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The concomitant use of second-generation antipsychotics and long-term antiretroviral therapy may be associated with increased cardiovascular risk.

ABSTRACT: To study the effect of concurrent use of second-generation antipsychotics (SGAs) on metabolic syndrome (MetS) components conferring increased cardiovascular risk in a sample of human immunodeficiency virus (HIV)-infected adults taking antiretroviral therapy (ART). A retrospective study of participants consecutively recruited at the UCSD HIV Neurobehavioral Research Program examined effects of combined ART and SGAs on body mass index (BMI), nonfasting serum lipids, diabetes mellitus (DM) incidence, and mean arterial pressure (MAP). Metabolic outcome variables and covariates were compared using t-tests, Chi-squared or Fisher's exact tests. Linear and logistic multivariable models explored metabolic outcomes for participants taking (SGA+) or not taking (SGA-) concomitant SGAs, after controlling for demographic and HIV disease- and ART-related covariates. Of 2229 HIV-infected participants, 12% (N=258) were treated with SGAs. In multivariable models adjusted for relevant covariates, the SGA+ group had significantly higher mean triglycerides, significantly higher odds of DM, significantly higher MAPs and marginally higher BMI. The use of SGAs in HIV-infected adults taking ART was independently associated with worse indicators of MetS and cardiovascular risk. Aggressive monitoring for the metabolic complications from concurrent SGA and ART is indicated in all patients receiving these medication combinations.

SUBMITTER: Ferrara M

PROVIDER: S-EPMC4082695 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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The concomitant use of second-generation antipsychotics and long-term antiretroviral therapy may be associated with increased cardiovascular risk.

Ferrara Maria M Umlauf Anya A Sanders Chelsea C Meyer Jonathan M JM Allen McCutchan John J Duarte Nichole N Hampton Atkinson Joseph J Grant Igor I Ellis Ronald J RJ

Psychiatry research 20140418 1-2

To study the effect of concurrent use of second-generation antipsychotics (SGAs) on metabolic syndrome (MetS) components conferring increased cardiovascular risk in a sample of human immunodeficiency virus (HIV)-infected adults taking antiretroviral therapy (ART). A retrospective study of participants consecutively recruited at the UCSD HIV Neurobehavioral Research Program examined effects of combined ART and SGAs on body mass index (BMI), nonfasting serum lipids, diabetes mellitus (DM) incidenc ...[more]

PMID: 24794030

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Project description:Objectives: To investigate the risk of cardiovascular events associated with concomitant use of stimulants and atypical antipsychotics (AAPs) among youth and evaluate whether AAP dose and duration of concomitant use modifies the risk. Methods: We used IQVIA PharMetrics® Plus data from 2006 to 2015 to construct a retrospective cohort of commercially-insured youth aged 5-17 years old who initiated a stimulant medication. Time-varying concomitant stimulant/AAP use was defined as current, past and no concomitant use based on person months. The primary time-varying Cox proportional hazard regression analysis evaluated the risk of cardiovascular events comparing current concomitant use with past and no concomitant use, adjusted for baseline cardiovascular risk. A secondary analysis assessed the risk of cardiovascular events comparing AAP daily doses (<1, 1-2, >2 mg) and duration (<3, 3-6, >6 months) of current concomitant use to no concomitant use. Cardiovascular outcomes included severe (i.e., stroke, acute myocardial infarction, ischemic heart disease) and less severe (i.e., angina pectoris, cardiac dysrhythmias, transient cerebral ischemia, hypertensive disease, tachycardia, palpitations, syncope). Results: For this cohort of 61,438 youths, the incidence rate of severe cardiovascular events was 0.18 per 10,000 person-months, and all events occurred in no concomitant use months. The risk of less severe cardiovascular events was significantly higher in current concomitant users compared with no [HR: 2.59 (95%CI: 1.72, 3.90)] and past [HR: 1.89 (95%CI: 1.10, 3.24)] concomitant users. Compared to no concomitant use, the risk of less severe cardiovascular events was significantly higher at all AAP daily doses [HR: <1 mg: 2.82 (95%CI: 1.72, 4.61); 1-2 mg: 2.22 (95%CI: 1.16, 4.25); >2 mg: 2.65 (95%CI: 1.50, 4.71)]. The risk of less severe cardiovascular events significantly elevated for all duration of use and was higher for <3 months of concomitant use [HR: <3 months: 3.45 (95%CI: 2.17, 5.47) relative to 3-6 months: 2.60 (95%CI: 1.29, 5.25) or >6 months: 2.61 (95%CI: 1.59, 4.30)]. Conclusions: Severe cardiovascular events are rare. Concomitant stimulant/AAP use elevates the risk of less severe cardiovascular events. Periodic heart rate or blood pressure monitoring for youth on stimulant/AAP treatment may be warranted.

Project description:Few controlled trials compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) regarding relapse prevention in schizophrenia. We conducted a systematic review/meta-analysis of randomized trials, lasting ?6 months comparing SGAs with FGAs in schizophrenia. Primary outcome was study-defined relapse; secondary outcomes included relapse at 3, 6 and 12 months; treatment failure; hospitalization; and dropout owing to any cause, non-adherence and intolerability. Pooled relative risk (RR) (±95% confidence intervals (CIs)) was calculated using random-effects model, with numbers-needed-to-treat (NNT) calculations where appropriate. Across 23 studies (n=4504, mean duration=61.9±22.4 weeks), none of the individual SGAs outperformed FGAs (mainly haloperidol) regarding study-defined relapse, except for isolated, single trial-based superiority, and except for risperidone's superiority at 3 and 6 months when requiring ?3 trials. Grouped together, however, SGAs prevented relapse more than FGAs (29.0 versus 37.5%, RR=0.80, CI: 0.70-0.91, P=0.0007, I(2)=37%; NNT=17, CI: 10-50, P=0.003). SGAs were also superior regarding relapse at 3, 6 and 12 months (P=0.04, P<0.0001, P=0.0001), treatment failure (P=0.003) and hospitalization (P=0.004). SGAs showed trend-level superiority for dropout owing to intolerability (P=0.05). Superiority of SGAs regarding relapse was modest (NNT=17), but confirmed in double-blind trials, first- and multi-episode patients, using preferentially or exclusively raw or estimated relapse rates, and for different haloperidol equivalent comparator doses. There was no significant heterogeneity or publication bias. The relevance of the somewhat greater efficacy of SGAs over FGAs on several key outcomes depends on whether SGAs form a meaningful group and whether mid- or low-potency FGAs differ from haloperidol. Regardless, treatment selection needs to be individualized considering patient- and medication-related factors.

Project description:BackgroundSchizophrenia is a severe condition that affects approximately 1% of the population. Certain elements of antipsychotic treatment can only be examined in large population, thus the need for population-based real-world analyses has been increasing.Patients and methodsHungarian National Health Fund database includes all healthcare data of the population of Hungary. All patients diagnosed with schizophrenia between 01.01.2006 and 31.12.2015 were included in the study. We analyzed all patients with newly initiated second-generation antipsychotic during the inclusion period (01.01.2012-31.12.2013). Patients were followed for 2 years. All-cause treatment discontinuation served as the primary outcome of the study. Patients with newly initiated long-acting injectable treatments were further investigated in stratified analyses based on their previous treatment.Results106,624 patients had schizophrenia diagnosis during the study period. 12,232 patients met the inclusion criteria for newly initiating second-generation antipsychotic during the inclusion period. The proportion of patients still on treatment after 1 year for oral treatments varied between 17% (oral risperidone) and 31% (oral olanzapine) while the analogous data for long acting injectables were between 32% (risperidone long acting) and 64% (paliperidone long acting one monthly). The 2-year data were similarly in favor of long-actings. Median time to discontinuation in the oral group varied between 57 days (clozapine) and 121 days (olanzapine). The median time to discontinuation for long-actings was significantly longer: between 176 and 287 days; in case of paliperidone long acting, median was not reached during the observation period. Patients receiving long-acting treatment switched from another long-acting remained on the newly initiated treatment significantly longer than those switched from orals.ConclusionOur results indicate the superiority of second generation long-acting antipsychotics with regard to rates of treatment discontinuation and periods of persistence to the assigned medication.

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The concomitant use of second-generation antipsychotics and long-term antiretroviral therapy may be associated with increased cardiovascular risk.

Publications

The concomitant use of second-generation antipsychotics and long-term antiretroviral therapy may be associated with increased cardiovascular risk.

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