Dataset Information

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

ABSTRACT: STUDY OBJECTIVE:To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women. DESIGN:Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]). PARTICIPANTS:A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV. MEASUREMENTS AND MAIN RESULTS:Data on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p<0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4+ cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p<0.0001). Although use of benzodiazepines and conditional QT interval-prolonging medications were associated with increased risk of non-AIDS mortality (HR 1.32 and 1.25, respectively), the effect was not statistically significant (p>0.05). CONCLUSION:In this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population.

SUBMITTER: Tamraz B

PROVIDER: S-EPMC7000174 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

Tamraz Bani B Reisner Lori L French Audrey L AL King Samuel T ST Fischl Margaret A MA Ofotokun Igho I Kashuba Angela A Milam Joel J Murphy Kerry K Augenbraun Michael M Liu Chenglong C Finley Patrick R PR Aouizerat Bradley B Cocohoba Jennifer J Gange Stephen S Bacchetti Peter P Greenblatt Ruth M RM

Pharmacotherapy 20190813 9

<h4>Study objective</h4>To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women.<h4>Design</h4>Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]).<h4>Participants</h4>A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) ...[more]

PMID: 31332819

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Project description:RATIONALE, AIMS, AND OBJECTIVES:Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening. METHOD:The Atherosclerosis Risk in Communities study assessed 15 792 participants with a resting, standard 12-lead electrocardiogram and ?1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we excluded participants with QRS ? 120 milliseconds (n = 2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36 602 person-visit observations for 14 160 cohort members controlling for age ? 65 years, female sex, left ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person. RESULTS:Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of risk factors, Known QTPMs and ?2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ?2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone. CONCLUSION:Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors.

Project description:ImportanceQT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown.ObjectiveTo evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death.Design, setting, and participantsThis prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019.ExposureQT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high).Main outcomes and measuresDeath due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause.ResultsA total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P?<?.001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P?=?.04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P?=?.01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P?=?.02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P?=?.02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P?=?.001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group.Conclusions and relevanceThese findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

Dataset Information

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

Publications

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

Similar Datasets

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