A study with a unique trial design and a newer endpoint shows Farxiga can improve cardiometabolic outcomes in a subset of patients.
In a subset of patients with myocardial infarction and impaired left ventricular systolic function, Farxiga (dapagliflozin) was able to improve cardiometabolic outcomes. This is finding of a registry-based study presented today at the American Heart Association Scientific Sessions meeting in Philadelphia.
The cardiometabolic benefit was consistent across subgroups and clinical event rates were low with no significant difference between randomized groups, study author Stefan James, Ph.D., professor of cardiology at Uppsala University and scientific director of Uppsala Clinical Research Center, said during the presentation. Patients who received Farxiga had low rates of cardiovascular disease and hospitalization from heart failure, and the study met the composite endpoints.
Farxiga is an SGLT2 inhibitor. The SGLT class, originally approved to treat type 2 diabetes, has revolutionized the oral treatment of heart disease. Another SGLT2 on the market is Boehringer Ingelheim’s Jardiance (empagliflozin). In May 2023, Farxiga was approved in the United States to reduce the risk of cardiovascular (CV) death and hospitalization for heart failure (hHF). Developed by AstraZeneca, Farxiga is also approved to improve blood sugar in those with type 2 diabetes and to treat those with chronic kidney disease.
This trial of Farxiga, DAPA-MI, was a hybrid of registry/randomized controlled phase 3 trial. It enrolled more than 4,000 patients without diabetes or heart failure, with 2,019 patients receiving Farxiga plus standard of care and 1,998 patients receiving placebo plus standard of care. The main inclusion criteria were myocardial infarction and impaired left ventricular systolic function. Also known as heart attack, myocardial infarction is caused by decreased blood flow to the heart. If not treated quickly, it can lead to heart damage and even death.
In DAPA-MI, the primary composite endpoints included first cardiovascular death, hospitalization drug to heart failure, nonfatal myocardial infarction, atrial fibrillation, new diagnosis of diabetes, NYHA function class and weight decrease.
The trial used a newer endpoint — the win ratio, a method for reporting composite endpoints that gives priority to certain events. Patients in these trials are matched based on risk profiles and events are compared among the pairs and assigned a “win” if they meet the endpoint.
In DAPA-MI, 32.9% of patients experienced a “win” for all components in the primary outcome, compared with 24.6% in the placebo group. For all of the secondary endpoints, 20% of patients experienced a “win” compared with 16.9% in the placebo group.
Among key secondary endpoints, only 2.5% of patients in the Farxiga group experienced a cardiovascular death or hospitalization for heart failure, and 3.4% of patients treated with Farxiga experienced a major adverse cardiovascular event, such as myocardial infarction, stroke or cardiovascular death.
“Investigators [in DAPA-MI] met the revised primary win ratio endpoint of cardiometabolic outcomes, but it was driven by nontraditional cardiovascular outcome trials components. It was truly underpowered to evaluate traditional heart cardiovascular endpoints with no favorable signals were observed,” Stephen D. Wiviott, M.D., TIMI Study Group, Cardiovascular Division at Brigham and Women’s Hospital and Harvard Medical School.
He said the results from DAPA-MI support the safe use of Farxiga in a subset of patients with myocardial infarction. But further study of Farxiga in patients with diabetes and chronic kidneys — who were excluded from this study — are needed.
This type of hybrid trial with a randomized trial within a registry, however, holds promise for efficient patient recruitment and outcomes assessment. These trials use registries as a platform for records, data collection, randomization, and follow-up.
Wiviott suggests that the hybrid trial could be leveraged in the future for the registration trials. They offer an opportunity to conduct trials at a fraction of the cost and are pragmatic way to answer research questions.