Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus

David D Berg; Filipe A Moura; Andrea Bellavia; Benjamin M Scirica; Stephen D Wiviott; Deepak L Bhatt; Itamar Raz; Erin A Bohula; Robert P Giugliano; Jeong-Gun Park; Mark W Feinberg; Eugene Braunwald; David A Morrow; Marc S Sabatine

doi:10.1016/j.jacc.2023.04.031

Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus

J Am Coll Cardiol. 2023 Jun 27;81(25):2391-2402. doi: 10.1016/j.jacc.2023.04.031.

Affiliations

¹ TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: dberg1@bwh.harvard.edu.
² TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, New York, USA.
⁴ Faculty of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
⁵ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 37344040
DOI: 10.1016/j.jacc.2023.04.031

Abstract

Background: Risk of atherothrombotic events is not uniform in patients with type 2 diabetes mellitus (T2DM). Tailored risk assessment may help guide selection of pharmacotherapies for cardiovascular primary and secondary prevention.

Objectives: The purpose of this study was to develop a risk model for atherothrombosis in patients with T2DM.

Methods: We developed and validated a risk model for myocardial infarction (MI) or ischemic stroke (IS) in a pooled cohort of 42,181 patients with T2DM from 4 TIMI (Thrombolysis In Myocardial Infarction) clinical trial cohorts. Candidate variables were assessed with multivariable Cox regression, and independent variables (P < 0.05) were retained in the final model. Discrimination and calibration were assessed. Treatment interactions with dapagliflozin (sodium-glucose cotransporter-2 inhibitor) and evolocumab (proprotein convertase subtilisin/kexin type 9 inhibitor) were explored in the DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis In Myocardial Infarction 58) and FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trials, respectively.

Results: Sixteen variables were independent predictors of MI or IS. The model identified a >8-fold gradient of MI or IS rates between the top vs bottom risk quintiles in the validation cohort (3-year Kaplan-Meier rate: 14.9% vs 1.4%; P < 0.0001). C-indexes were 0.704 and 0.706 in the derivation and validation cohorts, respectively. The model was well-calibrated in both primary and secondary prevention. Absolute reduction in the rates of MI or IS tended to be greater in patients with higher baseline predicted risk for both dapagliflozin (absolute risk reduction: 2.1% vs 0.2%) and evolocumab (absolute risk reduction: 3.2% vs 1.0%).

Conclusions: We developed and validated a risk score for atherothrombotic events, leveraging 16 routinely assessed clinical variables in patients with T2DM. The score has the potential to improve risk assessment and inform clinical decision-making.

Keywords: atherothrombosis; clinical trials; diabetes mellitus; ischemic stroke; myocardial infarction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Diabetes Mellitus, Type 2* / epidemiology
Humans
Myocardial Infarction* / complications
Proprotein Convertase 9
Risk Assessment
Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

PCSK9 protein, human
dapagliflozin
Proprotein Convertase 9
Sodium-Glucose Transporter 2 Inhibitors