‘Immediate’ Return to Normal Flow Post-PCI in ORBITA-Like Patients

For patients with stable coronary artery disease, undergoing PCI improves coronary blood flow as well as other systemic and hemodynamic responses during exercise, and these beneficial changes are associated with large gains in patient symptoms and exercise tolerance, a new study shows.

Although patients were unblinded to the procedure, investigators conclude that PCI eliminated the stenotic resistance associated with the coronary lesion, which restored the vessel to its “primary role as a conduit” and allowed the microcirculation to progressively vasodilate during exercise.   

“If you think about a medical treatment that takes you from a disease state to a normal state immediately, there’s very few therapies I can think of that are that effective,” lead investigator Christopher Cook, MBBS (Imperial College London, England), told TCTMD.  

In an editorial, Morton Kern, MD (University of California, Irvine), and Arnold Seto, MD (VA Long Beach Health Care System, CA), say the present study “represents one of the best human physiological studies demonstrating the mechanisms of benefit from stenosis relief by stenting.” For truly ischemic lesions, “PCI works, relieving ischemia and angina, and likely works much better than medical therapy,” they write.

To TCTMD, Ajay Kirtane, MD (Columbia University Irving Medical Center, New York, NY), who was not involved in the small study, was impressed by it, particularly with the exercise protocol while patients were still on the cath lab table. However, he wasn’t surprised by the benefits of the PCI procedure, despite the criticisms, specifically those stemming from the ORBITA trial, that the benefits of stenting were largely psychological.

“We have a clear physiologic change and impact that we’re measuring,” he said. “There’s a physiologic impact and there’s the placebo effect, but there is clearly something going with the physiology and this study shows it. . . . In the current era, and coming from the ORBITA investigators, it’s commendable they were able to come out with this analysis.”

Improved Exercise Capacity and Other Measures

The study, published in the August 28, 2018, issue of the Journal of the American College of Cardiology, included 21 patients with stable coronary artery disease and a single-vessel coronary stenosis who underwent cardiac catherization as part of the ORBITA trial. Before PCI, patients exercised on a supine ergometer until exhaustion (or rate-limiting angina) and transstenotic coronary pressure-flow measurements were taken throughout exercise. After PCI, the process was repeated.

Conceptually, physicians understand that PCI “works” by removing the coronary stenosis and increasing blood flow through the coronary arteries, but flow is not measured in clinical practice, said Cook. Instead, pressure surrogates, such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), are used. As a result, physicians are more accustomed to thinking about ischemia in terms of coronary pressure.

“For us, it was really important to understand the mechanisms of angina and its alleviation by PCI,” said Cook. “We really had to measure coronary pressure and coronary flow.”

He noted that other research groups, including those from King’s College and St. Thomas’ Hospital in London, have pioneered the testing of exercise coronary physiology, including those that have utilized coronary pressure and flow measurements during exercise to understand angina. “However, what was really lacking from the database of studies was one that investigated PCI and PCI’s role in exercise hemodynamics,” said Cook.

Among the 21 patients, 95% tested before PCI stopped exercising because of breathlessness or chest pain. After PCI, only 10% of patients stopped exercising for these reasons, with the remainder stopping because they became physically tired without chest pain or breathlessness. Exercise time increased by 67 seconds after stenting the coronary lesion, and rate-limiting angina symptoms declined by 81%.   

Prior to PCI, systolic blood pressure increased with exercise but then dropped when symptoms developed. Following PCI, however, systolic blood pressure rose with exercise and plateaued with peak exercise but did not decline. The rate pressure product—a measure of myocardial workload—at peak exercise was also improved following PCI. 

Additionally, PCI improved coronary circulation, with both FFR and iFR increasing following the procedure. PCI also resulted in an improvement in coronary flow reserve. Coronary flow velocity increased in a “near-linear” manner with exercise following PCI and was 65% higher at peak exercise after PCI than before the procedure. Distal coronary pressure, transstenotic pressure gradient, transstenotic pressure ratio, and stenosis resistance were also significantly improved during all stages of exercise after PCI.

Cook said the results reflect the “upstream and downstream beneficial effects” of PCI, with normalization of physiology across three domains: systemic circulation, coronary circulation, and microcirculation. 

As for how the present study fits into the context of ORBITA, Cook said the studies “complement” one another, with both showing PCI leads to an improvement in ischemia as assessed using FFR and iFR measurements. Recently, the ORBITA investigators reported that FFR and iFR values tracked closely with improvements on stress echocardiography, with patients with lower baseline FFR or iFR values having a larger magnitude of ischemia benefit after PCI.

“What’s different between our two studies is that in ORBITA, when the patient is unaware whether they have had stenting or not, that seems to be a critical step in the process,” said Cook. “It means they don’t go on to attain the maximal clinical benefit in terms of being able to exercise further or have a greater reduction in symptoms compared with placebo.”

‘Doesn’t Take Weeks, Doesn’t Take Months’

Speaking with TCTMD, Seto was also impressed with the study protocol. “They showed that exercise capacity immediately improved after PCI,” said Seto. “It doesn’t take weeks, it doesn’t take months.” Moreover, the study contradicts the initial headlines from the ORBITA trial—with some newspapers stating stents were “useless” for stable disease—because these results demonstrate there is benefit of relieving the stenosis in selected patients with ischemic single-vessel coronary artery disease, he said.

“The results aren’t too surprising to any interventionalist that PCI works to relieve ischemia and relieves ischemia-related symptoms,” said Seto. “The challenge in testing the effectiveness of PCI is really in selecting the population. That’s what this study shows us. In finding the patient with classic chest pain symptoms and an ischemic lesion, relieving that stenosis will relieve their pain.”    

For Cook, one of the strengths of the study is that the researchers allowed patients to exercise until they developed symptoms—not just a surrogate marker of ischemia, such as an ST change on the ECG—which allowed them to assess the true impact of PCI on angina symptoms. This is particularly important given the renewed interest in stable coronary artery disease and the focus on patient symptoms. Additionally, Cook said despite the extended study protocol, patients were grateful for the opportunity to maximally exercise, and this spurred many patients to embrace a healthy lifestyle after PCI. 

“It wasn’t something I was expecting,” said Cook. “I thought there’d be altruistic element for contributing to science, but they really took a psychological benefit from exercising so hard and from doing so well after stenting.”