Generalizability of Trial Data to Real-World Practice: An Analysis of The Society of Thoracic Surgeons Intermacs Database

Abstract

Background: Although the current wide-scale adoption of the HeartMate 3 left ventricular assist device can be attributed to favorable clinical trial outcomes, restrictive clinical trial eligibility criteria may result in lack of generalizability to real-world populations. We assessed the generalizability of left ventricular assist device clinical trial outcomes and evaluated the prognostic value of specific inclusion and exclusion criteria.

Methods: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Therapy With HeartMate 3 (MOMENTUM 3) eligibility criteria were applied to patients identified in The Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) who underwent HeartMate 3 implantation (n = 4610) between August 2017 and March 2020. Patients were categorized as trial-eligible or trial-ineligible and by number of ineligibility criteria. The effect of trial eligibility on mortality was estimated using Cox models.

Results: Indications for HeartMate 3 implant included destination therapy (n = 2827, 61%), bridge to candidacy (n = 969, 21%), and bridge to transplant (n = 702, 15%). A total of 1941 recipients (42%) were trial-ineligible, with 1245 (27%) meeting one ineligibility criterion, 470 (10%) meeting two, and 226 (5%) meeting three or more. Estimated 1-year mortality for trial-ineligible recipients was higher than for trial-eligible recipients (17% ± 1% vs 10% ± 1%, P < .001). Compared with trial-eligible patients, 1-year mortality was incrementally higher for patients meeting one ineligibility criterion (15% ± 1%), two criteria (16% ± 2%), and three or more criteria (30% ± 3%). Thrombocytopenia and elevated creatinine, bilirubin, and international normalized ratio in trial-ineligible patients were independently associated with increased mortality.

Conclusions: Despite differences in mortality, both trial-eligible and trial-ineligible HeartMate 3 recipients had excellent outcomes in real-world practice, suggesting future trial eligibility criteria could be expanded.