from each arm of the study because of perceived side effects. Specific analysis confirmed ezetimibe had no significant effect on cyclosporin levels. CONCLUSION: We conclude that ezetimibe is both efficacious and tolerable in cardiac transplant recipients taking cyclosporin. It can be safely considered as add on therapy in patients taking statins (or as monotherapy) to further reduce low-density lipoprotein levels, which may in turn reduce the risk of cardiac allograft vasculopathy.