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DENVER -- Percutaneous coronary intervention (PCI) was no better than a sham procedure at providing relief to stable angina patients, the 200-person ORBITA trial showed.

At 6 weeks after having been randomized to drug-eluting stents (DES) or a sham procedure, patients had similar improvements in exercise time (28.4 more seconds with PCI versus 11.8 more seconds with placebo, P=0.200), according to the late-breaking trial presented at the Transcatheter Cardiovascular Therapeutics meeting here. ORBITA was simultaneously published online in .

The bulk of other endpoints yielded no differences between groups either, Justin Davies, of Imperial College London, MRCP, and colleagues reported:

• Time to 1 mm ST depression (472.7 versus 470.1 seconds, P=0.164)
• Change in peak oxygen uptake (-2.0 mL/min versus +10.9 mL/min, P=0.741)
• Change in Seattle Angina Questionnaire (SAQ) physical limitation score (+7.4 versus +5.0 points, P=0.420)
• Change in SAQ angina frequency (+14.0 versus +9.6 points, P=0.260)
• Change in SAQ angina stability (-4.2 versus -5.1 points, P=0.851)
• Quality of life on the 5-level version of the EuroQol 5 dimensions questionnaire (+0.03 for both, P=0.994)
• Duke treadmill score (+1.22 versus +0.10, P=0.104)

PCI's sole significant advantage was the greater improvement of a patient's dobutamine stress echocardiography (DSE) peak stress wall motion score index (-0.08 versus +0.02, P=0.0011).

"The results of ORBITA, the only blinded, randomised placebo-controlled trial of PCI, show that even with severe coronary stenosis, exercise capacity and symptoms are not improved significantly compared with a placebo intervention," Davies' group concluded. "[Forty] years after the first PCI, ORBITA's findings show that placebo-controlled randomised trials remain necessary."

The authors commented that "forgetting the potential magnitude of placebo effects prevents exploration of the inevitably complex relationship between anatomy, physiology, and symptoms. Clinicians have hoped there might be a simple entity named ischaemia, which manifests as positive tests and clinical symptoms, and that treatment by PCI would eliminate all these manifestations concordantly."

"Perhaps this notion is too optimistic," they continued, although emphasizing that ORBITA has no bearing on the treatment of acute coronary syndrome, for which PCI has been proven effective.

"Nevertheless the findings of ORBITA do not mean that patients should never undergo PCI for stable angina. Not all patients would be satisfied with taking multiple antianginal agents forever. They might prefer an invasive procedure with a small procedural risk for the potential to need fewer medications," the authors acknowledged.

The Controversy

David Brown, MD, of Washington University School of Medicine in St. Louis, and Rita Redberg, MD, of the University of California San Francisco, agreed with the researchers in an accompanying editorial: "We commend them for challenging the existing dogma around a procedure that has become routine, ingrained, and profitable. The results of ORBITA show (once again) why regulatory agencies, the medical profession, and the public must demand high-quality studies before the approval and adoption of new therapies."

They urged action by medical societies: "Based on these data, all cardiology guidelines should be revised to downgrade the recommendation for PCI in patients with angina despite use of medical therapy."

The Society for Cardiovascular Angiography and Interventions (SCAI) quickly signaled that it doesn't agree.

"We applaud the investigators for their innovative use of a sham procedure, but we're concerned about the reliability and interpretation of the findings. The number of patients studied was very small, so the study is far from conclusive. The primary endpoint used, exercise tolerance, is imprecise and very subjective: patient tolerance of exercise normally varies from week to week, so differences of a few seconds in exercise tolerance are hard to interpret," SCAI President Kirk Garratt, MD, said in a statement.

"The most objective measure of ischemia relief in ORBITA was a secondary endpoint of heart performance called the DSE peak stress wall motion score index. This measure was significantly improved by PCI over sham treatment. Since PCI provides benefit by relieving ischemia, this test proved that PCI worked, and can provide added benefit even with optimal medical therapy," Garratt argued.

"Andreas Gruentzig, the inventor of angioplasty, advocated for rigorous study of the technique from the start. He would approve of using a sham procedure, but I think he would have demanded a larger, longer study with less subjective endpoints."

ORBITA lead author Rasha Al-Lamee, MD, of Imperial College London, disagreed with the editorialists. “This is the first placebo-controlled trial of PCI. It may be used in guideline discussions, but guidelines should be used for whole populations.”

Importantly, the ORBITA population was relatively low-risk at baseline and presented with good exercise scores to begin with.

“To extrapolate the results to patients with high risk would be perhaps an overimplication of these results,” Al-Lamee said at a press conference. “To use this to downgrade guidelines would be an incredibly large overreach.”

The Trial

ORBITA included 230 patients with ischemic symptoms, 200 of whom underwent randomization after a 6-week medication optimization phase to ensure robust background antianginal therapy.

At five sites in the U.K., PCI recipients got DES for all lesions that were deemed to be angiographically significant, with operators mandated to achieve angiographic complete revascularization.

The trial was designed to show a 30-second difference in exercise time, which Davies and colleagues called "a relatively conservative goal for an invasive therapy that has a small but non-negligible risk."

Brown and Redberg argued that shorter follow-up would have actually worked in favor of PCI, explaining that "any haemodynamic benefit from PCI occurs early and the benefits of medical therapy continue to accrue over years."

Press conference moderator Ajay Kirtane, MD, SM, of Columbia University Medical Center/New York-Presbyterian Hospital in New York City, disagreed. “Most would argue that the placebo effect wanes over time,” he said.

In the end, Robert Yeh, MD, of Boston’s Beth Israel Deaconess Medical Center, said ORBITA was a lesson for interventional cardiologists.

“Interventional cardiologists should look at these data and offer more medical therapy upfront,” he commented. “What we don’t do is sell PCI to patients. What we do is treat them.”

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