乌鸦传媒

Even after 15 years there was no discernible difference in survival for stable ischemic heart disease patients who were treated with optimal medical therapy compared with those who were initially treated with stents -- either bare metal or first-generation drug-eluting stents, according to the COURAGE investigators.

Extended survival information was available for 1,211, a little more than half of the original 2,287 patients who were randomized to optimal medical therapy alone or optimal medical therapy plus percutaneous coronary intervention (PCI), wrote , of the New York Veterans Affairs Healthcare Network, in the Nov. 12 issue of .

Patients in COURAGE were recruited from June 1999 through January 2004 and were randomly assigned, 1,249 to the PCI arm and 1,138 to the medical control group. In the PCI arm, 613 patients agreed to the use of their Social Security numbers for extended follow-up, as did 598 patients from the control group.

During the original study period, 54 patients in the stent group and 71 in the control group died.

The median duration of follow-up for sites that "permitted survival tracking" was 11.9 years and the overall median follow-up was 6.2 years.

A total of 561 deaths occurred over 15 years -- 284 in the stent group and 277 in the medical therapy arm.

Asked to comment on the findings, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic Foundation, pointed out that there were many limitations. "The authors were able to ascertain only one outcome, all-cause mortality, and were able to include only about half of the originally randomized patients. In long-term follow up, other non-cardiovascular causes of mortality may have a major impact. Nonetheless, there appears to be no clear advantage to PCI over medical therapy in this analysis."

"After COURAGE was reported, a lot of people were digging in sub-groups to try to identify a group that would really benefit from PCI," former American College of Cardiology president , of Brigham and Women's Hospital in Boston, told 乌鸦传媒.

Sedlis and colleagues acknowledged that data mining effort, noting that both prespecified and post hoc analyses of the COURAGE data failed to define a specific subgroup that would have initial benefit.

O'Gara said that the intervening years have seen a shift away from what many consider inappropriate stenting to more appropriate and considered use of PCI. That move has been greatly aided by the development of fractional-flow reserve technology that allows operators to know the precise rate of flow within arteries, thus clarifying the decision to stent or not.

When the COURAGE results were initially reported at the American College of Cardiology meeting in 2007, it was the height of turf wars among those who treat coronary artery disease: medical cardiologists versus interventional cardiologists, and interventional cardiologists versus cardiovascular surgeons.

Thus the finding that stenting was no better than optimal medical therapy was considered a "win" for the non-interventional community, and the surgeons could take solace from the fact that COURAGE was not considered a "win" for interventional cardiology.

At the outset many interventional cardiologists criticized the trial saying it selected the wrong patients and used the wrong devices -- and in fact stent platforms had evolved rapidly from 1999 to 2004.

Many interventionalists expressed the belief that time would prove PCI superior. In fact, "the survival curves appeared to separate at 5 years in favor of PCI (hazard ratio for death 0.87, 95% CI 0.65-1.13)," Sedlis and colleagues wrote, "which suggested that a late survival benefit with an initial strategy of PCI may have emerged toward the end of the follow-up period. However, after 15 years of extended follow-up, nearly half the VA patients and one quarter of the non-VA patients in the study had died, and no late trend emerged to suggest a survival benefit with initial PCI."

Looking back from the distance of almost 9 years, it is difficult to appreciate controversy that surrounded COURAGE, which included a spectacular embargo break that resulted in the censure of Martin Leon, MD, of Columbia University. Leon, who was one of NEJM's peer reviewers, spilled the results at an industry-sponsored symposium more than 24 hours before they were scheduled for presentation and a writer for Wall Street Journal's website ran with the story. NEJM banned Leon from participating as a reviewer or writing perspectives for 5 years and the ACC sanctioned him by barring him from participating in the ACC 2008 meeting.

There were no long-term sequelae for Leon, though, and he was back in the spotlight at the ACC in 2011 when he was part of the team that reported results from the PARTNER trial, which found transcatheter aortic valve implantation as good as surgery for treating high-risk patients with aortic stenosis.

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