Circling Back on ORBITA: Sham-Controlled PCI Trial Makes Best of 2017 List

ANAHEIM, CA—Less than 2 weeks after its presentation, the ORBITA trial has made it onto a list of the most important interventional trials of 2017. 

The selection of ORBITA, which was presented at TCT 2017 and published just 10 days ago in the Lancet, likely surprised few clinicians who have followed its wide-ranging reception and the vocal debate over the study’s findings. However, there were more than a few chuckles when Robert Yeh, MD (Beth Israel Deaconess Medical Center, Boston, MA), who presented the year’s “best interventional trials” here today at the American Heart Association 2017 Scientific Sessions, said the study was designed “to ask whether PCI even works.”

In total, five studies made the “best of 2017” list, including COMPARE-ACUTE, CULPRIT-SHOCK, RE-DUAL PCI, SENIOR, and ORBITA, although DEFINE-FLAIR/iFR-SWEDHEART, DK-CRUSH, and RAD-MATRIX received honorable mentions. All of the studies have been covered in depth by TCTMD over the course of the year.

No recent trial, however, especially one so small and with just 6 weeks of follow-up, has polarized physicians as much as ORBITA. In a rundown of the study, Yeh said the trial “put a sacred belief to the test,” that being whether or not PCI reduced symptoms when compared with a sham procedure.

In the ORBITA trial, change in exercise time, the primary endpoint, improved significantly from baseline in stable patients with single-vessel coronary artery disease who underwent PCI, with nonsignificant improvements also seen in patients given the sham procedure. Importantly, however, no significant differences were seen between the two arms for that primary endpoint, or for measures of symptom improvement and quality of life. Ischemia, as assessed by dobutamine stress echocardiography, was significantly reduced with PCI.

In his “mild” interpretation of the study, Yeh said that for stable patients with single-vessel coronary artery disease initially maximized on medical therapy, “PCI has a modest benefit for improving symptoms in the first 6 weeks, but it reduces ischemia.” Additionally, Yeh stated that maximally tolerated optimal medical therapy is also a very effective initial treatment strategy for these patients.

What Would You Do?

During the presentation, Yeh highlighted numerous details of the study to put the ORBITA results in perspective: the blinding procedure, patient inclusion criteria, lesion characteristics, and fractional-flow reserve (FFR) measurements. He also noted that the investigators provided angiographic images of all the lesions treated in the trial, “and one has to concede that these are the types of lesions that we do in practice every day, perhaps even without FFR.”

Yeh then turned the question to his audience: “The next time you see a patient with class II or III angina taking one antianginal and 70% stenosis in the proximal [left anterior descending] artery, do you plan to take the patient off the table and intensify medical therapy and offer PCI only if there are continued symptoms? Do you perform PCI now while maximizing medical therapy afterwards? Or do you perform FFR/iFR and then do PCI if [the lesion] is functional significant?”

The vast majority of the audience suggested they would perform a functional assessment of the identified lesion before proceeding to PCI.

Speaking with TCTMD about the ORBITA results, Mamas Mamas, BMBCh (Keele University, Stoke-on-Trent, England), said that while he is a proponent of FFR, stable CAD patients have typically had noninvasive testing with documented ischemia before they end up in the catheterization laboratory.

“If the ischemia on the noninvasive test tallies up with the distribution of disease then I wouldn’t do FFR,” said Mamas. “If you have anterior ischemia on the stress [cardiac magnetic resonance] and you have an LAD lesion, there’s no point doing a pressure wire. You just stent it. In other cases, if I don’t have that information, or there is a discrepancy—for example, there is inferior ischemia burden but the lesion is in the LAD territory—in those cases I will generally do a pressure wire unless the lesion is so significant I would be worried about disrupting it with a pressure wire.”

On the whole, in the United Kingdom, most patients would have a noninvasive test before they get onto the table for a diagnostic cath, said Mamas.

Fascinating and Sobering

Speaking during the session today, Dean Kross, MD (Heart Care Medical Associates, Pittsburgh, PA), said ORBITA is “fascinating” in that medical therapy was proven equal to PCI in patients with stable coronary artery disease. “We’ve kind of known that for years, yet there have been billions spent on needless stenting and interventions,” he said during the AHA session. “That should be very sobering to anybody who does interventions.”

Yeh agreed, adding that the same rigor should also be applied to other aspects of cardiology, such as noninvasive testing and ablation of atrial fibrillation. Asked about the 6-week endpoint, and whether or not it is sufficient to show a benefit, Yeh said the argument can be made for and against the trial’s short duration.

“I think when we do PCI for ischemic lesions in symptomatic patients, I tell my patients they’re going to get better right away and they often do,” said Yeh. “So, from that standpoint, it’s reasonable to say they should have gotten better sooner. Where the 6 weeks is a question mark is whether the intensity of medical therapy can be sustained for that long. Maybe there are patients who can’t sustain that and fall off, or maybe become symptomatic. Maybe the placebo effect wears off over time. It’s not clear.”

As to another question that’s been making the rounds over the last 10 days—whether ORBITA could have been performed in the United States—session moderator Manesh Patel, MD (Duke University School of Medicine, Durham, NC), said it might have been difficult, but pointed to the fact that institutional research boards in the US have previously allowed sham-controlled trials of renal denervation.