FREEDOM: Insulin therapy increased CV risk after revascularization in diabetes

Issue: December 2013

SAN FRANCISCO — Patients with diabetes and CAD who are treated with insulin experienced more major adverse CV events after revascularization than those not receiving insulin therapy, according to a subanalysis of the FREEDOM trial.

Perspective from Spencer B. King III, MD

Michael E. Farkouh, MD, MSc, associate clinical professor of medicine at Mount Sinai School of Medicine, and colleagues evaluated 1,850 patients with diabetes and multivessel CAD to CABG (n=894) or PCI with a first-generation drug-eluting stent (DES; n=956). Of these patients, 602 patients were treated with insulin at baseline, including 325 in the PCI group and 277 in the CABG group. All participants had greater than 70% stenosis in more than two major vessels with no left main stenoses. The primary endpoint for the subanalysis was a composite of major adverse CV events, including death, MI or stroke.

The estimated percentage of major CV events at 5 years was 29% among insulin-treated patients compared with 19% among noninsulin-treated patients (P<.001). Regardless of insulin treatment status, the estimated percentage at 5 years remained elevated among those who underwent PCI (insulin, 32.2% and no insulin, 23.2%) vs. CABG (insulin, 24.3% and no insulin, 15.6%). However, stroke rates were higher among patients who underwent CABG (insulin, 7.5% and no insulin, 4.3% vs. PCI (insulin, 3.7% and no insulin, 1.7%). No significant interaction affecting the primary endpoint between insulin therapy and assigned CAD treatment was observed (P=.4)

The insulin-treated group included significantly fewer men compared with the noninsulin-treated group (61.3% vs. 76.5%; P<.0001); patients with higher BMI (30.5 vs. 29.3; P<.0001), a longer duration of diabetes (15.1 vs. 7.7 years; P<.0001) and higher HbA1c (8.5% vs. 7.5%; P<.0001). They were significantly more likely to have congestive HF (32.1% vs. 24.3%; P=.0004) and ACS (35.1% vs. 28.6%; P=.005).

“In patients with diabetes and multivessel disease in the FREEDOM trial, predominantly a 3-vessel coronary disease trial, there are more major adverse coronary events in patients treated with insulin than in those that are not, but the differences in clinical outcomes between CABG and PCI appear to be maintained [regardless of insulin treatment],” Farkouh said at a press conference.

For more information:

Dangas GD. Session XVI: First report investigations II. Presented at: TCT 2013; Oct. 27-Nov. 1, 2013, San Francisco.

Disclosure: Farkouh reports receiving grant/research support for the FREEDOM trial from Boston Scientific, Cordis, Eli Lilly and Sanofi.

Perspective

Spencer B. King III, MD

This further analysis of the FREEDOM trial did not show that patients who did not require insulin had a different outcome than the total group. The advantage of surgery in these diabetic patients was maintained in both the insulin-requiring patients and the patients who do not require insulin.

The final question that everyone asks about FREEDOM is, should all diabetic patients have surgery rather than interventions if they have multivessel disease? The answer to that is not contained in this substudy, nor in the total study, because it included very few patients with isolated lesions and a low SYNTAX score. We did not show that those are better with surgery. We just don’t have enough patients at the low end of the risk score to make that conclusion.

Spencer B. King III, MD

Cardiology Today Editorial Board member

Disclosures: King reports serving on the steering committee of the FREEDOM study and was a co-author of the paper reporting its main findings, but was not involved in the present subanalysis.