Long-Term Survival Following Multivessel Revascularization in Patients With Diabetes: The FREEDOM Follow-On Study

Abstract

Background: The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial demonstrated that for patients with diabetes mellitus (DM) and multivessel coronary disease (MVD), coronary artery bypass grafting (CABG) is superior to percutaneous coronary intervention with drug-eluting stents (PCI-DES) in reducing the rate of major adverse cardiovascular and cerebrovascular events after a median follow-up of 3.8 years. It is not known, however, whether CABG confers a survival benefit after an extended follow-up period.

Objectives: The purpose of this study was to evaluate the long-term survival of DM patients with MVD undergoing coronary revascularization in the FREEDOM trial.

Methods: The FREEDOM trial randomized 1,900 patients with DM and MVD to undergo either PCI with sirolimus-eluting or paclitaxel-eluting stents or CABG on a background of optimal medical therapy. After completion of the trial, enrolling centers and patients were invited to participate in the FREEDOM Follow-On study. Survival was evaluated using Kaplan-Meier analysis, and Cox proportional hazards models were used for subgroup and multivariate analyses.

Results: A total of 25 centers (of 140 original centers) agreed to participate in the FREEDOM Follow-On study and contributed a total of 943 patients (49.6% of the original cohort) with a median follow-up of 7.5 years (range 0 to 13.2 years). Of the 1,900 patients, there were 314 deaths during the entire follow-up period (204 deaths in the original trial and 110 deaths in the FREEDOM Follow-On). The all-cause mortality rate was significantly higher in the PCI-DES group than in the CABG group (24.3% [159 deaths] vs. 18.3% [112 deaths]; hazard ratio: 1.36; 95% confidence interval: 1.07 to 1.74; p = 0.01). Of the 943 patients with extended follow-up, the all-cause mortality rate was 23.7% (99 deaths) in the PCI-DES group and 18.7% (72 deaths) in the CABG group (hazard ratio: 1.32; 95% confidence interval: 0.97 to 1.78; p = 0.076).

Conclusions: In patients with DM and MVD, coronary revascularization with CABG leads to lower all-cause mortality than with PCI-DES in long-term follow-up. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).

Keywords: coronary artery disease; coronary revascularization; diabetes.

Copyright © 2019. Published by Elsevier Inc.

Figures

FIGURE 1. Patient Flow in the Original FREEDOM Trial and the FREEDOM Follow-On Study

After the completion of the initial FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial, centers and patients were invited to participate in the FREEDOM Follow-On study. A total of 25 centers agreed to participate, resulting in a population of 943 patients. Excluding patients who died (n = 104), withdrew consent, or were lost to follow-up (n = 66) during the original FREEDOM follow-up, 773 patients were available to be followed. In the end, follow-up information was obtained for 766 patients (99% of the patients in the FREEDOM Follow-On). The expression “early terminate” in the bottom boxes refers to subjects who were lost to follow-up or withdrew consent before the beginning of the FREEDOM Follow-On study. As observed in the figure, there were numerical differences in the numbers of early termination and missing death status between the 2 treatment groups. CABG = coronary artery bypass grafting; PCI = percutaneous coronary intervention.

FIGURE 2. Kaplan-Meier Estimates of Survival in the 2 Treatment Groups

(A) Survival curves for the whole cohort with all patients enrolled in the FREEDOM trial, according to treatment group (n = 1,900). (B) Survival curves only for patients from the extended follow-up cohort, according to treatment group (n = 943). CI = confidence interval; HR = hazard ratio; other abbreviations as in Figure 1.

FIGURE 3. Subgroup Analysis of All-Cause Mortality for the Whole Cohort

The treatment effect compared PCI with drug-eluting stents versus CABG, both on top of optimal medical therapy. HRs for LVEF

CENTRAL ILLUSTRATION. Survival Curves According to the Revascularization Strategy in the FREEDOM Follow-On Study

KapLan-Meier estimates and survival curves including all patients enrolled in the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial (whole cohort of patients). Coronary artery bypass grafting results in a Long-term survival benefit in patients with diabetes and multivessel coronary disease when compared with revascularization with percutaneous coronary intervention with drug-eluting stents.