乌鸦传媒

SAN FRANCISCO, July 15 -- Endoscopic harvesting of veins for coronary artery bypass graft (CABG) surgery may compromise long-term outcomes, researchers found.

Compared with open surgery to harvest grafts, endoscopic procedures had higher 12- to 18-month vein-graft failure (46.7% versus 38.0%, P<0.001), John H. Alexander, MD, of Duke University Medical Center, and colleagues reported.

Moreover, endoscopic harvesting was associated with significantly higher mortality, MI, and repeat revascularization rates at three years, they wrote in the July 16 issue of the New England Journal of Medicine.

"Open harvesting, though more invasive and associated with more wound complications, may be less traumatic to the vein and could result in a better conduit," they suggested.

While this explanation is speculation, it makes sense mechanistically, Dr. Alexander said. "If you've ever seen one of these procedures, there's clearly more tugging on the vein and more rough handling of the vein when it's harvested endoscopically."

Minimally invasive methods have largely become standard of care because of advantages such as less pain, shorter hospital stays, and substantially smaller scars.

However, the studies that produced this evidence had short-term follow-up, were not randomized, or did not evaluate clinically important outcomes, leaving little known about long-term effects.

This may explain the difference in findings, because the separation in outcomes in Dr. Alexander's analysis did not become apparent until almost one year after CABG.

Dr. Alexander cautioned against a dramatic shift in practice back to open harvesting, stressing instead the need to discuss these potential long-term risks with patients.

Likewise, Timothy Gardner, MD, president of the American Heart Association, wasn't ready to abandon endoscopic methods on the basis of this one study, though agreeing that more care is warranted.

"I'm sure that surgeons that use this technique will be much more careful, will take extra steps to avoid trauma to the vein while it's being harvested," he said, "and will probably be more inclined to add an extra incision if they find themselves in a situation where it's hard to get the vein out."

The focus should be on ways to improve endoscopic vein harvesting techniques "to reduce the trauma associated with it and allow patients to get both the short-term benefits and avoid the long-term risks," Dr. Alexander said.

And since patients in the trial their analysis was based on had not been randomly assigned to vein harvesting method, randomized clinical trials with long-term follow-up of clinically relevant outcomes are now needed to settle the issue, Dr. Alexander's group emphasized.

The analysis included 1,753 CABG patients who had endoscopic harvesting and 1,247 who had graft harvesting under direct vision as part of the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV trial.

Primary outcomes of that phase III placebo-controlled trial showed no benefit to ex vivo treatment of vein grafts with the investigational "DNA decoy" edifoligide meant to reduce graft failure. (See AHA: Gene Therapy Fails to Prevent Saphenous Vein Graft Failure)

The treating surgeon determined the method of graft harvesting, but secondary-prevention medication use was largely similar between groups.

Through three years of follow-up, endoscopic harvesting was associated with:

• A higher composite rate of death, MI, or revascularization (20.2% versus 17.4%, adjusted hazard ratio 1.22, 95% CI 1.01 to 1.47, P=0.04)
• A higher rate of death or MI (9.3% versus 7.6%, adjusted HR 1.38, 95% CI 1.07 to 1.77, P=0.01)
• Higher mortality rates (7.4% versus 5.8%, adjusted HR 1.52, 95% CI 1.13 to 2.04, P=0.005)

Treatment with edifoligide did not interact with type of vein-graft harvesting for any of these outcomes; nor did a sensitivity analysis controlling for differences between groups in a propensity score eliminate the associations.

Endoscopic harvesting also remained significantly associated with higher rates of vein-graft failure (adjusted odds ratio 1.35, 95% CI 1.15 to 1.60, P<0.001) after adjustment for the propensity score.

The researchers cautioned, though, that unmeasured confounders in physician selection of patients for endoscopic versus open harvesting may have contributed to the results.

Notably, the study did not control for the type of endoscopic vein harvesting device used because these data were not collected.

The PREVENT IV trial, on which this study was based, was funded by a grant from Corgentech (now Anesiva). Dr. Alexander reported conflicts of interest with AstraZeneca, Bristol Myers Squibb, Medtronic Japan, the National Institutes of Health, Portola Pharmaceuticals, and Regado Biosciences. Co-authors reported conflicts of interest with MAQUET, Bristol Myers Squibb, Centocor, Eli Lilly & Co., Merck, Pfizer, sanofi-aventis, Saint Jude's, the American Heart Association, the American College of Cardiology, the Society of Thoracic Surgeons, Abbott Laboratories, Abbott Vascular Business, Abiomed, Acorn Cardiovascular, Actelion, Annenberg, Heart.org, Kowa Research Institute, NITROX, Novartis Pharmaceutical, and Schering Plough. Dr. Gardner reported no conflicts of interest.

Comment