The efficacy and tolerability of ezetimibe in cardiac transplant recipients taking cyclosporin.
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.


CONCLUSIONS
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.
Shaw
Steven M
SM
North West Regional Heart Centre, University of South Manchester NHS Foundation Trust, Manchester, United Kingdom. doctorshaw@doctors.org.uk
Chaggar
Parminder
P
Ritchie
James
J
Shah
Mohammed K H
MK
Baynes
Anna C
AC
O'Neill
Nicola
N
Fildes
James E
JE
Yonan
Nizar
N
Williams
Simon G
SG
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D004311:Double-Blind Method; D000069438:Ezetimibe; D005260:Female; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012449:Safety
D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D008077:Lipoproteins, LDL; D010919:Placebos; D016572:Cyclosporine; D002784:Cholesterol; D000069438:Ezetimibe