Pulmonary Arterial Hypertension
Conditions
Brief summary
This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication.
Detailed description
This is a non-randomized, non-interventional study that is part of the DREAM Study of Brigham and Women's Hospital. DREAM is led by Dr. Madhav Thambisetty, MD, PhD, Chief of the Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA) intramural research program. This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication using healthcare claims data.
Interventions
DRUGPDE5 inhibitor
PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group.
DRUGEndothelin Receptor Antagonists
Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) claim is used as the reference group.
Sponsors
National Institute on Aging (NIA)
Rutgers University
Johns Hopkins University
Brigham and Women's Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Inclusion criteria
Please see https://docs.google.com/spreadsheets/d/19NwmDi8xwWjzXqhSLPDTg4CKHt5UDQXuwCnZwY8jCS8/edit?usp=sharing or Appendix A for full code and algorithm definitions. Medicare timeframe: 2008 to 2018 (end of data availability). Inclusion Criteria: * 1\. Aged \> 65 years on the index date * 2\. No prior use of PDE5 inhibitors (sildenafil, tadalafil) and endothelin receptor antagonists (bosentan, ambrisentan, macitentan) anytime prior to cohort entry date * 3\. Enrollment in Medicare Part A, B, and D with no HMO coverage for 365 days prior to and including cohort entry date
Exclusion criteria
* 1\. Prior history of dementia measured anytime prior to cohort entry date * 2\. No prior history of pulmonary arterial hypertension recorded in the 365 days prior to cohort entry date * 3\. Prior history of nursing home admission in the 365 days prior to the cohort entry date
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Dementia Onset | Median follow up times: 1) 168 days (exp), 151 days (ref) 2) 693 days (exp), 720 days (ref) 3) 382 days (exp), 358 days (ref) 4) 169 days (exp), 151 days (ref) | Time to dementia onset includes: Alzheimer's disease, vascular dementia, senile, presenile, or unspecified dementia, or dementia in other diseases classified elsewhere. Please refer to uploaded protocol for full definition. Analysis 1-'as-treated' follow-up approach: In this approach, we followed patients from cohort entry until treatment discontinuation or switch to the comparator treatment, insurance disenrollment, death, or administrative endpoint (December 2018). Treatment discontinuation was defined as occurring 90 days after the expected days supply. of the most recently filled prescription to accommodate suboptimal adherence during treatment periods. Analysis 2-'as-started' follow-up approach incorporating a 6-month 'induction' period. Analysis 3-incorporating a 6-month 'symptoms to diagnosis' period Analysis 4-high-specificity outcome definition Study accessed Medicare files (Jan 2008-Dec 2018) between September 1, 2021 to October 4, 2022. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PDE5 Inhibitors Exposure group
PDE5 inhibitor: PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group. | 2,888 |
| Endothelin Receptor Antagonists Reference group
Endothelin Receptor Antagonists: Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) claim is used as the reference group. | 2,888 |
| Total | 5,776 |
Baseline characteristics
| Characteristic | PDE5 Inhibitors | Endothelin Receptor Antagonists | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2888 Participants | 2888 Participants | 5776 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 73.87 years STANDARD_DEVIATION 6.43 | 73.84 years STANDARD_DEVIATION 6.15 | 73.86 years STANDARD_DEVIATION 6.65 |
| Dementia risk factors Anxiety | 466 Participants | 465 Participants | 931 Participants |
| Dementia risk factors Bipolar disorder | 28 Participants | 32 Participants | 60 Participants |
| Dementia risk factors Coronary artery disease | 2136 Participants | 2150 Participants | 4286 Participants |
| Dementia risk factors Depression | 515 Participants | 537 Participants | 1052 Participants |
| Dementia risk factors Diabetes | 1180 Participants | 1145 Participants | 2325 Participants |
| Dementia risk factors Hypertension | 2587 Participants | 2595 Participants | 5182 Participants |
| Dementia risk factors Obesity | 911 Participants | 918 Participants | 1829 Participants |
| Dementia risk factors Schizophrenia | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Asian | 51 Participants | 53 Participants | 104 Participants |
| Race/Ethnicity, Customized Black | 421 Participants | 411 Participants | 832 Participants |
| Race/Ethnicity, Customized Hispanic | 48 Participants | 46 Participants | 94 Participants |
| Race/Ethnicity, Customized Native American | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Other | 49 Participants | 41 Participants | 90 Participants |
| Race/Ethnicity, Customized Unknown | 15 Participants | 15 Participants | 30 Participants |
| Race/Ethnicity, Customized White | 2293 Participants | 2311 Participants | 4604 Participants |
| Sex: Female, Male Female | 1999 Participants | 1990 Participants | 3989 Participants |
| Sex: Female, Male Male | 889 Participants | 898 Participants | 1787 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 327 / 2,888 | 407 / 2,888 |
| other Total, other adverse events | 0 / 2,888 | 0 / 2,888 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Time to Dementia Onset
Time to dementia onset includes: Alzheimer's disease, vascular dementia, senile, presenile, or unspecified dementia, or dementia in other diseases classified elsewhere. Please refer to uploaded protocol for full definition. Analysis 1-'as-treated' follow-up approach: In this approach, we followed patients from cohort entry until treatment discontinuation or switch to the comparator treatment, insurance disenrollment, death, or administrative endpoint (December 2018). Treatment discontinuation was defined as occurring 90 days after the expected days supply. of the most recently filled prescription to accommodate suboptimal adherence during treatment periods. Analysis 2-'as-started' follow-up approach incorporating a 6-month 'induction' period. Analysis 3-incorporating a 6-month 'symptoms to diagnosis' period Analysis 4-high-specificity outcome definition Study accessed Medicare files (Jan 2008-Dec 2018) between September 1, 2021 to October 4, 2022.
Time frame: Median follow up times: 1) 168 days (exp), 151 days (ref) 2) 693 days (exp), 720 days (ref) 3) 382 days (exp), 358 days (ref) 4) 169 days (exp), 151 days (ref)
Population: Study cohort after 1:1 propensity score matching
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PDE5 Inhibitors | Time to Dementia Onset | Analysis 1 | 17.9 Incidence rate per 1000 person year |
| PDE5 Inhibitors | Time to Dementia Onset | Analysis 2 | 19.8 Incidence rate per 1000 person year |
| PDE5 Inhibitors | Time to Dementia Onset | Analysis 3 | 15.1 Incidence rate per 1000 person year |
| PDE5 Inhibitors | Time to Dementia Onset | Analysis 4 | 5.2 Incidence rate per 1000 person year |
| Endothelin Receptor Antagonists | Time to Dementia Onset | Analysis 4 | 4.7 Incidence rate per 1000 person year |
| Endothelin Receptor Antagonists | Time to Dementia Onset | Analysis 1 | 18.8 Incidence rate per 1000 person year |
| Endothelin Receptor Antagonists | Time to Dementia Onset | Analysis 3 | 22.6 Incidence rate per 1000 person year |
| Endothelin Receptor Antagonists | Time to Dementia Onset | Analysis 2 | 19.9 Incidence rate per 1000 person year |