Canagliflozin May Not Reduce Myocardial Infarction Risk in Patients With Type 2 Diabetes

human heart
A heart attack (myocardial infarction) is usually caused by a blood clot, which stops the blood flowing to a part of your heart muscle.
Treatment with canagliflozin may not significantly lower risk for myocardial infarction among patients with type 2 diabetes and comorbid chronic kidney disease or among patients with diabetes who have a history of or have a high risk for CVD.

Treatment with canagliflozin may not provide a significant reduction in myocardial infarction (MI) risk among patients with type 2 diabetes (T2D) and comorbid chronic kidney disease (CKD) or among patients with diabetes who have a history of or have a high risk for cardiovascular disease (CVD), a study in Cardiovascular Research suggested.

The study was a pooled analysis of 14,543 patients from the CANVAS program and CREDENCE trial. The CANVAS program included patients with T2D who had either a history of or were at high risk for CVD whereas the CREDENCE trial included patients with T2D and CKD. The pooled analysis of the 2 cohorts examined treatment with either 100 mg or 300 mg canagliflozin vs placebo with regard to the incidence of MI.

A total of 599 patients experienced an MI over a median follow-up period of 2.5 years. The MI event was fatal in 83 patients. The first MI events included 128 ST-segment elevation myocardial infarctions (STEMIs), 431 non-STEMIs, and 40 undetermined events.

Patients who experienced an MI were generally older (mean, 64.5±8.5 years vs 63.2±8.5 years), more likely male (73% vs 64.4%), and more frequently had preexisting CVD (79% vs 60.3%). These patients also more likely had a previous MI (38.6% vs 22.7%) or peripheral arterial disease (27% vs 21.5%) and presented with a higher mean systolic blood pressure (140.5±17.9 mm Hg vs 137.5±15.7 mm Hg) and lower estimated glomerular filtration rate (66.4±21.2 mL/min/1.73 m2 vs 70.5±22 mL/min/1.73 m2).

There was no benefit with canagliflozin relative to placebo with regard to the time to first MI event (hazard ratio [HR] 0.89 [95% CI, 0.75-1.05]). Treatment with canagliflozin was associated with reduced risk for non-STEMI (HR 0.78 [95% CI, 0.65-0.95]) but an increase in STEMI (HR 1.55 [95% CI, 1.06-2.27]).

There was no difference in the risk for type 1 or type 2 MI with treatment nor was there a change in the risk for fatal MI (HR 1.22 [95% CI, 0.78-1.93]).

Limitations of this study included its retrospective, post hoc nature as well as the researchers’ inability to classify some of the MI events.

The investigators wrote in their conclusion that “the potential directionally different effect of canagliflozin on STEMI and non-STEMI” found “in the CANVAS Program, but not confirmed in CREDENCE trial, warrants further investigation.”

Disclosure: This clinical trial was supported by Janssen Pharmaceuticals, Inc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Yu J, Li J, Leaver PJ, et al. Effects of canagliflozin on myocardial infarction: a post hoc analysis of the CANVAS Program and CREDENCE trial. Cardiovasc Res. Published online April 7, 2021. doi:10.1093/cvr/cvab128