Insulin Use Linked to Risk for MACE Among Individuals With Stable Diabetes and Acute Coronary Syndrome

Insulin injection
Investigators evaluated data from BETonMACE to assess a relationship between the use of insulin and risk of MACE in patients with diabetes and acute coronary syndrome.

Individuals with acute coronary syndrome (ACS) and stable type 2 diabetes (T2D) who use insulin may be at increased risk for major adverse cardiovascular events (MACE) despite the use of proven therapies. These findings, according to an analysis of data from a phase 3 trial, were published in Cardiovascular Diabetology.

The phase 3 trial BETonMACE ( Identifier: NCT02586155) recruited patients with ACS, low high-density lipoprotein cholesterol (HDL-C), and T2D. In this analysis, patients (N=2418) were randomly assigned to receive apabetalone or placebo, and the incidence of MACE (cardiovascular death, myocardial infarction, or stroke) among subgroups of patients was assessed.

The median age of patients was 61.3 years (standard deviation [SD], 9.5), 25.6% of whom were women, and 12.4% were non-White. Stratified by insulin use, individuals who used insulin (n=829) differed significantly by baseline characteristics including gender, ethnicity, duration of diabetes, medication use, prior cardiovascular events, and glycemic control.

Among the placebo cohort, individuals treated with insulin were at increased risk for MACE (adjusted hazard ratio [aHR], 2.10; 95% CI, 1.42-3.10; P =.0002) and for hospitalization for heart failure (aHR, 2.34; 95% CI, 1.19-4.60; P =.01) at 3 years.

The interaction between insulin and apabetalone was not significant (P =.078), in which the MACE risk difference on the basis of apabetalone therapy among the insulin-treated (aHR, 0.80; 95% CI, 0.57-1.14; P =.23) and noninsulin-treated (aHR, 0.85; 95% CI, 0.61-1.18; P =.42) populations was not significant.

Treatment-emergent adverse events were more frequently observed among patients who used insulin (79% vs 62%), particularly for cardiovascular (28% vs 20%) and hematologic (7% vs 3%) events.

This study was limited by the lack of data about insulin use during hospitalization for ACS and associated revascularization procedures. The investigators were also unable to assess to which extent the low HDL-C inclusion criteria influenced the observed outcomes. It remains unclear whether these findings could be generalizable to a similar population of patients with normal HDL-C.

These data, therefore, indicate an association between insulin use and increased risk for MACE and heart failure hospitalization among patients with T2D and ACS comorbidities.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Schwartz GG, Nicholls SJ, Toth PP, et al. Relation of insulin treatment for type 2 diabetes to the risk of major adverse cardiovascular events after acute coronary syndrome: an analysis of the BETonMACE randomized clinical trial. Cardiovasc Diabetol. 2021;20(1):125. doi:10.1186/s12933-021-01311-9