Don't Miss a Beat: SELECT, DAPA-MI, & AHA 2023

The final flagship meeting on the calendar each year in the world of cardiology, the American Heart Association Scientific Sessions serves as a premier showcase for advancements and breakthroughs in cardiovascular medicine. The AHA Scientific Sessions 2023 continued this tradition, with the meeting serving as a platform for what many consider could be remembered as one of the most important trials, in regard to impact on public health, in decades.

In this special episode of Don’t Miss a Beat, hosts Muthiah Vaduganathan, MD, MPH, codirector of the Center for Implementation Science at Brigham and Women’s Hospital, and Steve Greene, MD, advanced heart failure specialist at the Duke Clinical Research Institute, sit down between sessions at AHA 2023 to discuss the landmark SELECT trial and its implications for care moving forward.

SELECT

The largest and longest trial of semaglutide in adults without type 1 or type 2 diabetes, the trial enrolled patients in a 1:1 ratio to either semaglutide 2.4 mg or placebo therapy. The trial’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. At the end of the trial, the mean change in body weight was –9.39% with semaglutide and –0.88% with placebo (estimated treatment difference, –8.51 percentage points; 95% CI, –8.75 to –8.27).

Results of the trial 17,000-patient trial suggested a primary event occurred among 6.5% of the semaglutide group and 8.0% of the placebo group (HR, 0.80; 95% Confidence interval [CI], 0.72 to 0.90; P <.001). Further analysis pointed to nonsignificant trends towards benefit for cardiovascular death (HR, 0.85; 95% CI, 0.71 to 1.01; P=.07), heart failure hospitalization or urgent medical visit (HR, 0.82; 95% CI, 0.71 to 0.96), all-cause mortality (HR, 0.81; 95% CI, 0.71 to 0.93), an HbA1c of 6.5% or greater (HR, 0.27; 95% CI, 0.24 to 0.31).

DAPA-MI

The DAPA-MI trial was launched with the intent of assessing whether use of dapagliflozin in patients with acute myocardial infarction might reduce the risk of adverse cardiovascular and metabolic outcomes. An international, registry-based, randomized, double-blind trial, the endeavor enrolled patients without prior diabetes or chronic heart failure presenting with acute myocardial infarction and impaired left ventricular systolic function.

Patients were randomized to daily dapagliflozin 10 mg or placebo. The trial was designed with a hierarchical composite of death, hospitalization for heart failure, nonfatal MI, atrial fibrillation/flutter, type 2 diabetes mellitus, New York Heart Association Functional Classification at the last visit, and body weight decrease of 5% or greater at the last visit using the win ratio analysis method as the primary outcome of interest.

Upon analysis, results pointed to significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% CI, 1.20 to 1.50; P <.001), but further analysis indicated there was no significant difference for the composite of time to cardiovascular death/hospitalization for heart failure in patients assigned to dapagliflozin and patients assigned to placebo (2.5% vs 2.6%; [HR, 0.95; 95% CI, 0.64 to 1.40]).

Disclosures:

Vaduganathan reports having received funding for consulting or research grants from Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others.

Greene reports having received funds for consulting or research grants from Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others.

References:

1. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes [published online ahead of print, 2023 Nov 11]. N Engl J Med. 2023;10.1056/NEJMoa2307563. doi:10.1056/NEJMoa2307563
2. James S, Erlinge D, Storey RF, et al. Dapagliflozin in myocardial infarction without diabetes or heart failure. NEJM Evidence. Published online 2023. doi:10.1056/evidoa2300286