Cardiovascular (CV) death is a leading cause of death in kidney transplant recipients (KTR). Increased aortic arterial stiffness is strongly associated with the development of CV disease and is an independent predictor of mortality. Pulse Wave Velocity (PWV), a direct measure of arterial stiffness, is a highly reliable prognostic parameter for CV morbidity and mortality. In a randomized, open-label, multi-center, two sequence, three period cross-over study to compare the steady state pharmacokinetics of once-daily extended release MeltDose® tacrolimus tablets (Envarsus XR) to immediate release twice-daily tacrolimus capsules (IR-Tac) in stable African American renal transplant patients (6 months or greater post-transplant), at one center PWV assessments were conducted at randomization and at the month 6 visit for Envarsus XR (n=9) and IR-Tac (n=12) KTR. From baseline (10.10±3.7 meter/second[m/s]) to 6 months (10.95±3.9 m/s), mean PWV for IR-Tac increased by 1.04m/s while mean PWV decreased by 1.19m/s among Envarsus XR KTR (baseline: 8.66±2.2; 6 mos.: 8.23±0.98). Decrease in central augmentation pressure was also favorable for KTR on Envarsus XR, with a 2mmHg decrease (13.2±8.2 mmHg to 11.3±5.9 mmHg) from baseline to 6 mos., while IR-Tac was associated with an increase (7.6±5.8mmHg to 9.8±7.8 mmHg). The mean change in heart rate was the same between groups (70.22 to 67.42 beats/minute for IR-Tac vs 66.95 to 62.66 beats/minute for Envarsus XR). After correcting for heart rate of 75 beats/minute, the difference in central augmentation index between baseline and 6 months for Envarsus XR was a mean of 4.99%, p=0.066, while an increase of a mean of 7.91% was seen for IR-Tac. These independent CV tests suggest favorable direction for Envarsus XR in ability to potentially improve CV status. Future study in a larger sample is warranted as PWV is a surrogate endpoint for patients such as African American KTR with higher CV risk.

CITATION INFORMATION: Trofe-Clark J, Townsend R, Neubauer R, Lim M, Callahan L, Bloom R. Pulse Wave Velocity Amongst African-American Kidney Transplant Recipients Randomized to Once-Daily MeltDose Tacrolimus Tablets (Envarsus XR) vs. Traditional Twice-Daily Tacrolimus Capsules: Exploratory Results from a Phase III Trial. Am J Transplant. 2016;16 (suppl 3).

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