Risk of Serious Adverse Events Associated With Serotonin Norepinephrine Reuptake Inhibitors Use in Older Adults, With a Focus on Chronic Kidney Disease.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 8,688
- 主要终点
- Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality.
研究概览
简要总结
This is a population-based retrospective, new-user design, active comparator cohort study assessing whether initiating a new outpatient prescription of high-dose serotonin norepinephrine reuptake inhibitors (SNRIs)-venlafaxine (>37.5-150 mg/day) or duloxetine (>30-120 mg/day), compared with low-dose SNRIs- venlafaxine (37.5 mg/day) or duloxetine (30 mg/day), is associated with an increased 30-day risk of serious adverse events among older adults with low kidney function (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73m2) who are not receiving dialysis and have no history of kidney transplantation.
The primary outcome is a 30-day composite of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality.
详细描述
Venlafaxine and duloxetine are serotonin norepinephrine reuptake inhibitors (SNRIs) commonly prescribed in older adults for depression, anxiety, and neuropathic pain.
Both medications are metabolized in the liver, and their elimination involves the renal route. The clearance of venlafaxine and duloxetine may be decreased in patients with low kidney function, leading to increased systemic exposure. Venlafaxine and duloxetine use in older adults with low kidney function may increase the risk of developing serious adverse events.
The most common measure to assess kidney function in routine clinical care is the estimated glomerular filtration rate (eGFR), expressed in lab reports as mL/min/1.73 m2. A normal eGFR is >90 mL/min/1.73 m2, and a value <45 mL/min/1.73 m2 is considered to be low.
The investigators aim to conduct a population-based cohort study among older adults with low kidney function in Ontario, comparing the risk of serious adverse events among those initiating high-dose SNRIs-venlafaxine (>37.5-150 mg/day) or duloxetine (>30-120 mg/day), versus low-dose SNRIs-venlafaxine (37.5 mg/day) or duloxetine (30 mg/day) in the outpatient setting. Secondary analyses will evaluate low-dose venlafaxine (37.5 mg/day) versus low-dose duloxetine (30 mg/day) and high versus lower doses within each drug.
Methods:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 66 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The cohort will include all older adults (≥66 years) with an eGFR <45 mL/min per 1.73 m2 (not receiving dialysis or having a history of kidney transplantation) who received a new outpatient prescription for oral venlafaxine or duloxetine between January 1, 2008, and December 1,
- •The age criterion is set to guarantee that individuals in this population have had at least one year of prior prescription drug coverage. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once.
排除标准
- •* Individuals with missing administrative database number, missing or invalid age (\<0 or \>105 years), missing or invalid sex, death on or before the index date, non-Ontario resident (for Ontario data), or non-Alberta residents (for Alberta data).
- •* Individuals less than 66 years of age on the index date.
- •* Those with evidence of any study drug prescription 180 days before the index date (to restrict to new users only).
- •* Individuals with more than one study drug prescription on the index date, as this complicates the ability to ascertain the prescribed dose accurately.
- •* Evidence of clinically non-meaningful venlafaxine or duloxetine doses (doses that are either too low or too high). The recommended dose range for venlafaxine is 37.5 to 150 mg per day, and for duloxetine is 30 to 120 mg per day.
- •* Individuals with end-stage renal disease, chronic dialysis, or a kidney transplant prior to the index date.
- •* Evidence with hospital discharge or emergency department visit in the two days prior to or on the index date to ensure a new outpatient prescription.
- •Individuals with no serum creatinine lab value in the 0-365 days prior to the index date.
- •* Individuals with unstable baseline kidney function: If the most recent serum creatinine test prior to the index date was an inpatient test \[ER or hospitalization\], and there is not at least one 'outpatient' serum creatinine in the year before test date 1, OR If the most recent prior serum creatinine test prior to the index date was an inpatient test \[ER or hospitalization\], and while there is at least 'outpatient' serum creatinine test in the year before, the most recent outpatient test prior to differs by an eGFR 10 mL/min/1.73 m2 or more from the value on \. In Ontario, it has been shown that outpatient serum creatinine measurements in the province, conducted on a single occasion, indicate stable values.
- •* The investigators restrict to the first prescription in individuals with more than one eligible prescription. The date of this prescription will be the index date (the date from which outcomes start being assessed).
研究组 & 干预措施
High-dose SNRIs-venlafaxine (>37.5-150 mg/day) or duloxetine (>30-120 mg/day)
Residents of Ontario, aged 66 years or older with low kidney function (an eGFR <45 mL/min per 1.73 m² but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for high-dose serotonin norepinephrine reuptake inhibitors-venlafaxine (>37.5-150 mg/day) or duloxetine (>30-120 mg/day) at an outpatient pharmacy under the Ontario Drug Benefit program from January 01, 2008, to December 01, 2025. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. If the investigators conduct the study in Alberta, the accrual period for Alberta will be determined.
干预措施: Venlafaxine or duloxetine (Drug)
Low-dose SNRIs- venlafaxine (37.5 mg/day) or duloxetine (30 mg/day)
Residents of Ontario, aged 66 years or older with low kidney function (an eGFR <45 mL/min per 1.73 m² but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for low-dose SNRIs- venlafaxine (37.5 mg/day) or duloxetine (30 mg/day) at an outpatient pharmacy under the Ontario Drug Benefit program from January 01, 2008, to December 01, 2025. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. If the investigators conduct the study in Alberta, the accrual period for Alberta will be determined.
干预措施: Venlafaxine or duloxetine (Drug)
结局指标
主要结局
Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality.
时间窗: Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.
30-day all-cause emergency department visit, all-cause hospitalization, and all-cause mortality will be combined into a composite measure. Only the first hospitalization or emergency department visit occurring after the cohort entry date will be considered.
次要结局
- Number of participants with 30-day all-cause emergency department visit.(Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.)
- Number of participants with 30-day all-cause hospitalization.(Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.)
- Number of participants with 30-day all-cause mortality.(Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.)
- 30-day composite outcome of a hospital encounter with fragility fracture, falls, hypotension, or syncope.(Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.)
- 30-day hospital encounter composite of atrial fibrillation/flutter, ventricular arrhythmia/sudden cardiac death, and other arrhythmia.(Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.)
- 30-day composite outcome of a hospital encounter with delirium or encephalopathy.(Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.)
- 30-day composite outcome of a hospital encounter with heart failure or myocardial infarction, or ischemic stroke.(Older adults exposed to high-dose venlafaxine or duloxetine vs low-dose venlafaxine or duloxetine will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.)