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Effects of INR Variability and Time in the Therapeutic Range on the Rates of Gastrointestinal Bleeding in Patients Supported by Left Ventricular Assist Devices
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The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
3 Pulmonary & Critical Care, Washington University, Saint Louis, MO; and the 4Surgery, Washington University, Saint Louis, MO . Purpose: CARV infections are associated with an increased risk of CLAD development and progression. Inhaled corticosteroids are used to treat airway inflammation, but there is a dearth of data regarding their use in lung transplantation. This study aimed to examine the effect of inhaled beclomethasone on the development and progression of CLAD after CARV. Methods: Single-center, double blind, pilot, randomized, placebo controlled trial of inhaled beclomethasone in adult LTR diagnosed with a CARV between Jan 2017 and Dec 2017. Patients were randomized in a 1:1 ratio stratified by BOS stage (BOS 0/0p vs 1/2) within 7 days of CARV. Study drug was continued for 6 months. The primary endpoint was freedom from new or progressive CLAD (defined as a 15% decline in pre CARV FEV1). Secondary endpoints included all-cause mortality and development of new DSA post-CARV. Results: 7 patients were randomized to inhaled beclomethasone and 8 to placebo. Baseline demographics were well matched between groups including gender, age at LTR, time from LTR to CARV, upper vs lower CARV, BOS stage, and DSA at the time of study enrollment (Table 1). There was no difference in freedom from CLAD or CLAD progression between the 2 groups (Figure 1). No patients died or developed new DSA during the study period. Conclusion: Inhaled beclomethasone was not associated with a lower incidence of new or progressive CLAD after CARV when compared to placebo. However, this study had limited power and sample size. Additional studies are necessary to assess the potential benefit of inhaled corticosteroids in LTR after CARV.
475 Effects of INR Variability and Time in the Therapeutic Range on the Rates of Gastrointestinal Bleeding in Patients Supported by Left Ventricular Assist Devices A. Mardis,1 M. Freiter,2 B. Mierzejewski,2 and M. Adams.3 1Department of Pharmacy, Palmetto Health, Columbia, SC; 2College of Pharmacy, University of South Carolina, Columbia, SC; and the 3Department of Family and Preventive Medicine, University of South Carolina College of Medicine, Columbia, SC. Purpose: Patients supported with left ventricular assist devices (LVADs) require chronic anticoagulation with warfarin to prevent thrombus formation within the device. While a goal INR range of 2 to 3 is generally accepted as appropriate, higher time in the therapeutic range (TTR) has been associated with improved outcomes. This analysis aimed to also determine the impact of INR variability on gastrointestinal bleeding (GIB) events. Methods: This was a retrospective, longitudinal cohort study at a single center from January 2015 to December 2017. Standard INR goal was 2 to 3 but could be adjusted on a patient-specific basis. GIB was defined per the standard INTERMACS definition. INR TTR was calculated using the Rosendaal method, and coefficient of variation (CV) was calculated as a ratio of standard deviation to the mean. For the primary analysis, patients who experienced a GIB were compared to those who had not. Results: Baseline characteristics were similar between the two groups (Table 1). Of the 87 subjects analyzed in the study, 23 (26.4%) experienced a GIB (average time to bleed 363 days) with 9 patients developing a second GIB. The overall TTR for the population was 65.0%, and the overall CV was 27.3%. Patients who had a GIB had a lower mean TTR than those who did not bleed (58.8% vs 67.2%, p=0.03). For those that bled, the TTR in the 30 days prior to the GIB event (50.4%) was lower than the overall TTR (p=0.032). Patients who experienced a GIB also had significantly more variability in their INR values than those who did not bleed (31.2% vs 25.8%, p=0.035) (Table 2). Conclusion: Both increased INR variability and decreased TTR are associated with increased rates of GIB in patients supported by LVADs. This is the first study to explore whether more INR variation puts patients with LVADs at greater risk of developing a GIB. Further prospective studies are warranted to further test this hypothesis.
476 Appropriate Management of Drug Interactions Results in Safe Use of Hepatitis C Therapies in Heart Transplant Recipients K. Boyle, R.E. Fowler, A. Pollack, C. Edmonds, J. Gray, J. Lindenfeld and K. Schlendorf. Vanderbilt University Medical Center, Nashville, TN.
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
3 Pulmonary & Critical Care, Washington University, Saint Louis, MO; and the 4Surgery, Washington University, Saint Louis, MO . Purpose: CARV infections are associated with an increased risk of CLAD development and progression. Inhaled corticosteroids are used to treat airway inflammation, but there is a dearth of data regarding their use in lung transplantation. This study aimed to examine the effect of inhaled beclomethasone on the development and progression of CLAD after CARV. Methods: Single-center, double blind, pilot, randomized, placebo controlled trial of inhaled beclomethasone in adult LTR diagnosed with a CARV between Jan 2017 and Dec 2017. Patients were randomized in a 1:1 ratio stratified by BOS stage (BOS 0/0p vs 1/2) within 7 days of CARV. Study drug was continued for 6 months. The primary endpoint was freedom from new or progressive CLAD (defined as a 15% decline in pre CARV FEV1). Secondary endpoints included all-cause mortality and development of new DSA post-CARV. Results: 7 patients were randomized to inhaled beclomethasone and 8 to placebo. Baseline demographics were well matched between groups including gender, age at LTR, time from LTR to CARV, upper vs lower CARV, BOS stage, and DSA at the time of study enrollment (Table 1). There was no difference in freedom from CLAD or CLAD progression between the 2 groups (Figure 1). No patients died or developed new DSA during the study period. Conclusion: Inhaled beclomethasone was not associated with a lower incidence of new or progressive CLAD after CARV when compared to placebo. However, this study had limited power and sample size. Additional studies are necessary to assess the potential benefit of inhaled corticosteroids in LTR after CARV.
475 Effects of INR Variability and Time in the Therapeutic Range on the Rates of Gastrointestinal Bleeding in Patients Supported by Left Ventricular Assist Devices A. Mardis,1 M. Freiter,2 B. Mierzejewski,2 and M. Adams.3 1Department of Pharmacy, Palmetto Health, Columbia, SC; 2College of Pharmacy, University of South Carolina, Columbia, SC; and the 3Department of Family and Preventive Medicine, University of South Carolina College of Medicine, Columbia, SC. Purpose: Patients supported with left ventricular assist devices (LVADs) require chronic anticoagulation with warfarin to prevent thrombus formation within the device. While a goal INR range of 2 to 3 is generally accepted as appropriate, higher time in the therapeutic range (TTR) has been associated with improved outcomes. This analysis aimed to also determine the impact of INR variability on gastrointestinal bleeding (GIB) events. Methods: This was a retrospective, longitudinal cohort study at a single center from January 2015 to December 2017. Standard INR goal was 2 to 3 but could be adjusted on a patient-specific basis. GIB was defined per the standard INTERMACS definition. INR TTR was calculated using the Rosendaal method, and coefficient of variation (CV) was calculated as a ratio of standard deviation to the mean. For the primary analysis, patients who experienced a GIB were compared to those who had not. Results: Baseline characteristics were similar between the two groups (Table 1). Of the 87 subjects analyzed in the study, 23 (26.4%) experienced a GIB (average time to bleed 363 days) with 9 patients developing a second GIB. The overall TTR for the population was 65.0%, and the overall CV was 27.3%. Patients who had a GIB had a lower mean TTR than those who did not bleed (58.8% vs 67.2%, p=0.03). For those that bled, the TTR in the 30 days prior to the GIB event (50.4%) was lower than the overall TTR (p=0.032). Patients who experienced a GIB also had significantly more variability in their INR values than those who did not bleed (31.2% vs 25.8%, p=0.035) (Table 2). Conclusion: Both increased INR variability and decreased TTR are associated with increased rates of GIB in patients supported by LVADs. This is the first study to explore whether more INR variation puts patients with LVADs at greater risk of developing a GIB. Further prospective studies are warranted to further test this hypothesis.
476 Appropriate Management of Drug Interactions Results in Safe Use of Hepatitis C Therapies in Heart Transplant Recipients K. Boyle, R.E. Fowler, A. Pollack, C. Edmonds, J. Gray, J. Lindenfeld and K. Schlendorf. Vanderbilt University Medical Center, Nashville, TN.