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Tacrolimus Immunosuppressive Regimens Are Associated with a Mortality Benefit in Lung Transplantation Recipients at a High-Volume Single Center
Abstracts S419
Combined Outcome Death Any Bleeding Event Non-actionable bleed Actionable bleed Fatal bleed Any Thrombotic Event Pump thrombosis Hemolysis CVA/TIA DVT/PE Alive or Transplanted
Warfarin+ASA (n= 44)
Warfarin Alone (n= 32)
p-value
26 (59%) 2 (5%) 19 (43%) 9 (20%) 9 (20%) 1 (2%) 5 (11%) 0 (0%) 1 (2%) 3 (7%) 1 (2%) 42 (95%)
17 (53%) 3 (9%) 11 (34%) 4 (13%) 6 (19%) 1 (3%) 3 (9%) 0 (0%) 1 (3%) 2 (6%) 0 (0%) 29 (91%)
0.645 0.644 0.483 0.539 1.000 1.000 1.000 1.000 1.000 1.000 1.000 0.644
Number (%) or median (IQR)
1( 175) Tacrolimus Immunosuppressive Regimens Are Associated with a Mortality Benefit in Lung Transplantation Recipients at a High-Volume Single Center A.B. Lichvar , M.R. Morrell, J. Hayanga, J.M. Pilewski, M.M. Crespo, J. D’Cunha, A. Zeevi, J.F. McDyer, C.R. Ensor. University of Pittsburgh, Pittsburgh, PA. Purpose: To describe the effectiveness of tacrolimus (FK) immunosuppression regimens (ISRs) in lung transplant recipients (LTRs) on acute cellular rejection (ACR), bronchiolitis obliterans syndrome (BOS), and mortality. Methods: Single-center, retrospective cohort study of adult LTRs treated with FK vs. non-FK containing ISRs. Patients were dichotomized based on FK use at 3 months post-transplant. Primary outcomes were ACR burden (assessed by the novel composite rejection standardization score (CRSS)) and BOS development; secondary outcomes were advanced BOS development and mortality. Normality was assessed and univariate and multivariate parametric and nonparametric statistical tests were used to assess baseline characteristics and outcomes, where appropriate. Freedom from events were compared using Kaplan Meier method with log-rank conversion and risk was assigned using multivariable Cox proportional hazards modeling. Results: 512 (420 FK, 92 non-FK) LTRs were included. Patients were 56% male, 90% Caucasian, and were transplanted mostly for COPD (31%) or ILD (27%). Median patient age was 61.4 years (IQR 51.1 - 67.7). CRSS was significantly lower in patients in FK vs non-FK ISR at 1 year (0.16 vs. 0.25, p= 0.04), but were similar at 3 (0.25 vs. 0.32, p= 0.14), and 5 years (0.25 vs. 0.30, p= 0.07). Death-censored freedom from BOS in FK vs non-FK groups was similar at 3 years (65% vs. 49%, p= 0.33) and better at 5 years in the FK group (42.8% vs. 16%, p< 0.01). Prevalence of advanced BOS was similar in FK vs non-FK groups at 5 years (32% vs. 34%, p= 0.95). Mortality was higher at 3 (39.5% vs. 15.2%, p< 0.001) and at 5 years (60.4% vs. 32.3%, p< 0.001) in the non-FK group. Mortality attributed to rejection was higher in the non-FK group (15.4% vs. 6.6%, p= 0.006). Three-year mortality was independently associated with FK ISRs (HR 0.39, 95%CI 0.25-0.62), MPA use (HR 0.50, 95%CI 0.32-0.78), and single lung transplant (HR 1.7, 95%CI 1.11-2.66). Five-year mortality was independently associated with FK ISRs (HR 0.45, 95% CI 0.33-0.66), MPA use (HR 0.55, 95%CI 0.39-0.77), single lung transplant (HR 1.7, 95%CI 1.23-2.38), and CMV mismatch (HR 1.56, 95%CI 1.15-2.12). Conclusion: FK-based ISRs were associated with a 1-year ACR advantage, 5-year BOS advantage, and both a 3-year and 5-year survival advantage compared to alterative regimens in LTRs. 1( 176) Use of Pentoxifylline to Mitigate Amphotericin Induced Nephrotoxicity K.B. Bain ,1 K.A. Fester,1 C.A. Witt,2 D.E. Byers,2 R.D. Yusen,2 R.R. Hachem.2 1Pharmacy, Barnes Jewish Hospital, St Louis, MO; 2Pulmonary and Critical Care Medicine, Washington University, St Louis, MO.
Purpose: While amphotericin (AMB) remains the drug of choice for many severe invasive fungal infections, its clinical use is limited by nephrotoxicity. Renal dysfunction is of particular concern in lung transplant recipients (LTR) due to the necessity of other nephrotoxic agents, particularly calcineurin inhibitors (CNI). Pentoxifylline (PTX) may prevent AMB-mediated renal artery vasoconstriction by augmenting production of vasodilatory prostaglandins with consequent suppression of vascular congestion. Despite initial literature that PTX reverses AMB mediated acute renal dysfunction in patients receiving cyclosporine, subsequent supporting data are lacking. This study evaluated the role of PTX in mitigating nephrotoxicity associated with lipid formulations of AMB (L-AMB) in LTR on concomitant CNI. Methods: We performed a single center, retrospective cohort study comparing nephrotoxicity (by RIFLE criteria) in LTR who received intravenous L-AMB with or without PTX between 1/2000 and 6/2015. The study excluded LTR on dialysis prior to L-AMB initiation. As per the RIFLE criteria, Risk, Injury or Failure following L-AMB initiation consisted of a 1.5-fold, 2-fold or 3-fold or greater increase in serum creatinine (SCr) and a 25%, 50% or 75% or greater decrease in GFR. LTR could be categorized in multiple RIFLE groups (not mutually exclusive). Statistical analyses were performed using SPSS. Results: Seventeen LTR received L-AMB during the study period. We excluded 3 LTR on dialysis prior to L-AMB, leaving 9 L-AMB alone and 5 L-AMB plus PTX. The groups had similar age, baseline SCr, use of concomitant nephrotoxins, CNI levels and daily L-AMB dosing. PTX use was associated with a decreased incidence of nephrotoxicity reaching the Injury threshold despite receiving a longer duration of L-AMB therapy and higher cumulative doses. Conclusion: In this study of CNI treated LTR, use of PTX in combination with L-AMB was associated with a lower incidence and severity of nephrotoxicity as compared to L-AMB alone. Further study is warranted.
Age, years (range) SCr at time of L-AMB initiation, mg/dL (range) Daily L-AMB dose received, mg/kg (range) Cumulative L-AMB dose received, mg/kg (range) Duration of L-AMB therapy, days (range) Incidence of Risk, n (%) Time to Risk, days (range) Incidence of Injury, n (%) Incidence of Failure, n (%) Incidence of Dialysis, n (%)
L-AMB (N = 9)
L-AMB + PTX (N = 5)
P-value
47 (21–70) 0.9 (0.6-1.5)
53 (28–67) 0.9 (0.6–2.1)
0.797 0.699
4 (1-5)
4 (3 – 5)
0.898
14 (5-105)
54 (30–70)
0.019
4 (2-33)
13 (10–14)
0.019
8 (88%) 2 (1-14) 6 (67%) 3 (33%) 2 (22%)
5 (100%) 10 (1 – 14) 0 0 0
1.0 0.065 0.031 0.258 1.0
1( 177) Medication Regimen Complexity in Older Adults with Heart Failure M.R. Cobretti ,1 K.M. Deininger,1 S.A. Linnebur,2 R.L. Page II,2 J. Lindenfeld,3 C.L. Aquilante.1 1Pharmaceutical Sciences, University of Colorado, Aurora, CO; 2Clinical Pharmacy, University of Colorado, Aurora, CO; 3Vanderbilt Heart and Vascular Institute, Vanderbilt University, Nashville, TN. Purpose: Heart failure (HF) prevalence is increasing in older adults and polypharmacy is a major problem. We quantified medication regimen complexity (MRC) in older adults with HF. We also compared MRC based on age (younger-old vs older-old) and HF etiology [ischemic cardiomyopathy (ISCM) vs non-ischemic cardiomyopathy (NISCM)]. Methods: Medication lists were abstracted from the medical records of HF patients aged 60 to 89 years. Medications were categorized into 3 types: disease prescription (HF Rx), other prescription (Other Rx), and OTC. Medications were counted and dosage forms, frequencies, and additional directions were scored using the validated Patient-level Medication Regimen Complexity (pMRCI) tool. Total pMRCI scores were calculated, along with sub-scores for each med type. Data were compared between groups using GLM analysis, with NYHA class and sex as covariates.
Combined Outcome Death Any Bleeding Event Non-actionable bleed Actionable bleed Fatal bleed Any Thrombotic Event Pump thrombosis Hemolysis CVA/TIA DVT/PE Alive or Transplanted
Warfarin+ASA (n= 44)
Warfarin Alone (n= 32)
p-value
26 (59%) 2 (5%) 19 (43%) 9 (20%) 9 (20%) 1 (2%) 5 (11%) 0 (0%) 1 (2%) 3 (7%) 1 (2%) 42 (95%)
17 (53%) 3 (9%) 11 (34%) 4 (13%) 6 (19%) 1 (3%) 3 (9%) 0 (0%) 1 (3%) 2 (6%) 0 (0%) 29 (91%)
0.645 0.644 0.483 0.539 1.000 1.000 1.000 1.000 1.000 1.000 1.000 0.644
Number (%) or median (IQR)
1( 175) Tacrolimus Immunosuppressive Regimens Are Associated with a Mortality Benefit in Lung Transplantation Recipients at a High-Volume Single Center A.B. Lichvar , M.R. Morrell, J. Hayanga, J.M. Pilewski, M.M. Crespo, J. D’Cunha, A. Zeevi, J.F. McDyer, C.R. Ensor. University of Pittsburgh, Pittsburgh, PA. Purpose: To describe the effectiveness of tacrolimus (FK) immunosuppression regimens (ISRs) in lung transplant recipients (LTRs) on acute cellular rejection (ACR), bronchiolitis obliterans syndrome (BOS), and mortality. Methods: Single-center, retrospective cohort study of adult LTRs treated with FK vs. non-FK containing ISRs. Patients were dichotomized based on FK use at 3 months post-transplant. Primary outcomes were ACR burden (assessed by the novel composite rejection standardization score (CRSS)) and BOS development; secondary outcomes were advanced BOS development and mortality. Normality was assessed and univariate and multivariate parametric and nonparametric statistical tests were used to assess baseline characteristics and outcomes, where appropriate. Freedom from events were compared using Kaplan Meier method with log-rank conversion and risk was assigned using multivariable Cox proportional hazards modeling. Results: 512 (420 FK, 92 non-FK) LTRs were included. Patients were 56% male, 90% Caucasian, and were transplanted mostly for COPD (31%) or ILD (27%). Median patient age was 61.4 years (IQR 51.1 - 67.7). CRSS was significantly lower in patients in FK vs non-FK ISR at 1 year (0.16 vs. 0.25, p= 0.04), but were similar at 3 (0.25 vs. 0.32, p= 0.14), and 5 years (0.25 vs. 0.30, p= 0.07). Death-censored freedom from BOS in FK vs non-FK groups was similar at 3 years (65% vs. 49%, p= 0.33) and better at 5 years in the FK group (42.8% vs. 16%, p< 0.01). Prevalence of advanced BOS was similar in FK vs non-FK groups at 5 years (32% vs. 34%, p= 0.95). Mortality was higher at 3 (39.5% vs. 15.2%, p< 0.001) and at 5 years (60.4% vs. 32.3%, p< 0.001) in the non-FK group. Mortality attributed to rejection was higher in the non-FK group (15.4% vs. 6.6%, p= 0.006). Three-year mortality was independently associated with FK ISRs (HR 0.39, 95%CI 0.25-0.62), MPA use (HR 0.50, 95%CI 0.32-0.78), and single lung transplant (HR 1.7, 95%CI 1.11-2.66). Five-year mortality was independently associated with FK ISRs (HR 0.45, 95% CI 0.33-0.66), MPA use (HR 0.55, 95%CI 0.39-0.77), single lung transplant (HR 1.7, 95%CI 1.23-2.38), and CMV mismatch (HR 1.56, 95%CI 1.15-2.12). Conclusion: FK-based ISRs were associated with a 1-year ACR advantage, 5-year BOS advantage, and both a 3-year and 5-year survival advantage compared to alterative regimens in LTRs. 1( 176) Use of Pentoxifylline to Mitigate Amphotericin Induced Nephrotoxicity K.B. Bain ,1 K.A. Fester,1 C.A. Witt,2 D.E. Byers,2 R.D. Yusen,2 R.R. Hachem.2 1Pharmacy, Barnes Jewish Hospital, St Louis, MO; 2Pulmonary and Critical Care Medicine, Washington University, St Louis, MO.
Purpose: While amphotericin (AMB) remains the drug of choice for many severe invasive fungal infections, its clinical use is limited by nephrotoxicity. Renal dysfunction is of particular concern in lung transplant recipients (LTR) due to the necessity of other nephrotoxic agents, particularly calcineurin inhibitors (CNI). Pentoxifylline (PTX) may prevent AMB-mediated renal artery vasoconstriction by augmenting production of vasodilatory prostaglandins with consequent suppression of vascular congestion. Despite initial literature that PTX reverses AMB mediated acute renal dysfunction in patients receiving cyclosporine, subsequent supporting data are lacking. This study evaluated the role of PTX in mitigating nephrotoxicity associated with lipid formulations of AMB (L-AMB) in LTR on concomitant CNI. Methods: We performed a single center, retrospective cohort study comparing nephrotoxicity (by RIFLE criteria) in LTR who received intravenous L-AMB with or without PTX between 1/2000 and 6/2015. The study excluded LTR on dialysis prior to L-AMB initiation. As per the RIFLE criteria, Risk, Injury or Failure following L-AMB initiation consisted of a 1.5-fold, 2-fold or 3-fold or greater increase in serum creatinine (SCr) and a 25%, 50% or 75% or greater decrease in GFR. LTR could be categorized in multiple RIFLE groups (not mutually exclusive). Statistical analyses were performed using SPSS. Results: Seventeen LTR received L-AMB during the study period. We excluded 3 LTR on dialysis prior to L-AMB, leaving 9 L-AMB alone and 5 L-AMB plus PTX. The groups had similar age, baseline SCr, use of concomitant nephrotoxins, CNI levels and daily L-AMB dosing. PTX use was associated with a decreased incidence of nephrotoxicity reaching the Injury threshold despite receiving a longer duration of L-AMB therapy and higher cumulative doses. Conclusion: In this study of CNI treated LTR, use of PTX in combination with L-AMB was associated with a lower incidence and severity of nephrotoxicity as compared to L-AMB alone. Further study is warranted.
Age, years (range) SCr at time of L-AMB initiation, mg/dL (range) Daily L-AMB dose received, mg/kg (range) Cumulative L-AMB dose received, mg/kg (range) Duration of L-AMB therapy, days (range) Incidence of Risk, n (%) Time to Risk, days (range) Incidence of Injury, n (%) Incidence of Failure, n (%) Incidence of Dialysis, n (%)
L-AMB (N = 9)
L-AMB + PTX (N = 5)
P-value
47 (21–70) 0.9 (0.6-1.5)
53 (28–67) 0.9 (0.6–2.1)
0.797 0.699
4 (1-5)
4 (3 – 5)
0.898
14 (5-105)
54 (30–70)
0.019
4 (2-33)
13 (10–14)
0.019
8 (88%) 2 (1-14) 6 (67%) 3 (33%) 2 (22%)
5 (100%) 10 (1 – 14) 0 0 0
1.0 0.065 0.031 0.258 1.0
1( 177) Medication Regimen Complexity in Older Adults with Heart Failure M.R. Cobretti ,1 K.M. Deininger,1 S.A. Linnebur,2 R.L. Page II,2 J. Lindenfeld,3 C.L. Aquilante.1 1Pharmaceutical Sciences, University of Colorado, Aurora, CO; 2Clinical Pharmacy, University of Colorado, Aurora, CO; 3Vanderbilt Heart and Vascular Institute, Vanderbilt University, Nashville, TN. Purpose: Heart failure (HF) prevalence is increasing in older adults and polypharmacy is a major problem. We quantified medication regimen complexity (MRC) in older adults with HF. We also compared MRC based on age (younger-old vs older-old) and HF etiology [ischemic cardiomyopathy (ISCM) vs non-ischemic cardiomyopathy (NISCM)]. Methods: Medication lists were abstracted from the medical records of HF patients aged 60 to 89 years. Medications were categorized into 3 types: disease prescription (HF Rx), other prescription (Other Rx), and OTC. Medications were counted and dosage forms, frequencies, and additional directions were scored using the validated Patient-level Medication Regimen Complexity (pMRCI) tool. Total pMRCI scores were calculated, along with sub-scores for each med type. Data were compared between groups using GLM analysis, with NYHA class and sex as covariates.