Putting ORBITA into perspective: PCI not a sham

Editor’s Note: The following is a commentary from Kirk N. Garratt, MD, MSc, FSCAI, president of the Society for Cardiovascular Angiography and Interventions and John H. Ammon Chair of Cardiology, chief of the cardiology section and associate medical director of the Center for Heart & Vascular Health at Christiana Care Health System in Delaware, about the results of the ORBITA trial of patients with stable ischemic heart disease on optimal medical therapy, which found no difference in exercise time at 6 weeks between those assigned PCI and those assigned a sham procedure.

A new study has sparked a controversial dialogue within the cardiology community about the effectiveness of PCI for specific patient populations. While new research and the exchange of ideas drive innovation and, ultimately, improve patient outcomes, we need to be careful in the way we interpret study results. Discussions among colleagues are certainly encouraged, especially within the medical community, but it is our collective responsibility to guard against snap judgments or shortsighted conclusions.

During the last 40 years, clinical studies and evidence-based research have defined the benefits of PCI. This procedure is the foundation of interventional cardiology and has been widely embraced. PCI has been proven to save lives when patients have unstable heart trouble such as MI. It’s also the preferred treatment for patients with stable ischemic heart disease who have limiting symptoms despite good medical therapy. Today, more than 13 million people in the United States have ischemic heart disease (or CAD), and nearly 9 million have angina. PCI typically involves placement of a stent to relieve a heart artery blockage, improve blood flow and relieve angina. In routine practice, PCI has been reliably effective for this purpose and has improved the quality of life of millions of people.

The benefits of PCI have come into question most recently with a first-of-its-kind, multicenter, masked, randomized study called ORBITA, presented at the TCT meeting in Denver. This study compared the efficacy of PCI plus optimal medical therapy against sham PCI plus optimal medical therapy in patients with stable ischemic heart disease.

ORBITA studied 200 patients who had stable but limiting anginal symptoms. Each patient had a stress test, then underwent intensive, supervised medical therapy optimization for 6 weeks prior to invasive treatment. After 6 weeks, patients underwent heart catheterization that included fractional flow reserve measurements of targeted blockages, to assure these blockages were causing ischemia. The blockages were then treated with PCI or a sham PCI, in which equipment was inserted into the patient, but no actual angioplasty was performed. Neither patients nor physicians were aware of their treatment assignment. The objective of ORBITA was to test whether differences in exercise tolerance, quality of life and symptom relief after invasive treatment were real or simply a placebo effect. Six weeks after the procedure, patients were questioned about symptoms and underwent a second exercise stress test. Exercise duration at 6 weeks was compared with exercise duration at baseline for each patient, and the average change in exercise tolerance for the PCI group was compared with the average change in the sham-treated group. Both groups had better exercise tolerance after treatment. The difference in average improvement between the two groups was not statistically significant. PCI-treated patients improved by 28.4 seconds while sham-treated patients improved by 11.8 seconds.

As a clinician-scientist, I admire the use of a sham procedure. The placebo effect is a consistent phenomenon, observed to some degree in nearly all placebo-controlled trials. Furthermore, there is evidence that sham procedures trigger a stronger placebo effect than sham pills or noninvasive treatments. ORBITA seems to confirm that PCI is not immune to the placebo effect. But that doesn’t mean PCI is a sham.

The primary endpoint in ORBITA, change in exercise tolerance, is relatively imprecise and subjective. Patient tolerance normally varies from week to week. As a result, differences of just a few seconds of exercise tolerance are difficult to interpret. Patients were given three times as many heart pills than they usually took during the 6 weeks before PCI or sham procedure. Consequently, one of nine patients did not have any symptoms. Such patients would not be offered PCI in clinical practice because we don’t expect PCI to provide any additional benefit. Roughly one-quarter of patients who underwent randomization had class 0 or I angina, that is, so little symptoms that even highly effective treatments would have minimal impact.

Other concerns are more typical of these studies: Stable angina patients are abundant, yet it took five hospitals 3.5 years to find just 368 eligible patients, raising questions of selection bias and generalizability of findings. Exercise time was, in fact, greater for patients assigned PCI, and the same final findings in a larger study could easily have been positive for PCI. There’s also the interesting question of nicorandil, a vasodilator with potassium-ATP channel blocking properties. This medication, which is not available for clinical use in the U.S., works like a nitrate but has been proven to reduce symptoms when nitrates are not effective. Nicorandil use at randomization was significantly greater in the sham group, the impact of which is uncertain.

Studies like ORBITA fuel debate and are imperative for the advancement of medicine. We need, though, to couch new findings in the context of earlier works. In the case of ORBITA, the findings are not sufficiently compelling to change convictions or practices. Rather, ORBITA shows us that sham-controlled studies are possible for PCI and suggests that their use may be helpful in further defining the full benefits of invasive therapies.

We should and will continue to work together to push boundaries, advance medicine and improve the lives of our patients. Through that process, we can be confident that we’ll define the best ways to use invasive therapies in the care of our patients.

For more information:

Kirk N. Garratt, MD, MSc, FSCAI, can be reached at 252 Chapman Road, Suite 150, Newark,

DE 19702; email: kgarrattmd@gmail.com.

Disclosure: Garratt reports no relevant financial disclosures.