Differential effect of SGLT2 inhibitor on STEMI and non-STEMI warrants further study

The SGLT2 inhibitor canagliflozin is associated with a reduction in non-ST elevation MI (non-STEMI) but not ST elevation MI (STEMI) in patients with type 2 diabetes and high cardiovascular risk, Australian research shows.

A post hoc analysis of data from the CANVAS program and CREDENCE trial found 599 (4.1%) of 14,543 patients experienced an MI.

The study published in Cardiovascular Research, found there was no clear effect of canagliflozin on MI overall (HR 0.89; 95% CI 0.75, 1.05), with comparable results for the CANVAS program and CREDENCE trial.

However canagliflozin treatment was associated with a 22% lower rate of non-STEMI (HR 0.78; 95% CI 0.65, 0.95) and 55% higher risk of STEMI (HR 1.55; 95% CI 1.06, 2.27).

The study found the possible differential effect of canagliflozin on non-STEMI versus STEMI was driven primarily by the CANVAS Program.

No clear difference in hazard rates for fatal MI was observed between studies (HR 1.22; 95% CI 0.78, 1.93; p interaction=0.90).

In the CANVAS program, which compared 100 mg and 300 mg doses of canagliflozin, STEMI occurred less frequently with the higher dose compared to the lower dose (HR 0.49; 95% CI 0.28, 0.84).

“Whilst chance may be an explanation for the canagliflozin associated increase in STEMI observed in the CANVAS program, and we have not confirmed a mechanism for our findings, we believe that the observations in this combined cohort of >14,000 patients may spur important research in the field if confirmed in validation studies,” the researchers said.

They said STEMI was typically associated with total vessel occlusion at the site of plaque rupture, resulting from more organised fibrin-rich clot, compared to a more platelet dominated, non-occlusive picture for non-STEMI.

“It is biologically plausible that a drug therapy could have differential effects on plaque progression and rupture, versus thrombus formation once plaque rupture has occurred. This could shift the proportion of individuals that develop more organised fibrin-rich clots and differentially effect STEMI/non-STEMI presentations.”

The researchers including senior investigators Professor Gemma Figtree and Professor Bruce Neal from The George Institute, concluded that the differential effect on STEMI and non-STEMI warrants further investigation.

The study was supported by funding from Janssen.

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