Insulin Increases Risk of Thromboembolic Events in Patients with Atrial Fibrillation

Insulin-required diabetes increases the risk of thromboembolic events in patients with atrial fibrillation (AF), according to a study published in theJournal of the American College of Cardiology.

Included in the European Prevention of Thromboembolic Events-European Registry in Atrial Fibrillation (PREFER AF) study were 5717 patients with AF from Austria, France, Germany, Italy, Spain, Switzerland, and the United States.

Of the 5717 patients, 1288 had diabetes, and 288 of the patients with diabetes were receiving insulin treatment.

Compared with patients without diabetes, those with diabetes had an increased prevalence of systemic hypertension, congestive heart failure, prior transient ischemic attack/stroke/thromboembolism, vascular disease, chronic renal impairment, left atrial enlargement, chronic obstructive pulmonary disease, and body mass index higher than 30 kg/m2; regardless of insulin status.

Those with insulin-required diabetes had a higher use of vitamin K antagonists plus antiplatelet therapy (16.7% vs 9.6%) at baseline and 1 year (71.5% vs 62.9%).

The primary endpoint of PREFER AF was stroke/systemic embolism incidence at 1-year follow-up according to diabetes status—–no diabetes, noninsulin-requiring diabetes, or insulin-requiring diabetes.

In the overall population, the results of the study showed that at 1 year the incidence of stroke/systemic embolism was 2 per 100 patients per year. Patients who required insulin was associated with a higher risk for the primary endpoint compared with no diabetes (5.2 per 100 patients per year versus 1.9 per 100 patients per year, respectively).

No differences in stroke/systemic embolism rates were found between insulin-requiring diabetes and no diabetes, according to the study. Patients who received insulin tended to have an increased prevalence of sustained AF (80%) compared with noninsulin-requiring diabetes (76%) and patients without diabetes (67%).

Even after the investigators added various risk factors as covariates to the Cox proportional hazard regression model, the correlation between insulin-requiring diabetes and higher rates of thromboembolic events remained significant.

In a comparison between insulin-requiring diabetes and noninsulin-requiring diabetes, 2 of 15 covariates had statistically significant interactions. Specifically, the relative increase of insulin-induced thromboembolic events was higher in patients with congestive heart failure, as well as in patients who were receiving antithrombotic therapy at baseline.

High rates of stroke/systemic embolism were still present in patients with insulin-requiring diabetes who received anticoagulation at baseline, according to the study. The daily dose of the patient’s insulin did not appear to affect thromboembolic risk, the authors noted.

Additionally, the rate of stroke/systemic embolism was 2.0% at 1 year in patients without diabetes or noninsulin-requiring diabetes with a CHA₂DS₂-VASc score [(Congestive heart failure, Hypertension, Age ( > 65 = 1 point, > 75 = 2 points), Diabetes, and Stroke/TIA (2 points)] higher than 1.

Limitations to the study were that investigators could not determine the thromboembolic risk of the untreated patients or the risk associated with specific antithrombotic therapies; residual confounding cannot be ruled out; the inability to stratify the thromboembolic risk for patients with diabetes who received insulin therapy according to the CHA₂DS₂-VASc scores due to the study size; a uniform definition may not have been used; and unavailable data on specific criteria for initiating insulin therapy or on glycemic control.

“The surprising finding of our study was the strikingly similar incidence of thromboembolic events at 1 year in patients with diabetes but without insulin treatment compared with patients without diabetes,” the authors wrote. “According to our data, it is the need for insulin therapy, rather than the presence of diabetes per se that seems to be an independent factor affecting the occurrence of AF-related stroke/systemic embolism during follow-up.”