ANTIPSYCHOTIC USE AND RISK OF ACUTE RESPIRATORY FAILURE IN PATIENTS WITH COPD

Abstract

SESSION TITLE: COPD Assessment Tools and ComorbiditiesSESSION TYPE: Rapid Fire Original InvPRESENTED ON: 10/17/2022 12:15 pm - 1:15 pmPURPOSE: Background: Case reports and observational studies describe severe respiratory events associated with antipsychotic use.Purpose: To determine whether antipsychotic use is associated with an increased risk of acute respiratory failure (ARF) requiring invasive mechanical ventilation in patients with chronic obstructive pulmonary disease (COPD).METHODS: We conducted a case-crossover study among US Medicare Fee-for-Service beneficiaries with COPD diagnosed with ARF requiring invasive mechanical ventilation between January 2007 and December 2019. We excluded beneficiaries with prior ARF, active cancer treatment, select conditions that may cause ARF, use of antipsychotics as anti-emetics or by a non-oral route, and those hospitalized or residing in a skilled nursing facility (Part A) during the case and/or control periods. We ascertained antipsychotic exposure in the case and control windows, defined as -1 to -14 and -75 to -88 days prior to admission, respectively. We used conditional logistic regression adjusted for use of select CNS depressants, oral corticosteroids, COPD medications, presence of delirium, and ARF background rate to calculate adjusted odd ratios (aORs) of ARF with use of antipsychotics in the case period compared to the control period. To assess effect modification, we performed analyses in subgroups defined by age, sex, race, dementia, heart failure, home oxygen use, frailty score, reason for entering Medicare, and nursing home residence.RESULTS: We identified 145,018 cases (mean age 69.4 years, 57.2% female). Of these, 2,003 had antipsychotic use only during the risk window and 1,728 only during the control window. The aOR of antipsychotic use within 14 days before ARF was 1.13 (1.06, 1.20). Risk was not increased in patients below age 75 years (aOR 18-49 years: 1.01 [0.85, 1.20]; 50-64 years: 1.03 [0.93, 1.15]; 65-74 years: 1.12 [0.98, 1.28]), but was increased in patients ages 75-84 years (aOR: 1.37 [1.17, 1.60]) and 85+ years (aOR: 1.50 [1.20, 1.89]). The risk of ARF with antipsychotic use was also increased in patients residing in nursing homes and with high frailty scores.CONCLUSIONS: Recent antipsychotic use by older Medicare beneficiaries with COPD was associated with increased risk of ARF. Ongoing efforts include evaluating the interaction of age with other relevant covariates, as well in certain subgroups, and addressing potential concerns of violation of intermittent use and exposure time-trend assumptions and persistent user bias. This abstract reflects the views of the authors and should not be construed to represent FDA’s views or policies.CLINICAL IMPLICATIONS: Recent antipsychotic use may increase the risk of acute respiratory failure requiring intubation and mechanical ventilation in older patients with COPD.DISCLOSURES: No relevant relationships Added 04/01/2022 by Armen Avagyan, value=SalaryRemoved 04/01/2022 by Armen AvagyanSpouse has direct stock ownership relationship with Abbvie Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=DividendsSpouse has direct ownership of stock relationship with Bristol Myers Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=DividendsSpouse has direct ownership of stock relationship with Johnson & Johnson Please note: 2013-present Added 04/12/2022 by Amy Brehm, value=DividendsNo relevant relationships by David GrahamNo relevant relationships by Jeff KelmanNo relevant relationships by Hyeseung LeeNo relevant relationships by Kira LeishearNo relevant relationships by anchi loNo relevant relationships by Thomas MaCurdyNo relevant relationships by Andrew MosholderNo relevant relationships by Silvia Perez-VilarNo relevant relationships Added 03/30/2022 by Elizabeth Smith, value=SalaryRemoved 03/30/2022 by Elizabeth SmithNo relevant relationships by Marc StoneNo relevant relationships by Michael WerneckeNo relevant relationships by yueqin zhao SESSION TITLE: COPD Assessment Tools and Comorbidities SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Background: Case reports and observational studies describe severe respiratory events associated with antipsychotic use. Purpose: To determine whether antipsychotic use is associated with an increased risk of acute respiratory failure (ARF) requiring invasive mechanical ventilation in patients with chronic obstructive pulmonary disease (COPD). METHODS: We conducted a case-crossover study among US Medicare Fee-for-Service beneficiaries with COPD diagnosed with ARF requiring invasive mechanical ventilation between January 2007 and December 2019. We excluded beneficiaries with prior ARF, active cancer treatment, select conditions that may cause ARF, use of antipsychotics as anti-emetics or by a non-oral route, and those hospitalized or residing in a skilled nursing facility (Part A) during the case and/or control periods. We ascertained antipsychotic exposure in the case and control windows, defined as -1 to -14 and -75 to -88 days prior to admission, respectively. We used conditional logistic regression adjusted for use of select CNS depressants, oral corticosteroids, COPD medications, presence of delirium, and ARF background rate to calculate adjusted odd ratios (aORs) of ARF with use of antipsychotics in the case period compared to the control period. To assess effect modification, we performed analyses in subgroups defined by age, sex, race, dementia, heart failure, home oxygen use, frailty score, reason for entering Medicare, and nursing home residence. RESULTS: We identified 145,018 cases (mean age 69.4 years, 57.2% female). Of these, 2,003 had antipsychotic use only during the risk window and 1,728 only during the control window. The aOR of antipsychotic use within 14 days before ARF was 1.13 (1.06, 1.20). Risk was not increased in patients below age 75 years (aOR 18-49 years: 1.01 [0.85, 1.20]; 50-64 years: 1.03 [0.93, 1.15]; 65-74 years: 1.12 [0.98, 1.28]), but was increased in patients ages 75-84 years (aOR: 1.37 [1.17, 1.60]) and 85+ years (aOR: 1.50 [1.20, 1.89]). The risk of ARF with antipsychotic use was also increased in patients residing in nursing homes and with high frailty scores. CONCLUSIONS: Recent antipsychotic use by older Medicare beneficiaries with COPD was associated with increased risk of ARF. Ongoing efforts include evaluating the interaction of age with other relevant covariates, as well in certain subgroups, and addressing potential concerns of violation of intermittent use and exposure time-trend assumptions and persistent user bias. This abstract reflects the views of the authors and should not be construed to represent FDA’s views or policies. CLINICAL IMPLICATIONS: Recent antipsychotic use may increase the risk of acute respiratory failure requiring intubation and mechanical ventilation in older patients with COPD. DISCLOSURES: No relevant relationships Added 04/01/2022 by Armen Avagyan, value=Salary Removed 04/01/2022 by Armen Avagyan Spouse has direct stock ownership relationship with Abbvie Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=Dividends Spouse has direct ownership of stock relationship with Bristol Myers Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=Dividends Spouse has direct ownership of stock relationship with Johnson & Johnson Please note: 2013-present Added 04/12/2022 by Amy Brehm, value=Dividends No relevant relationships by David Graham No relevant relationships by Jeff Kelman No relevant relationships by Hyeseung Lee No relevant relationships by Kira Leishear No relevant relationships by anchi lo No relevant relationships by Thomas MaCurdy No relevant relationships by Andrew Mosholder No relevant relationships by Silvia Perez-Vilar No relevant relationships Added 03/30/2022 by Elizabeth Smith, value=Salary Removed 03/30/2022 by Elizabeth Smith No relevant relationships by Marc Stone No relevant relationships by Michael Wernecke No relevant relationships by yueqin zhao