Publications

BACKGROUND: Although mitral transcatheter edge-to-edge repair (MTEER) was approved for secondary mitral regurgitation after the COAPT trial, findings of other MTEER trials have been mixed, raising questions about the applicability of the COAPT results to contemporary clinical practice.

OBJECTIVES: We used transportability methods to estimate the treatment effects of COAPT trial interventions applied to 2 target populations: 1) trial-eligible patients representative of U.S. clinical practice; and 2) treatment-candidate patients with secondary mitral regurgitation representative of U.S. clinical practice, regardless of trial eligibility.

METHODS: We identified patients from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry who were treated with MTEER for secondary mitral regurgitation from March 14, 2019 to September 30, 2023. To select trial-eligible individuals, we applied COAPT trial eligibility criteria to the TVT Registry sample. We used inverse odds of participation weighting to standardize patient-level COAPT data to the data distribution of each target population sample and estimated treatment-specific outcomes. The primary outcome was heart failure hospitalization at 2 years. We also examined 10 secondary outcomes, including all-cause death.

RESULTS: Our analyses included 614 COAPT trial patients and 15,275 TVT Registry patients, of which 7,289 were COAPT trial-eligible. Trial-eligible TVT Registry patients were less likely to have ischemic cardiomyopathy (34.1% vs 60.8%) and more likely to have 4+ mitral regurgitation (79.4% vs 47.9%) compared with trial patients. We estimated that compared with medical therapy alone, MTEER in conjunction with other COAPT interventions (eg, optimization of medical therapy) in the trial-eligible population would result in 2-year absolute risk reductions of 17.0% for heart failure hospitalizations (95% CI: -28.7% to -5.7%) and 15.4% for all-cause death (95% CI: -26.6% to -5.2%), effect sizes similar to those estimated in the trial (P for difference between the trial and target populations >0.05 for both outcomes). The estimated treatment effect for heart failure hospitalizations in the broader treatment-candidate target population was also similar to that in the COAPT trial (P for difference = 0.90).

CONCLUSIONS: Although COAPT trial patients had different baseline characteristics than patients undergoing MTEER in contemporary U.S. practice, we estimated that treatment effects would be similar had real-world patients received COAPT trial interventions, under the assumptions required for transportability (eg, conditional exchangeability across data sources, positivity of trial participation).

It has long been accepted that observational analyses have an important role in evaluating use patterns and assessing the safety of different treatments, including cardiovascular devices, in clinical practice. With the proliferation of large electronic databases, there has been increasing interest in using observational analyses to also examine the comparative effectiveness of devices. However, these analyses are often met with skepticism because of concerns about whether they can generate credible evidence about causal effects. This is in part a result of the difficulty in meeting the assumptions necessary to interpret observational associations as causal effects and of the wide variability in analytic rigor. In this review, we outline frameworks and review methods for using observational analyses to answer questions about the effectiveness and safety of cardiovascular devices. We highlight the target trial framework as a practical tool for guiding observational comparative effectiveness analyses. We illustrate how the framework allows investigators planning and conducting observational analyses to organize their activities as responses to 3 prompting questions. First, what is the research question of the study (ie, "What do we want?")? Second, what are the resources-including background knowledge, research concepts, principles and methods, and available data-that can be brought to bear on the research question (ie, "What do we have?")? And third, what specific steps should be taken to use the available resources to answer the research question (ie, "What do we do?")? We focus our exposition on the evaluation of cardiovascular devices, for which randomized trial data are often limited and there is a strong need for real-world evidence. In this setting, real-world evidence is usually derived from observational comparisons of the treatment of interest with relevant comparator groups using data captured during routine care. A principled approach to the planning and conduct of observational analyses can improve the quality of real-world evidence generation and ensure that the results of observational studies on medical devices can support meaningful conclusions about the risks and benefits of new devices.

BACKGROUND: Veterans are at an increased cardiovascular risk compared to age- and sex-matched non-Veterans. Cardiac rehabilitation (CR) can improve outcomes in cardiovascular disease, but its use in men and women Veterans is not well understood.

OBJECTIVES: This study aimed to examine CR participation by sex and socioeconomic status among Veterans.

METHODS: The authors conducted a retrospective cohort study from January 1, 2021, to December 31, 2023, using a national electronic health record database. The primary outcome was participation in at least 1 CR session among patients within 1 year of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery. Multivariable logistic regression models accounted for patient-level (demographics, medical/psychiatric comorbidities) and community-level factors. Area deprivation indices (ADIs) (analyzed as quartiles) assessed socioeconomic status.

RESULTS: Among 82,496 CR-eligible Veterans (3.6% women), CR participation was low (10.4%) and similar by sex (women = 10.2%, men = 10.4%). Women Veterans did not differ significantly in CR participation compared to men Veterans after adjusting for patient-level and community-level characteristics, including age, race, cardiac and comorbidities, mental health risk factors, rural-urban status, and ADI (adjusted OR: 0.90; 95% CI: 0.79-1.03; P = 0.121). Veterans in the most deprived ADI quartile were less likely to participate vs the least deprived quartile (adjusted OR: 0.82; 95% CI: 0.75-0.89; P < 0.001).

CONCLUSIONS: CR participation among U.S. Veterans remains low, far below that of the Medicare population (10.4% vs 28%), with no significant differences in initiation by sex. However, low socioeconomic status is associated with decreased uptake. Further research is needed to explore innovative, Veteran-specific CR delivery models.

IMPORTANCE: The prevalence of obesity and cardiovascular-kidney-metabolic (CKM) syndrome continues to rise. Indications for novel CKM therapies, including glucagonlike peptide 1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and nonsteroidal mineralocorticoid antagonists (nsMRAs) continue to expand, yet the proportion of adults meeting expanded indications, including for multiple medications remains unclear.

OBJECTIVE: To examine proportion of adults meeting US Food and Drug Administration (FDA)-approved indications for GLP1-RAs, SGLT2is, and nsMRAs across national survey, community-based, and ambulatory health care samples.

DESIGN, SETTING, AND PARTICIPANTS: This study used a representative cross-sectional survey of US adults (National Health and Nutrition Examination Survey [NHANES], weighted 245 million; mean [SD] age, 47 [18] years; 126.8 million [52%] female), 5 pooled community-based cohort studies (the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Prevention of Renal and Vascular Endstage Disease Study, the Atherosclerosis Risk in Communities Study, and the Cardiovascular Health Study; n = 30 929; mean [SD] age, 63 [14] years; 16 749 [54%] female), and 2 ambulatory health care samples (the Beth Israel Deaconess Medical Center cohort [BIDMC], n = 84 714; mean [SD] age, 46 [17] years; 51 113 [60%] female] and the Mass General Brigham cohort [MGB], n = 362 485; mean [SD] age, 48 [17] years; 227 206 [61%] female). Data were analyzed from November 2024 to November 2025.

EXPOSURES: FDA-approved indications for GLP-1RAs, SGLT2is, and nsMRAs.

MAIN OUTCOMES AND MEASURES: Medication class eligibility within each study sample.

RESULTS: The proportion of individuals who met current FDA-approved indications for 1 or more CKM medication was 60% in NHANES (representing 148 million US adults), 61% in the pooled cohorts, 42% in the BIDMC ambulatory cohort, and 46% in the MGB ambulatory cohort. Eligibility for GLP-1RA therapy was most common, with 56% (representing 137.1 million US adults) in NHANES, 49% in the pooled cohorts, 41% in the BIDMC cohort, and 46% in the MGB cohort. This was followed by SGLT2i therapy (24% [57.9 million] in NHANES, 33% in the pooled cohorts, 14% for both BIDMC and MGB) and nsMRA (5% [11.7 million] in NHANES, 5% in the pooled cohorts, and 1% to 2% in ambulatory samples). Overlapping eligibility for multiple classes was common, with 12% to 17% for GLP1-RA and SGLT2i therapies and 1% to 5% for all 3 classes (an estimated 11.7 million US adults in NHANES).

CONCLUSIONS AND RELEVANCE: This study found that up to 61% of adults met FDA-approved indications for at least 1 of 3 novel CKM therapy classes. This represents an estimated 148 million US adults, including 11.7 million US adults with potential FDA indications for triple therapy, highlighting the urgent need to optimize implementation and utilization of CKM syndrome therapies.