CHICAGO — The final long-term follow-up report from the landmark FREEDOM trial confirms that patients with diabetes who have multivessel CAD live longer with CABG than with PCI with drug-eluting stents, according to a presentation at the American Heart Association Scientific Sessions.
The FREEDOM Follow-On study, which extended follow-up of 943 patients from the original FREEDOM trial to a mean of 7.5 years, showed a greater reduction in all-cause mortality and a greater probability of survival among those who underwent CABG vs. PCI (18.7% vs. 23.7%; HR = 1.32; 95% CI, 0.97-1.78), Valentin Fuster, MD, PhD, MACC, director of Mount Sinai Heart and physician-in-chief of The Mount Sinai Hospital, said during the presentation.
All-cause mortality for the entire cohort, including patients followed for 3.8 years in the original trial and those followed for longer in FREEDOM Follow-On, was also lower with CABG vs. PCI (18.3% vs. 24.3%; HR = 1.36; 95% CI, 1.07-1.74).
In the extended follow-up cohort, the survival benefit of CABG was greatest in patients aged younger than 65 years at the time of randomization and there was a trend toward favoring CABG across subgroups, Fuster noted.
“In patients with diabetes and advanced CAD, CABG remains superior to PCI with DES in reducing all-cause mortality at a follow-up of 8 years,” Fuster said during the presentation. “These data support current recommendations that CABG be considered the preferred strategy for patients with diabetes and multivessel disease.”
The results from the original FREEDOM trial, published in The New England Journal of Medicine in 2012 and presented by Fuster at that year’s AHA Scientific Sessions, demonstrated that CABG, compared with PCI, led to a significant reduction in the composite of all-cause mortality, MI and stroke at a median of 3.8 years when compared with PCI with sirolimus- or paclitaxel-eluting stents in this patient population (18.7% vs. 26.6%; P = .005).
A reduction in all-cause mortality was also seen in the CABG group in the original trial, although this finding took a back seat in light of the other results, according to Fuster.
“Mortality was 16.3% in the PCI group and 10.9% in the CABG group, with a P value of .049,” he said. “We didn’t make a big issue of this at the time; we concentrated more on the overall result.”
During his talk, Fuster revisited his discussion of the original FREEDOM trial’s limitations from his first presentation in of the data in 2012, during which he noted that, for a long-term disease, 3.8 years of follow-up amounted to a relatively short-term study. He pointed out, though, that follow-up beyond 5 years after coronary revascularization trials is unusual due to a lack of funding and logistical obstacles.
“The objective of the FREEDOM Follow-On study was to examine long-term all-cause mortality in patients with diabetes and multivessel disease enrolled in the original FREEDOM trial,” he said.
Twenty-five centers with 943 patients, representing 49.6% of the 1,900 patients from the original cohort, agreed to participate in FREEDOM Follow-On.
“It’s a critically important point to note that, while it’s 50% of the original cohort, [the other 50%] are not patients whom we lost. Rather, these are 25 institutions that committed themselves to having outpatients be followed in a randomized fashion,” he said.
Although FREEDOM Follow-On was designed to address the limitation of the shorter-term follow-up in the original trial, this extended study was not without limitations, Fuster noted.
“Newer-generation stents were developed after the FREEDOM trial,” he said. “However, the results of FREEDOM must be interpreted based on the totality of the evidence demonstrating that changes in PCI platforms have not significantly altered the effect size of the long-term survival advantage of CABG over PCI.”
Fuster also pointed out that data about additional revascularization or other endpoints, including MI and stroke, were not included in the analysis of FREEDOM Follow-On.
Confirmation of current practice
Alice K. Jacobs
There are a number of issues that should be considered when evaluating or analyzing the quality of a randomized clinical trial, said Alice K. Jacobs, MD, from Boston University School of Medicine and Boston Medical Center. For instance, one should take into account whether the question is important and new, the design, sample size, endpoints, conclusions and applicability.
“In FREEDOM, the question is certainly important, although not new,” she said during a discussion of the FREEDOM Follow-On results.
She also noted there is possibility for bias in the design, as only about half the original cohort participated in the extended follow-up study. However, this is mitigated by several factors, including that the follow-up involved centers, not patients, according to Jacobs.
In terms of sample size, Jacobs said, the study may be underpowered, but again, this potential limitation is mitigated by the fact that the data from FREEDOM Follow-On participants were consistent with the overall cohort.
Importantly, she added, the FREEDOM results are applicable and support current clinical practice.
“The long-term results of FREEDOM add to the consistent evidence base supporting CABG as the preferred strategy for patients with diabetes and multivessel CAD,” Jacobs said. “Whether the continual evolution of new DES technology will diminish the advantage of CABG is unclear but appears less likely if the success of CABG is primarily due to protection of the myocardium against new disease. The contribution of additional procedures and other adverse outcomes during long-term follow-up, incomplete revascularization and importantly, newer medications for diabetes that improve cardiovascular outcomes will need to be considered to determine the optimal management of patients with diabetes and multivessel CAD.” – by Melissa Foster
Fuster V, et al. LBS.06 – Late Breaking Clinical Science in Coronary Revascularization. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.
Farkouh ME, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.11.001.
Disclosure: Fuster reports no relevant financial disclosures. Jacobs reports she has received research support from Abbott Vascular.