The COURAGE Patients Who Crossed Over: New Insights

Michael O'Riordan and Shelley Wood

July 15, 2013

KANSAS CITY, MO — Patients in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial who crossed over from optimal medical therapy (OMT) to revascularization within one year of randomization were more likely to have severe angina that significantly affected quality of life and were more likely to be dissatisfied with their current treatment and healthcare system in which they were treated, according to a new analysis published online July 9, 2013 in Circulation: Cardiovascular Quality and Outcomes[1].

Importantly, crossing over from OMT to coronary revascularization was not associated with an increased risk of death or MI when compared with patients who underwent up-front revascularization, although angina and quality of life were typically worse (and worsened) in the OMT group in that first year.

Having that information, lead author Dr John Spertus (Mid America Heart Institute, Kansas City, MO) told heartwire , can now help doctors identify patients early on in whom PCI could be the initial therapy, something interventionalists have argued is needed in certain patients. But the analysis also provides the strongest argument to date that starting a COURAGE patient on medical therapy is reasonable and has no downside--something the COURAGE defenders have always insisted on.

"I think this is really the critical article about COURAGE, because it really addresses what many people were critical of with the trial, and that was that you saw these similar results [in the OMT and PCI-treated patients]. And people said that the reason you didn't see a difference in mortality or nonfatal MI was because the trial allowed these crossovers."

Critics of COURAGE point to the fact that "a third of patients crossed over," he continued. "But if you think of it clinically, the really critical crossovers are the crossovers in the first year." Those are the patients who truly can't be treated medically, as opposed to patients who went on to develop more progressive disease or additional disease. And in fact, of the 1168 patients randomized to OMT, only 16% of patients crossed over in the first year.

"So one in eight tried medical therapy and it just didn't work, so how are they different from everyone else?"

Of the 16% of patients who crossed over from OMT, 90% underwent PCI and 10% were treated surgically.

As noted, the most important predictors of early revascularization were the health status of patients at baseline and the healthcare system they were treated in. Patients with frequent and severe angina were more likely to cross over to revascularization, as were those dissatisfied with their treatment. In addition, compared with patients treated in the Veterans Affairs (VA) healthcare system, those treated in Canada were 37% more likely to undergo early revascularization. Patients treated at non-VA healthcare systems were 82% more likely to cross over to coronary revascularization in COURAGE.

This issue of "dissatisfaction" is nuanced, Spertus explained. Given that non-VA, non-Canadian hospitals were the ones where patients claimed to be the most dissatisfied, Spertus thinks these location data are likely a marker for hospitals where physicians were "already committed to angioplasty," which had been the standard of care prior to the COURAGE trial. "This is not a patient reason, this is a doctor reason," he said.

Importantly, in a comparison of matched patients who crossed over in the first year with patients randomized to up-front PCI, there was no difference in the rate of mortality or nonfatal MI. Health status, a measure of symptoms, function, and quality of life were not significantly different between these two groups at one-year follow-up.

"We did find, however, that compared with a matched group of patients treated with initial PCI, those who required early revascularization had a trend for more frequent admissions for unstable angina and suffered significantly worse angina and quality of life during the first year of follow-up," the authors write.

To heartwire , Spertus stressed that the analysis was not powered to say anything definite about the one-year crossover group, but no survival or MI differences were seen. "These are really the first data to show that these patients weren't harmed by being randomized to OMT, even though they crossed over in the first year."

And while patients did have worse symptoms during the first year of the trial, Spertus emphasized a point that he thinks is often lost on those who have debated these trial results over the past six years.

"This was not a randomized trial of drugs or devices, this was a randomized trial of processes of care." Going forward, patients with debilitating angina are a group in whom angioplasty may be the preferable therapy--something doctors on both sides of this debate may have already agreed upon. As for gauging "dissatisfaction" in order to determine the best treatment, Spertus points out that this is not necessarily something that is regularly considered. "Doctors don't often ask people that question: how dissatisfied are you with your current treatment for your chest pain? I think that's common sense. If someone is really dissatisfied with how they are being treated, you should treat them differently."

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