Dapagliflozin cuts MACE in patients with prior MI: CV label in the bag?
Dapagliflozin reduced the rate of MACE* by 16 percent in patients with type 2 diabetes (T2D) who had a prior myocardial infarction (MI) in one of DECLARE-TIMI 58 sub-analyses, boosting the drug’s chances of a label update for cardiovascular (CV) indication in addition to glucose lowering.
Currently, dapagliflozin is not indicated to reduce the risk of CV events, heart failure, or death in diabetes patients. With the positive results for MI, the focus is no longer just on the glucocentric advantage, but on the CV benefits of this SGLT2** inhibitor. Antidiabetes agents should be able to demonstrate CV safety, as mandated by the US FDA, in CV outcomes trials.
In the original DECLARE-TIMI 58 trial, dapagliflozin decreased the composite of CV death or hospitalizations for heart failure in patients with T2D, both in those with atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors. [N Engl J Med 2019;380:347–357]
In the current subanalysis, results of which were presented at ACC.19, dapagliflozin reduced both MACE (CV death, MI, or ischaemic stroke) and CV death or hospitalization in patients with diabetes and prior MI, with greater absolute benefit vs patients without MI. There was also a robust decrease in rates of type 2 MI, a condition caused by an imbalance between myocardial oxygen supply and demand. [Circulation 2019;doi:10.1161/CIRCULATIONAHA.119.039996]
Fewer deaths, MI, and stroke
In patients with prior MI, 15.2 percent of those in the dapagliflozin arm vs 17.8 percent in the placebo arm experienced MACE (hazard ratio [HR], 0.84, 95 percent confidence interval [CI], 0.72– 0.99; p=0.039), yielding an absolute risk reduction (ARR) of 2.6 percent. This ARR translates into a number needed to treat (NNT) of 39 over 4 years.
“Patients within the first 2 years after MI had the most striking MACE reduction with dapagliflozin [HR, 0.42; p=0.007],” said lead investigator Dr Remo Furtado from the TIMI Study Group, Brigham and Women’s Hospital in Boston, Massachusetts, US. This was apparently driven by lower rates of repeat or recurrent MI (HR, 0.78) regardless of MI type (HR, 0.80 for type 1; HR 0.64 for type 2).
“There was no effect in patients without prior MI. The same was true in patients with no prior MI but with established ASCVD.”
The rate for the composite outcome of CHD death, nonfatal MI, or sudden cardiac death was also lower with dapagliflozin (HR, 0.81). Taken individually, HR for CHD death was 0.84, for CV death it was 0.92, and for all-cause death, 0.83. As for ischaemic stroke, the risk was 17 percent lower in those taking dapagliflozin.
“Clearly, patients with T2D and prior MI derived important CV event reduction with dapagliflozin,” said Furtado. “These findings add new relevant information to recent guidelines, reinforcing that these patients should be strongly considered for SGLT2 inhibitors when selecting glucose-lowering agents.”
Implication to practice
He added that the findings bring new important data regarding selection therapies for treating T2D aimed not only at glycaemic control but also at CV event reduction. Whether this benefit extends to the acute phase of MI or to patients with prior MI but without T2D should be the subject of future studies.Dapagliflozin is approved for use as a monotherapy and as a combination therapy to improve glycaemic control in adult patients with T2D. If an expanded indication comes through, dapagliflozin can benefit a broader population of patients with T2D and CVD