NEW ORLEANS — Addressing a persistent controversy, a tightly blinded trial has confirmed a significant reduction of angina for patients with a chronic total occlusion (CTO) when treated with a percutaneous coronary intervention (PCI). 

Disputing the suspicion that a placebo effect explained previously reported benefit, PCI compared to a sham procedure reduced angina symptoms immediately, provided a prolonged reduction in angina, and allowed antianginal medications to be reduced or eliminated, said Sarosh Khan, MBBS, Department of Interventional Cardiology at Anglia Ruskin University School of Medicine in Essex, UK. 

As a result, the trial, called ORBITA-CTO supports PCI CTO patients for the indication of angina reduction, said Khan, who presented the results of this late breaking trial at the American College of Cardiology (ACC) Scientific Session 2026. The study was published simultaneously in the Journal of the American College of Cardiology.

Patients Required to Have J-CTO Score ≤ 3 

To eliminate confounders, the enrollment was restricted to patients with single-vessel CTO. Patients were required to have symptomatic angina and a preprocedural risk J-CTO score of ≤ 3, signifying a CTO association, relative to more complicated lesions, with reasonable likelihood of procedural success. Due to the demands of the trial and strict criteria, only 50 patients — 25 in each arm — participated.

The blinding — which included patients, ward staff, those involved in follow-up care and analysis, and the research team ­— was a key aspect of the study. Following randomization just prior to the assigned procedure, patients were sedated and wore headphones with music playing. Guide catheters were placed in the arms of both patient groups. The duration of the procedure was the same.

“As part of the study protocol, an evaluation of blinding found excellent fidelity of the patients, staff, and research team,” Kha reported.

All antianginal medications were stopped before the procedure. After the procedure, patients began recording angina with a smartphone app that they were trained to use at trial enrollment. Antianginal medications could be restarted by patient request in a stepwise predefined protocol. If a daily angina report was not entered into the app, the patient was contacted by telephone to elicit an entry.

On the primary outcome, which was a daily symptom burden in the context of antianginal medication use and one of three override events — unacceptable episode of angina, acute coronary syndrome, or death — the odds ratio of an improved angina score over the 24 weeks of follow up was 4.38 (95%, CI 1.57-12.69).

“This resulted in 30.6 angina-free days in the PCI group relative to controls,” Khan reported. 

The finding was reinforced by almost every secondary measure evaluated, including fewer angina episodes, less severe angina episodes, improvement in Canadian Cardiovascular Society angina class (> 90% vs < 50% in class 0 or 1), and improvement in quality of life.

“The between group differences emerged in follow-up immediately and the differences were sustained for the 24 weeks of follow-up,” reported Khan, who said a small proportion of patients in the treatment arm became angina-free. 

Benefits Called Moderate, Not Dramatic 

In an accompanying JACC editorial, Ziad A. Ali, MD, DPhil, director of the DeMatteis Cardiovascular Institute at St Francis Hospital and Heart Center in Roslyn, New York, wrote that even though the angina relief was “moderate rather than dramatic,” he praised the trial for finally providing evidence that “the physiological act of reopening a chronically occluded coronary artery can translate into symptomatic improvement.”

There have been numerous studies, such as the non-blinded Euro CTO trial, that have associated PCI with a reduction in angina burden in patients with CTO, but this is the first trial to provide a “true placebo-adjusted benefit” of CTO PCI, according to J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at Brown University in Providence, Rhode Island.

Abbott, the ACC-invited discussant for this trial, acknowledged the study was small but said she admired the design elements, including the blinding and eligibility factors, such as single-vessel disease, that reduced noise and better permitted a key unanswered question to be addressed.

Due at least in part to uncertainty about the value of PCI in these patients, only 6%-7% of patients with CTO currently undergo PCI in the US, Abbott reported. She said current guidelines provide a 2b recommendation for opening CTO lesions because of uncertain benefit. 

It is not clear that this study will be sufficient to change guidelines. Both Abbott and Ali were most impressed with the rigor with which ORBITA-CTO was designed to confirm that opening CTO lesions can lead to symptom benefit. But it was performed in patients with single-vessel disease at high likelihood of procedural success, which — defined as crossing of the lesion — was achieved in 96% of those who underwent PCI.

ORBITA-CTO does provide “foundational evidence” that opening CTO lesions with PCI increases the likelihood of relieving angina, but “the next challenge for the field is to determine when, and for whom, it works best,” Ali wrote in his editorial. 

Khan reported financial relationships with AstraZeneca and Vascular Perspectives. Ali reported financial relationships with Abbott, Abiomed, Acist, Amgen, AstraZeneca, Boston Scientific, Cardiovascular Systems, Elucid, LifeLink, Medtronic, OpSens, Philips, Shockwave, SpectraWAVE, and Vital Connect. Abbott reported financial relationships with Abbott, Boston Scientific, Med Alliance, Medtronic, Penumbra, and Recor.