New Data Show COURAGE Findings Are Not Being Implemented

May 10, 2011

May 10, 2011 (Updated May 11, 2011) (New York, New York)— The percentage of patients with stable coronary artery disease receiving optimal medical therapy (OMT) did not noticeably improve following the landmark COURAGE trial in 2007, according to new data from a US PCI registry [1].

COURAGE found that OMT was just as good at preventing future events as receiving a stent on top of OMT in this patient population, and other studies have shown that rates of PCI have declined slightly among patients with stable disease, suggesting that more physicians may be appropriately treating patients with OMT instead of PCI.

But the new survey--covering almost 500 000 patients from >1000 hospitals in the ACC National Cardiovascular Data Registry (NCDR)--shows that, at least among patients ultimately treated with PCI, there was little change in prescribing practice from pre- to post-COURAGE. The findings illustrate the difficulty of translating the results of randomized clinical trials into mainstream clinical practice, say Dr William B Borden (Cornell University, New York, NY) and colleagues in their paper in the May 11, 2011 issue of the Journal of the American Medical Association.

Borden told heartwire he was "surprised" by the results from the registry. "I remember when the COURAGE trial was presented at ACC 2007, and reading it and seeing the publicity regarding the trial, both in the medical and public press, so I would have expected that we would have seen a more significant increase in applying medical therapy in this study."

There is this 'phase lag'--an educational gap--between the results of a randomized trial and them being incorporated into clinical practice.

But the lead author of COURAGE, Dr William E Boden (Buffalo General Hospital, NY), says he is not really surprised by the registry data. "This is consistent with other observations that have been made previously for years, that there is this 'phase lag'--an educational gap--between the results of a randomized trial and them being incorporated into clinical practice," he told heartwire . Boden is disappointed, however, that new US guidelines for stable CAD have not yet been issued, and he feels that these would have helped in the wider dissemination of the COURAGE results.

Interventional cardiologist Dr Tony Gershlick (University Hospitals Leicester, UK) told heartwire that the new study "is a really good, important paper because it reminds us about the importance of 'appropriate' medical therapy both before and after angioplasty, albeit a registry and prone to uncertainty about the robustness of the findings." However, he adds, "Notice I said 'appropriate,' rather than 'optimal,' because so-called trial-based optimal medical therapy may not always be a possibility; it can be sometimes hard in real life to institute the sort of medical therapy you seen in trials--not least, patients may have side effects from medication. It may also not be appropriate to continue with all medications postintervention. If a stable CAD patient has a PCI and is getting side effects from beta blockers, it's appropriate to stop them. So it might appear that medication is not 'optimal,' but it's appropriate." And furthermore, "There is OMT for symptoms vs OMT for prognosis," and it's important to differentiate between the two, he says.

More Contemporary Data Might Have Shown Some Difference

Boden also suggests that had this registry been a little more up-to-date--it ran through June 2009--the results might have been somewhat different, particularly as he believes interventionalists have only just recently stopped disputing the COURAGE results, which show that PCI can often be deferred in patients with stable CAD while OMT is given a chance to work.

"It's very likely or possible that, had the survey been more contemporary, we might have seen an increase in usage of OMT based on COURAGE and also BARI-2D, which replicated the findings of COURAGE and was published in 2009," he noted. "That said, it's still a little disappointing. One would expect that the use of medical therapy in this context would not be controversial, that we should use it in everybody regardless of whether or not they do or don't undergo PCI."

Responsible interventionalists have always undertaken intervention against a background of having tried to control symptoms first with OMT.

Gershlick agrees, with the caveat already noted that "appropriate" may sometimes be a better word to describe the medical therapy of choice. Having said that, he believes "responsible interventionalists have always undertaken intervention against a background of having tried to control symptoms first with OMT," he says.

Borden told heartwire he cannot speculate on what the results might have shown had they been more contemporary. But the data as they stand do have a number of important implications, say he and his colleagues, highlighting a continued opportunity to improve care among stable CAD patients. Much better communication between physicians of different specialties is required, they say, and doctors must take advantage of the "teachable moment" of an invasive procedure to impart to patients the importance of medical therapy. In addition, policymakers "will need to invest heavily in implementation research to facilitate the translation of evidence 'from bench to behavior,' " they observe.

Limited Effect of an Expensive, Highly Publicized Trial

In their paper, Borden et al explain that it has not been known to what degree OMT was being applied in routine practice in the stable CAD population or whether its use increased after COURAGE.

In their observational study, Borden and colleagues set out to examine the use of OMT in 467 211 patients with stable CAD undergoing elective PCI and in the NCDR before (September 1, 2005 to March 25, 2007) and after (July 1, 2007 to June 30, 2009) the publication of the COURAGE trial. Analysis compared use of OMT (defined as either being prescribed or having a documented contraindication to an antiplatelet agent, beta blocker, and statin) both before PCI and at the time of discharge.

Borden stressed to heartwire that although this was an observational study of those undergoing elective PCI, these were very much COURAGE-type patients: "We tried to match our patients to those in the COURAGE trial as best we were able to.

When we looked over time, and particularly with publication of the COURAGE results, it did not seem like these practice patterns changed to any meaningful degree.

"We found that less than half of people before PCI were taking OMT. Encouragingly, that did increase post-PCI to about two-thirds of patients being on OMT, but when we looked over time, and particularly with publication of the COURAGE results, it did not seem like these practice patterns changed to any meaningful degree," Borden told heartwire .

Specifically, before COURAGE, OMT was used in 43.5% of patients prior to PCI, and this increased to only 44.7% in the period after COURAGE (p<0.001). The use of OMT at discharge following PCI was 63.5% before COURAGE and 66.0% afterward (p<0.001).

Although the results are statistically significant because of the thousands of patients included, they are "not clinically significant," says Borden, representing just a net benefit of 1.2% increase in use of OMT before a stent was inserted and 2.5% afterward.

"These findings suggest a significant opportunity for improvement and a limited effect of an expensive, highly publicized trial on routine clinical practice," he and his colleagues observe.

Guidelines Are Key, Says COURAGE Author

Boden points out that research such as the COURAGE study always takes time to trickle down to the hospital floor for a number of reasons. "I don't think it's outside what we have observed previously. For example in acute coronary syndrome [ACS], it took several years before the results of CURE and CREDO became incorporated into practice and before the guidelines became widely disseminated and physicians began to use drugs like clopidogrel more widely."

We, as a cardiology community, have to do a much better job of educating the noncardiologists.

And he points out that the BARI-2D results strengthened the recommendations of COURAGE. "Many people may see one trial and say 'Oh well, one trial doesn't necessarily indicate that there is unanimity in terms of practice.' " But two trials puts a whole different spin on things, he stresses.

Boden does agree with the conclusions made by Borden et al that doctors need to collaborate more. "We, as a cardiology community, have to do a much better job of educating the noncardiologists to take care of these patients, such as the internist or the family practitioner."

And new guidelines would help tremendously in this aim, as well as in getting the message across to administrators, he notes. "Guidelines carry great weight with professional societies. If they were published and hopefully support the benefit of OMT, then cardiologists can approach physicians from other specialties. We have to do a better job in terms of promoting continuity of care--there has to be good communication between the specialist and the generalist. And it's certainly easier to be able to recommend a certain approach to management that has the support and clout of the guidelines."

Thus, he is eagerly awaiting the new recommendations on stable CAD "in which presumably the results of COURAGE will have an impact." These guidelines were "last published in 2002," he stresses, noting that he was one of several external reviewers who looked at a proposed draft of the new document back in January 2010, "and now it's more than a year later. It's disappointing that we have been awaiting these guidelines for two or three years and they haven't yet materialized."

But, he acknowledges, "Writing guidelines is never easy because it has to be done by a committee, and I suspect that there is probably a lot of disagreement among committee members, and that's an iterative process that takes time."

Interventionalists Begin to Accept COURAGE Data

Boden is encouraged, however, by the attitude of interventionalists, who, he believes, have really come around to the COURAGE results in the past year or two.

"Within the last one to two years, there's clearly been a shift in the thinking of the interventional cardiologist," he told heartwire . "They are no longer disputing or trying to denigrate the results of COURAGE. They have come to accept the importance of medical therapy, and they have come to understand that coronary heart disease is a systemic disease and that we need to treat all those risk factors and get them under control in addition to using PCI where it is indicated."

Gershlick disputes this somewhat, with his belief that "responsible" interventionalists have always recognized the importance of  appropriate medical therapy "The downside of COURAGE is that it may lead to patients not getting appropriate invasive investigation and important intervention, and that's not a good thing. I feel quite strongly about that."

He also stresses that "COURAGE said nothing about not doing coronary angiography. It's important to ensure that you don't have patients out there with residual, perhaps silent ischemia and critical stenoses. Those on significant amounts of medication required to control the symptoms should undergo angiography." And one should also ensure that patients who are on maximal medical therapy really are asymptomatic, he observes. 

"People underestimate how unpleasant angina is," he adds. "If one persists with a policy of medical management only, patients may still be getting angina symptoms, which will affect their quality of life, and angioplasty will improve it." In addition, many people simply do not want to take multiple medications long term, he says.

Borden reports participating in a one-time advisory board meeting for Kowa Pharmaceuticals. Disclosures for the coauthors are listed in the paper. Boden reports receiving grant support from Abbott and consultant/speaker's bureau fees from Gilead, Sanofi-Aventis, and Abbott. Gershlick has previously disclosed serving as an advisor or consultant for Abbott, Cordis, Boston Scientific, and Eli Lilly. He has received grants for clinical research from Medtronic.

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