Session Name: Non-Organ Specific: Pharmacogenomics / Pharmacokinetics
Session Date & Time: None. Available on demand.
*Purpose: The aim of the study was to characterize the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in solid organ transplant recipients (SOTR).
*Methods: This retrospective study included SOTR age ≥18 yrs who used a PCSK9 inhibitor for at least 4-wks post-transplant with at least 1 lipid panel available. Heart, lung, kidney, and liver transplant recipients who were transplanted between Jul 1,1990-2020 were included. Data collection ended on Oct 31, 2020, and included SOTR demographics, atherosclerotic cardiovascular disease (ASCVD) history, rejection, graft loss, and death in the 6 months following PCSK9 initiation. The primary efficacy outcome was change in LDL and total cholesterol (TC) from baseline to 6 months. The primary safety outcome was incidence of presumed or proven rejection. Secondary endpoints included change in calcineurin inhibitor (CNI) or mammalian target of rapamycin (mTOR) troughs or doses and incidence of ASCVD in the 6 months after PCSK9 initiation.
*Results: Nineteen SOTRs were included. Mean age was 56 yrs (±11.8) and SOTRs were primarily males (63.2%) and white (84.2%). 52.6% of SOTRs were followed for 6 months. Transplanted organs included kidney (42.1%), heart (31.6%), liver (21.1%), and lung (5.3%). Median time from transplant to PCSK9 initiation was 4.6 yrs (IQR 0.84-16.4). Twelve were initiated on evolocumab and 7 on alirocumab. Over half (52.6%) were on concomitant statin therapy. Significant reductions in TC and LDL were observed upon initiation of PCSK9 therapy (Table 1). Immunosuppression regimens consisted of tacrolimus (89.5%), cyclosporine (5.3%), and sirolimus (5.3%). No significant changes in CNI or mTOR troughs or dosing were observed. New ASCVD events occurred in 15.7% of SOTRs. All had a prior history of ASCVD, 2 had an myocardial infarction and a 3rd required stent placement for occluded coronaries. No episodes of rejection, graft loss, or death occurred during the study period.
*Conclusions: PCSK9 inhibitor use in SOTR appears to be efficacious and safe. No episodes of rejection or changes in immunosuppression dosing or CNI or mTOR troughs were observed during the study. Further research on the longitudinal effects of PCSK9 therapy in SOTR is warranted.
|Parameter Evaluated||Baseline (Mean ± SD)||6 months (Mean ± SD)||Mean Change (Mean ± SD)||p-value|
|LDL (mg/dL)||106.9 ± 55.6||39.8 ± 19.7||80 ± 50.2||0.033|
|Total Cholesterol (mg/dL)||195.3 ± 64.4||128.2 ± 34.0||76.2 ± 67.1||0.012|
|Tacrolimus trough (mcg/L)||7.1 ± 1.9||9.5 ± 5.0||2.0 ± 4.0||0.126|
|Tacrolimus dose (mg/day)||5.3 ± 4.1||5.2 ± 4.0||0.0 ± 1.7||1.000|
To cite this abstract in AMA style:Ucci A, Norris M, Trofe-Clark J, Fallah T, Meck M, Samudralwar R, Genuardi MV. Evaluation of Safety and Efficacy of PCSK9 Inhibitors in Solid Organ Transplant Recipients: Experience at a Large Multi-organ Transplant Center [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/evaluation-of-safety-and-efficacy-of-pcsk9-inhibitors-in-solid-organ-transplant-recipients-experience-at-a-large-multi-organ-transplant-center/. Accessed July 24, 2021.
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