Cardiovascular Parameters to 2 years After Kidney Transplantation Following Early Switch to Everolimus Without Calcineurin Inhibitor Therapy: An Analysis of the Randomized ELEVATE Study.
Mammalian target of rapamycin inhibitors may confer cardioprotective advantages, but clinical data are limited.



In the open-label ELEVATE trial, kidney transplant patients were randomized at 10 to 14 weeks after transplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified end points included left ventricular mass index and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity.



The mean change in left ventricular mass index from randomization was similar with everolimus versus CNI (month 24, -4.37 g/m versus -5.26 g/m; mean difference, 0.89 [p = 0.392]). At month 24, left ventricular hypertrophy was present in 41.7% versus 37.7% of everolimus and CNI patients, respectively. Mean pulse wave velocity remained stable with both everolimus (mean change from randomization to month 12, -0.24 m/s; month 24, -0.03 m/s) and CNI (month 12, 0.11 m/s; month 24, 0.16 m/s). The change in mean ambulatory nighttime blood pressure from randomization showed a benefit for diastolic pressure at month 12 (P = 0.039) but not at month 24. Major adverse cardiac events occurred in 1.1% and 4.2% of everolimus-treated and CNI-treated patients, respectively, by month 12 (P = 0.018) and 2.3% (8/353) and 4.5% by month 24 (P = 0.145).



Overall, these data do not suggest a clinically relevant effect on cardiac end points after early conversion from CNI to a CNI-free everolimus-based regimen.
1 Section of Nephrology, Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 2 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. 3 Department of Nephrology, University Hospital of Bellvitge, Feixa Llarga s/n, L'Hospitalet de Llobregat, Barcelona, Spain. 4 Renal Service and Transplant Program, Hospital Privado Centro Medico de Cordoba, Cordoba, Argentina. 5 Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6 Department of Nephrology, Monash Health and Centre for Inflammatory Diseases, Department of Medicine, Monash University, Melbourne, Australia. 7 Department of Infectious Diseases and Department of Nephrology, University Duisburg-Essen, Essen, North Rhine-Westphalia, Germany. 8 Renal Transplant Unit, Department of Nephrology, Miguel Servet University Hospital, Isabel la Católica s/n, Zaragoza, Spain. 9 Department of Nephrology, Istanbul School of Medicine, Istanbul, Turkey. 10 Biometrics and Statistical Science, Novartis Pharmaceuticals, East Hanover, NJ. 11 Research and Development, Novartis Pharma AG, Basel, Switzerland. 12 Department of Nephrology, Campus Benjamin Franklin, Charite´ - Universitätsmedizin, Berlin, Germany. 13 Department of Cardiology, Oslo University Hospital, Rikshospitalet, Nydalen, Oslo, Norway.
Hallvard
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Holdaas
Johan W
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de Fijter
Josep M
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Pablo
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Massari
Björn
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Nashan
John
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Kanellis
Oliver
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Witzke
Alex
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Gutierrez-Dalmau
Aydin
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Turkmen
Zailong
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Wang
Patricia
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Lopez
Peter
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Bernhardt
Jossy
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D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D057915:Drug Substitution / Q000379:methods; D004452:Echocardiography; D000068338:Everolimus / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000150:complications / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus