Investigators are building an empirical evidence base for real-world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to assess the comparative effectiveness of tirzepatide vs semaglutide after emulating the pivotal RCTs of each drug used to support regulatory approval in heart failure with preserved ejection fraction (SUMMIT and STEP-HFpEF DM trials).This comparative effectiveness target trial described below draws from eligibility criteria from the SUMMIT and STEP-HFpEF DM trials. Although many features of the target trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the target trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. The database study will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs semaglutide on the composite end point of all-cause mortality or heart failure hospitalization. Clinical guidelines during the study period recommended both agents for the same indications of glucose lowering and weight reduction. Indication for heart failure with preserved ejection fraction has not been granted for both drugs during the study period.
Study Type
OBSERVATIONAL
Enrollment
28,118
New use of tirzepatide dispensing claim is used as the exposure.
New use of semaglutide dispensing claim is used as the reference.
Brigham and Women's Hospital
Boston, Massachusetts, United States
Composite of all-cause mortality or heart failure hospitalization
To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or heart failure hospitalization in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Composite of all-cause mortality or all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting).
To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or worsening heart failure events in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).
To evaluate the comparative effect of tirzepatide vs semaglutide on worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting) in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Intravenous diuretic therapy in an urgent care setting
To evaluate the comparative effect of tirzepatide vs semaglutide on intravenous diuretic therapy in an urgent care setting in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Hospitalization for heart failure
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To evaluate the comparative effect of tirzepatide vs semaglutide on hospitalization for heart failure in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
All-cause mortality
To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Urinary tract infection
To evaluate the comparative effect of tirzepatide vs semaglutide on urinary tract infection in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Serious bacterial infection
To evaluate the comparative effect of tirzepatide vs semaglutide on serious bacterial infection in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Gastrointestinal adverse events
To evaluate the comparative effect of tirzepatide vs semaglutide on gastrointestinal adverse events in patients with heart failure with preserved ejection fraction.
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)