FREEDOM: Bypass Bests Stents for Diabetics

By Peggy Peck, Editor-in-Chief, MedPage Today

Published: November 04, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Bypass surgery is a better treatment choice than stenting for diabetics with multivessel coronary artery disease.
In a study of 1,900 patients, the 5-year rate of death, myocardial infarction, or stroke was 26.6% among patients who had arteries opened with stents versus 18.7% in the coronary artery bypass graft (CABG) group, which represented 200 events in the stent arm versus 146 in the surgery group (P=0.005), wrote Valentin Fuster, MD, PhD, of Mount Sinai School of Medicine in New York City, and colleagues in a study published online Nov. 4 by the New England Journal of Medicine.
The superiority of surgery was driven by more than a doubling in the 5-year MI rate in the stent arm -- 13.9% versus 6% (P<0 --="--" .001=".001" 10.9="10.9" 16.3="16.3" 5="5" a="a" and="and" at="at" lower="lower" mortality="mortality" rate="rate" versus="versus" years="years">P
=0.049). Moreover, surgery bested stents regardless of disease severity as measured by the SYNTAX score, beginning with a 6% benefit in composite endpoint favoring CABG for low-risk patients, 10% for moderate risk, and 8% for high-risk patients.
"This will absolutely change clinical practice because this is a big difference," Fuster told MedPage Today. In addition to the NEJM publication, the FREEDOM results were also reported at a late-breaking clinical trials session at the American Heart Association meeting in Los Angeles.
In an editorial that accompanied the study, Mark Hlatky, MD, of Stanford University in Palo Alto, Calif., echoed Fuster's assessment.
"As a cardiologist who does not perform either procedure, I find that the FREEDOM trial provides compelling evidence of the comparative effectiveness of CABG versus [percutaneous coronary intervention] in patients with diabetes and multivessel coronary artery disease," he wrote.
And the finding is hardly surprising since 17 years ago the National Heart, Lung, and Blood Institute warned cardiologists that patients who underwent bypass surgery had better survival rates than patients treated with PCI. Since that time, a number of studies, most notably SYNTAX, reached the same conclusion.
Yet, in the real world of clinical practice, "more patients with diabetes have undergone PCI rather than CABG to treat multivessel coronary disease," Hlatky wrote.
Asked to speculate why the use of PCI has continued to grow as demand for bypass surgery has declined in the face of evidence supporting the benefit of surgery, heart surgeon Timothy Gardner, MD, told MedPage Today, that patients, families, and cardiologists "don't like surgery because it is traumatic. It is traumatic at every level -- patient, family, and cardiologist."
As a result, he said, there is a "a grudging reluctance to accept evidence that favors CABG."
But Gardner, who is medical director of Christiana Care's Center for Heart and Cardiovascular Health in Newark, Del., and a former president of the AHA, said the evidence from FREEDOM should not be ignored.
"I think this is a class I, evidence level A, finding," he said.
Another reason for the apparent disconnect between evidence and practice may be stroke risk.
In CABG versus PCI trials, stroke rate is higher in the surgery arm and this again was the case in FREEDOM.
At the 5-year mark, the stroke rate was significantly higher in the surgery arm -- 5.2% versus 2.4% -- but the number of strokes was low in both arms -- 20 in the stent group and 37 in the surgery arm (P =0.03). However, this P-value was calculated as "P=0.16 by the Wald test of the Cox regression estimate for the study-group assignment in 1,712 patients after adjustment for the average glucose level after the procedure."
And although CABG was clearly superior on the primary endpoint at 5 years and at 2 years, at 30 days just 26 stent patients reached the composite endpoint versus 42 patients in the surgery arm.
The Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) study enrolled 1,900 patients over a 5-year period from 2005 through 2010. Most patients were in the early 60s (mean age 63) and most of the patients (83%) were men.
The mean SYNTAX score (a measure of disease complexity) was 26.2±8.6. Patients randomized to the PCI group who did receive interventional treatment were given either sirolimus-eluting stents (Cypher) or paclitaxel-eluting stents (Taxus).
The median follow-up for all patients was 3.8 years.
As might be expected, antiplatelet therapy was more common among patients in the stent group, but use of cardiovascular medications including statins, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, was the same in both groups.
Fuster and colleagues noted a number of limitations for the study including the unblinded design of the trial, which may have caused some surgical patients to "have been treated differently on the basis of their surgical procedure."
Another limitation, they wrote, was a lack of statistical power in some of the prespecified subgroups.

The FREEDOM trial was supported by grants from the National Heart, Lung, and Blood Institute. Cordis, Johnson & Johnson, and Boston Scientific provided the stents; Eli Lilly provided abciximab and an unrestricted research grant; sanofi aventis and Bristol-Myers Squibb provided clopidogrel.
Fuster reported a nonsignificant relationship with BG Medicine. Gardner had no relevant financial conflicts of interest.
Hlaky disclosed payments from the American College of Cardiology for work as an associate editor of the Journal of the American Medical Association, and as a consultant to Blue Cross Blue Shield Association, Partners Healthcare System, Kaiser Permanente of Northern California, Consumers Union, the Medicines Company, Gilead, Genentech, Altarum Institute, the National Heart, Lung, and Blood Institute, California Pacific Medical Center, and Up to Date.

From the American Heart Association:

Primary source: New England Journal of Medicine
Source reference:
Farkouh, ME et al "Strategies for mulitvessel revascularization in patients with diabetes" NEJM 2012; DOI: 10.1056/NEJMoa1211585.
Additional source: New England Journal of Medicine
Source reference:
Hlatky, MA et al "Compelling evidence for coronary-bypass surgery in patients with diabetes" NEJM 2012; DOI: 10.1056/NEJMe1212278.

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Peggy Peck
Vice President / Executive Editor
Peggy Peck began her career in journalism at The Record, a New Jersey daily newspaper. In 1980, she started writing for the medical trade press with a column in Physicianâ€™s Management. Since then, her byline has been ubiquitous, appearing in Modern Medicine, Medical Tribune, Medical World News, Physicianâ€™s Weekly, Internal Medicine News, Family Practice News, Pediatric News, Clinical Psychiatry News, Skin and Allergy News and ObGyn News. As a freelancer, she has contributed to WebMD, Medscape, Reuters Health, UPI, Oncology Times, Neurology Today, Neurology Now, and AMNews.

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