PCI, the Antianginal 'Pill': ORBITA-2 in Detail

Michelle O'Donoghue interviews the sham PCI controlled trial investigators on the role of stents in the management of stable angina in light of both ORIBTA studies.
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Michelle L. O'Donoghue, MD, MPH: Hi. This is Dr Michelle O'Donoghue, reporting for Medscape. We're here in Philadelphia at the American Heart Association Scientific Sessions where one of the big stories has been ORBITA-2. The primary results were presented. Joining me here today are Rasha Al-Lamee and Chris Rajkumar, both from Imperial College in the UK. Before we talk about ORBITA-2, perhaps you could set the stage, Rasha; where were we at after ORBITA-1? What were the takeaways there?
ORBITA-1 Recap
Rasha Al-Lamee, MBBS, MA, PhD: Thank you very much, Michelle, for having us here. After ORBITA-1, you will remember well the fallout that came. Obviously, it was the first placebo-controlled trial of stable coronary artery disease and percutaneous coronary intervention (PCI), comparing PCI with a placebo procedure in patients who had guideline-directed medical therapy.
Importantly, the patients were on an average of three antianginal agents prior to being randomized. And what we found was that the benefit of angioplasty above placebo was far smaller than we expected, and in fact, not statistically significant on the primary endpoint of exercise time. Broadly, there was very little to talk to in terms of symptom relief; one in five more patients were free of angina. But otherwise, all of the symptoms and quality-of-life endpoints did not show a benefit for PCI, and so it left us in a weird space.
It was followed on by the ISCHEMIA trial, and people started to wonder about the role of angioplasty in stable coronary artery disease. For us, it was still important to think about symptoms and which patients might benefit from angioplasty, because we'd seen a signal that there was some benefit in those ORBITA patients, but just not in all of them. So that got us thinking about what factors in ORBITA-1 contributed to that surprising result. One of the factors was that they were on such high levels of antianginal medication, probably levels that are not what we're doing in the real world. Well, that's certainly what the data tell us, and our patients were telling us that it was too much for them and something that was difficult to sustain and adhere to over the long term. So the question became: What does angioplasty do in a more real-world setting, in a setting of patients without antianginal medication? Importantly, that question, and designing the trial that way, would allow us to work out the efficacy of angioplasty without any attenuating effects of medical therapy. That's what brought us to ORBITA-2.
O'Donoghue: ORBITA certainly got a lot of people talking, as you say. It's the first time that we really had - however you want to describe it - a sham procedure, in essence, depending on which treatment arm they were in. I think that after the COURAGE trial, there was some acceptance that perhaps for a stable angina patient, doing a PCI may not reduce the risk of death or myocardial infarction, but certainly we believed that it was going to offer symptomatic relief. I think after ORBITA-1, people paused and said, "Gee, if there's a sham procedure done, then people may derive as much benefit." But as you say, it was on a background of maximal antianginal therapy. But it's interesting, nonetheless, that people were still symptomatic despite the fact that they were on maximal antianginal therapies.
Al-Lamee: As you point to ORBITA-1, it is still a very important trial in my mind, and one that's very dear to my heart because it sets standards for how we do these trials. In performing ORBITA-1, we were able to understand that trials like this were feasible and ethical, and therefore it was easier to do a bigger trial that encompassed a broader set of patients that was more real-world to answer the question more clearly.
O'Donoghue: So that transitions us nicely to ORBITA-2. Chris, can you walk us through the design there and the topline results.?
ORBITA-2 Symptom Assessment and Sham Procedure
Christopher A. Rajkumar, MBBS, PhD: ORBITA-2 was a placebo-controlled trial of PCI for stable angina. As you mentioned, we took many of the aspects of ORBITA-1 in that these patients had undergone a coronary computed tomography angiography or a diagnostic coronary angiogram showing us evidence for an anatomical stenosis. We enrolled them into a symptom assessment period, which ran for 2 weeks prior to randomization. During this time, they documented their angina symptoms every single day using a dedicated smartphone app, which was something totally novel for this trial. They reported to us every day whether they'd had any angina and how many episodes occurred.
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