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. 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.

Liquid chromatography-mass spectrometry measurement of tacrolimus in finger-prick samples compared with venous whole blood samples.

BACKGROUND: Finger-prick sampling is an alternative strategy for monitoring immunosuppressive drug concentrations that could be useful in reducing outpatient visits. We investigated the correlation between venous and finger-prick samples in a group of adult thoracic transplant patients. METHODS: Blood samples (n = 65) for the measurement of whole blood tacrolimus were collected from adult heart (n = 18) and lung transplant (n = 20) recipients receiving tacrolimus-based immunosuppressive therapy and a finger-prick sample was taken at the same time. RESULTS: Between-batch assay imprecision (coefficient of variation [CV], %) for the last 12 months (n = 270) at concentrations of 3.5, 6.9 and 13.9 microg/L was 8.0%, 5.4% and 5.2%, respectively. Passing and Bablok regression analysis between finger-prick and venous blood showed finger-prick tacrolimus = 1.02 (venous blood tacrolimus) -0.06. Bland-Altman analysis showed good agreement with a bias of 0.114 microg/L and 95% limits of agreement from -1.0 to 1.2 microg/L. CONCLUSIONS: The liquid chromatography mass spectrometry methodology that we have developed has the potential to allow patients or their carers to collect finger-prick blood samples at home and send them to the laboratory using the routine mail service. We believe that finger-prick blood sampling has an important role to play in the care of transplant patients receiving immunosuppressive drugs, including tacrolimus.

Monitoring of cyclosporine levels in transplant recipients using self-administered fingerprick sampling.

Use of C(2) monitoring for cyclosporine A (CsA) microemulsion results in improved clinical outcomes vs. trough (C(0)) monitoring. Logistical issues include accurate timing of the C(2) sample; requirement for sample dilution with most standard assay techniques; and inconvenience for patients. Recently, it has been shown that CsA concentrations in capillary blood correlate closely with levels in venepuncture samples, and that liquid chromatography tandem mass spectrometry (LC-MS/MS) can analyse CsA concentration using undiluted capillary blood from fingerprick samples. In a study to assess the feasibility of CsA monitoring, 52 stable heart transplant patients were provided with kits to take fingerprick trough and C(2) blood samples at home, returning them to the laboratory by post for LC-MS/MS analysis. In total, 225 samples were provided, of which 14 (6%) were unsuitable for analysis because of clotting (n = 10) or insufficient volume (n = 4). Discomfort was not a problem and initial difficulties that some patients reported in taking the samples resolved with experience. All samples were returned by the postal system in a timely manner. Use of fingerprick assays could allow transplant physicians to have access to C(2) levels when patients visit the clinic for review, and avoids the need for patients to attend the clinic or local healthcare centre solely for venepuncture. A barrier to more widespread introduction of fingerprick testing is likely to be lack of suitable MS facilities and trained personnel. In conclusion, self-administered fingerprick testing for CsA blood levels is practical to implement and highly convenient for patients and offers advantages for the transplant team.