PHILADELPHIA – Giving the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) to patients with acute myocardial infarction and impaired left ventricular systolic function but no diabetes or chronic heart failure significantly improved a composite of cardiovascular outcomes, a European registry-based randomized trial suggests.
In presenting these results from the DAPA-MI trial, Stefan James, MD, of Uppsala University (Sweden), noted that which the trial described as the hierarchical “win ratio” composite outcomes, compared with patients randomized to placebo plus standard of care.
Richard M. Kirkner/MDedge News
Dr. Stefan James
“The ‘win ratio’ tells us that there’s a 34% higher likelihood of patients having a better cardiometabolic outcome with dapagliflozin vs placebo in terms of the seven components,” James said in an interview. The win ratio was achieved in 32.9% of dapagliflozin patients versus 24.6% of placebo (P < .001).
Dr. James presented the results at the annual scientific sessions of the American Heart Association, and they were published online simultaneously in NEJM Evidence.
Lower-risk patients
DAPA-MI enrolled 4,017 patients from the SWEDEHEART and Myocardial Ischemia National Audit Project registries in Sweden and the United Kingdom, randomly assigning patients to dapagliflozin 10 mg or placebo along with guideline-directed therapy for both groups.
Eligible patients were hemodynamically stable, had an acute MI within 10 days of enrollment, and impaired left ventricular systolic function or a Q-wave MI. Exclusion criteria included history of either type 1 or 2 diabetes, chronic heart failure, poor kidney function, or current treatment with an SGLT2 inhibitor. Baseline demographic characteristics were similar between trial arms.
- The hierarchical seven primary endpoints were:
- Death, with cardiovascular death ranked first followed by noncardiovascular death
- Hospitalization because of heart failure, with adjudicated first followed by investigator-reported HF
- Nonfatal MI
- Atrial fibrillation/flutter event
- New diagnosis of type 2 diabetes
- New York Heart Association functional class at the last visit
- Drop in body weight of at least 5% at the last visit
The key secondary endpoint, Dr. James said, was the primary outcome minus the body weight component, with time to first occurrence of hospitalization for HF or cardiovascular death.
When the seventh factor, body weight decrease, was removed, the differential narrowed: 20.3% versus 16.9% (P = .015). When two or more variables were removed from the composite, the differences were not statistically significant.
For 11 secondary and exploratory outcomes, ranging from CV death or hospitalization for HF to all-cause hospitalization, the outcomes were similar in both the dapagliflozin and placebo groups across the board.
However, the dapagliflozin patients had about half the rate of developing diabetes, compared with the placebo group: 2.1 % versus 3.9%.
The trial initially used the composite of CV death and hospitalization for HF as the primary endpoint, but switched to the seven-item composite endpoint in February because the number of primary composite outcomes was substantially lower than anticipated, Dr. James said.
He acknowledged the study was underpowered for the low-risk population it enrolled. “But if you extended the trial to a larger population and enriched it with a higher-risk population you would probably see an effect,” he said.
“The cardiometabolic benefit was consistent across all prespecified subgroups and there were no new safety concerns,” Dr. James told the attendees. “Clinical event rates were low with no significant difference between randomized groups.”