PHILADELPHIA — Percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) reduces angina frequency, increases exercise capacity, and improves quality of life, results of a placebo-controlled, randomized trial show, confirming advantages that have never before been proven.
“The effect of PCI was immediate, sustained over 12 weeks, and consistent across all endpoints,” reported Christopher A. Rajkumar, MBBS, an interventional cardiology registrar at the Imperial College Healthcare Trust, London, UK.
Results of the trial, ORBITA-2, were presented today here at the American Heart Association Scientific Sessions 2023, and simultaneously published online in the New England Journal of Medicine.
Symptom relief has long been a justification for PCI in patients with stable CAD, but the evidence has been derived from uncontrolled studies, Rajkumar said. However, the first ORBITA trial, which was also placebo-controlled and randomized, failed to show benefit.
Rajkumar acknowledged that the benefit of PCI in ORBITA-2 was lower than previously reported in nonrandomized trials. He also noted that 59% of patients still had at least some angina symptoms following PCI.
Even though ORBITA-2 proves that PCI is better than no PCI, he agreed that well-informed patients, such as those who wish to avoid an invasive procedure, might still reasonably select antianginal medication over PCI. Current guidelines recommend PCI for patients with refractory angina despite medical therapy.
While Rakjumar was unwilling to speculate on how these data might change guidelines, he did say that patients with stable CAD and angina “now have a choice of two first-line evidence-based pathways.”
“ORBITA 2 is a rather remarkable trial because my surgical colleagues have been asking me for many decades whether PCI actually works,” said Martin B. Leon, MD, professor of medicine, Columbia University Irving Medical Center, New York City.
“Now I can say with confidence on the basis of a placebo-controlled trial that PCI certainly does have a favorable impact in patients with documented angina, severe coronary stenosis, and demonstrated ischemia.”
The key enrollment criteria for ORBITA-2 were angina, severe coronary stenosis in at least one vessel, and ischemia on stress imaging or invasive physiology. Unlike the previous ORBITA trial, which was limited to single-vessel disease and did not require objective evidence of ischemia, ORBITA 2 employed change in angina, rather than improved exercise capacity, as its primary endpoint.
Relative to sham PCI, patients randomly assigned to an interventional procedure had a more than twofold increase in the odds ratio of improved angina control (OR, 2.2; P < .001) based on a patient scoring system that captured angina symptoms as well as angina medication use on a smartphone application.
The advantage of PCI over sham PCI was also significant for all secondary outcomes. These included a nearly fourfold greater (OR, 3.76; P < .001) likelihood of improvement in the Canadian Cardiovascular Society (CCS) angina grade and a 1-minute increase (from 10 min. 40 seconds to 11 min. 40 seconds) in treadmill exercise time (P = .008).
On quality of life measured with the self-assessment questionnaire (SAQ) and the EQ-5D-5L, almost all endpoints were highly statistically significant in favor of PCI (typically on the level of P < .001).
The study had a bold design: At enrollment patients stopped all antianginal medications to undergo dobutamine echocardiography and other baseline tests. They were stopped again 2 weeks later, when patients were randomized.
With a study protocol that enrolled patients off medication, “we intentionally diverged from the clinical guidelines,” Rajkumar said.
Of the 439 patients enrolled, 301 were randomly assigned at the end of the 2-week period, when patients were already sedated. Control patients remained sedated for at least 15 minutes. All 151 of those randomized to PCI and the 150 control patients were available for the intent-to-treat analysis at the end of 12 weeks.
The novel angina symptom burden score was created from daily angina episodes and units of daily antianginal medication captured on the smartphone app. On an ordinal scale, a score of 0 on any given day represented no anginal symptoms and no antianginal medication.
As angina severity or medication use increased, it raised the daily scores. If there was unacceptable angina (requiring the patient to be removed from the blind), acute coronary syndrome, or death, it produced the highest scores, which reached a maximum of 79.
The favorable odds ratio for a lower symptom burden in the PCI group reflected a relative reduction in angina observed the first day after the procedure. Over the entire follow-up, more patients in the PCI group had an angina score of 0 and more of those who had angina did not take antianginal medications.
This objective evidence that PCI reduces symptoms and improves quality of life in patients with angina and stable CAD was met at the AHA late-breaking session with a sustained ovation.
ORBITA-2 Addresses ORBITA Criticisms
Connie N. Hess, MD, the AHA-invited discussant and an interventional cardiologist at the University of Colorado Medicine, provided perspective on the differences between ORBITA 2 and ORBITA, which she said “addressed a fundamentally different hypothesis” by focusing on angina rather than exercise capacity.
Of the criticisms of the original ORBITA, which Hess noted was the first sham-controlled PCI trial ever conducted in stable CAD, one is that patients with multivessel disease were excluded, another was that objectively proven ischemia was not required, and a third was that the study of 6 weeks had a short duration.
“ORBITA 2 addressed many of these concerns,” Hess said, but, when noting that 80% of patients in the newer trial still had single vessel disease, she questioned whether the true effect of PCI for improving symptoms might still be underestimated.
ORBITA-2 was supported by the National Institute for Health and Care Research ( NIHR) Imperial Biomedical Research Centre, the Medical Research Council, NIHR, the British Heart Foundation, Philips, and St. Mary’s Coronary Flow Trust.
Rajkumar reports relevant financial relationships. Leon reports financial relationships with Abbott Vascular, Anteris, Boston Scientific, Edwards Lifesciences, Foldax, and Medtronic. Hess has financial relationships with more than 20 pharmaceutical companies, but none related specifically to this presentation.
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