Even at 8 Years, CABG Bests PCI in Diabetes: FREEDOM Study Extended

November 28, 2018

CHICAGO — The well-recognized survival advantage of coronary bypass surgery (CABG) over stenting in diabetic patients with multivessel coronary disease (MVD) persists for the better part of a decade, suggests an analysis of patients in the FREEDOM trial.

The guidelines already strongly prefer CABG over percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in such patients, based partly on FREEDOM, but survival data as late as the median 7.5 years of the current analysis are rare.

Also noteworthy in the new study, the superior late survival after CABG compared with PCI seemed especially pronounced in patients younger than 65 years and in any who had ever smoked. The two treatments fared similarly in older patients and never-smokers (interaction P values for age and smoking status, .001 and .01, respectively).

"Younger patients are those in whom we often defer CABG," many times preferring PCI so as to avoid or postpone cardiac surgery, Michael E. Farkouh, MD, MSc, University of Toronto, told theheart.org | Medscape Cardiology.

"But in fact what we found in FREEDOM was the benefit of CABG was largely conferred to those who were young — which we believe to be potentially practice-changing."

Farkouh is lead author on the extended follow-up analysis of FREEDOM, called FREEDOM Follow-on, published online November 11 in the Journal of the American College of Cardiology to coincide with its presentation at the American Heart Association (AHA) Scientific Sessions 2018.

The primary trial had randomized 1900 patients with diabetes and MVD to undergo either CABG, using a left-internal mammary artery as the primary graft, or PCI with a sirolimus or paclitaxel DES, both on top of optimal medication.

The rate of death, nonfatal myocardial infarction (MI), or nonfatal stroke, the primary end point, had been 26.6% in the PCI group and 18.7% in the CABG group (= .005) after a median of 3.8 years.

Importantly, patients in FREEDOM had been required to have MVD that did not include the left-anterior descending coronary artery, and PCI was performed with DES of the era; the study was first reported in 2012.

FREEDOM Follow-on continued tracking about half the original cohort for a median of 7.5 years (interquartile range, 5 to 9 years, and for as long as 13 years). The cohort consisted of the 49.6% of the main trial's patients who were treated at 25 of the original 140 study centers that had agreed to continued follow-up.

Although the remaining half of the primary FREEDOM cohort could not be followed further, the investigators included them in the late survival analysis using data up to their final follow-up in 2012.

That created both an overall cohort and a smaller extended-follow-up cohort, analyzed separately for late survival outcomes, which turned out very similar in the two cohorts.

Total Mortality (%) in Overall and Follow-up Cohorts by Type of Revascularization: FREEDOM Follow-on*
Population PCI, n (%) CABG, n (%)
Overall cohort 953 (24.3) 947 (18.3)
Extended-follow-up cohort 478 (23.7) 465 (18.7)
*Median follow-up, 7.5 years

In adjusted analysis, the difference was significant in the overall cohort, where the mortality hazard ratio (HR) for PCI vs CABG was 1.38 (95% CI, 1.08 - 1.76; P = .01). But it fell short of significance in the smaller extended-follow-up cohort: HR, 1.32 (95% CI, 0.97 - 1.79; P = .076).

In the overall cohort, survival curves for patients managed with CABG vs PCI started to separate early, and continued to separate consistently over time, Alice K. Jacobs, MD, Boston University School of Medicine, said in an interview with theheart.org | Medscape Cardiology.

"This trend was also observed in the extended-follow-up group," she said, resulting in similar mortality outcomes. Jacobs agreed with the report's authors that the difference did not reach significance "likely due to a lack of power" in the smaller cohort.

That limitation of the extended-follow-up cohort was "mitigated by the fact that the results were consistent with the overall trial cohort," Jacobs had said earlier as invited discussant after the live presentation of FREEDOM Follow-on at the AHA sessions.

The new analysis, with its long-term follow-up insights, "adds to the consistent evidence base supporting CABG as the preferred strategy for patients with diabetes and multivessel disease," she said.

She noted that advances in coronary stent technology since 2012 could potentially "diminish the advantage of CABG." But stent advances would be less likely to narrow the gap "if the success of CABG is primarily due to protection of the myocardium against new disease."

Farkouh reiterated that point, noting that both CABG and coronary stents have evolved in the intervening years, which have seen increasing use of arterial grafts in CABG matched with improvements in stent hardware, better antithrombotic therapy, and less stent thrombosis.

But such PCI gains with a short-term impact probably didn't much influence survival differences in the current analysis, he said. Mortality in a long-term study "is not procedural mortality. It's mortality due to how well the myocardium is revascularized, how well it's protected from future MI. It's a long-term issue, not a short-term issue."

Put another way, "Newer-generation stents were developed after the FREEDOM trial, but I don't know of any stent that is new, compared with the previous ones, that changes mortality by 6% in absolute value," said Valentin Fuster, MD, PhD, Icahn School of Medicine at Mount Sinai, New York City, when presenting the analysis at the AHA sessions. He is also senior author on the published report.

FREEDOM Follow-on was funded by the Joseph and Vicky Safra Foundation. The FREEDOM trial was funded by the National Heart, Lung and Blood Institute. Farkouh and Fuster had no relevant disclosures. Jacobs discloses receiving support for research from Abbott Vascular.

American Heart Association (AHA) Scientific Sessions 2018: Abstract 18609. Presented November 11, 2018.

J Am Coll Cardiol. Published online November 11, 2018. Report

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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