First Placebo-Controlled Trial Shows Angioplasty Significantly Reduces Angina in Chronic Total Occlusion Patients
Key Insights
The ORBITA-CTO trial represents the first randomized, placebo-controlled study demonstrating that angioplasty (search) significantly improves angina (search) symptoms in patients with chronic total coronary occlusions.
Patients who received angioplasty (search) were four times more likely to have improved angina (search) scores and experienced 31 more angina-free days compared to those receiving a sham procedure.
The study enrolled 50 carefully selected patients with single-vessel chronic total occlusions and used extraordinary blinding measures to eliminate placebo effects.
Patients with chronic total coronary occlusions who underwent angioplasty (search) showed statistically significant reductions in chest pain and improvements in quality of life compared with patients who received a placebo procedure, according to results from the first randomized placebo-controlled trial of its kind. The ORBITA-CTO trial findings were presented at the American College of Cardiology (search)'s Annual Scientific Session (ACC.26).
"Our results demonstrate in a randomized, double-blinded study design that coronary angioplasty (search) and stenting (search) is an effective treatment for patients who have a chronic total occlusion (search) and chronic anginal chest pain," said John Davies, MRCP, PhD, principal investigator and consultant interventional cardiologist at the Essex Cardiothoracic Center (search) and honorary lecturer at Anglia Ruskin University School of Medicine (search), United Kingdom.
Understanding Chronic Total Occlusions
A chronic total occlusion (search) (CTO) is a total blockage of a coronary artery (search) that has been present for three months or more, caused by atherosclerosis (search)—a buildup of fatty deposits or plaque in the artery over time. Unlike a heart attack caused by sudden blockage due to a blood clot, a CTO is often accompanied by angina (search), chest pain that can occur at rest or with physical exertion.
Studies show that among patients undergoing coronary angiography, around 30% are found to have a CTO, while among patients with a history of coronary artery (search) bypass surgery, more than 50% have CTOs in untreated blood vessels. The condition most commonly occurs in people over age 40 with atherosclerosis (search) risk factors including smoking, high blood pressure, high cholesterol, diabetes, and family history of coronary disease.
Trial Design and Methodology
The ORBITA-CTO trial enrolled 50 patients (median age 64 years, 74% men) at two UK sites. All patients had a completely blocked coronary artery (search) present for at least three months and experienced angina (search) symptoms for an average of 12 months despite taking anti-anginal medication (search). Patients were randomly assigned to receive either angioplasty (search) for CTO or a placebo procedure.
To ensure proper blinding, patients were sedated before the procedure and listened to music through headphones during the procedure so they could not overhear medical team conversations. The medical team following patients afterward also remained blinded to treatment assignments.
"We removed all the clocks from everywhere—from the lab, the corridors, the wards—and all of the patients stayed overnight," Davies explained. During sham procedures, operators spent an hour mimicking angioplasty (search) movements and gave two 1-minute infusions of IV adenosine to simulate symptoms.
Significant Symptom Improvement
The trial's primary endpoint was an angina (search) score comprising daily episodes of angina recorded on a smartphone app and anti-anginal medication (search) usage during the 24-week follow-up period. While angina scores improved in the placebo group, patients in the CTO angioplasty (search) group were four times more likely to have improved angina scores—a highly statistically significant finding (OR 4.4; 95% CI 1.6-12.7).
On average during the 168-day follow-up period, patients who received CTO angioplasty (search) had 31 more angina (search)-free days than those in the placebo group. The intervention group also showed statistically significant improvements in quality-of-life scores and physician-assessed angina severity compared to the placebo group.
"It proves that CTO PCI improves angina (search) symptoms, which is immediate, sustained, and consistent," Davies said. "This supports symptom-driven PCI in carefully selected patients, through the heart team selection, in centers with specialist CTO operators."
Study Limitations and Clinical Implications
The study has several limitations, including its relatively small size of 50 patients and treatment only in specialized centers by experienced operators. Patients with the most complex CTO features were excluded, and results cannot be extrapolated to these patients. The two treating physicians each performed at least 200 CTOs annually, representing highly experienced operators.
Sergio Waxman, MD, who wasn't involved in the study, noted the trial's selective population: "These are patients with just a single-vessel CTO and no other significant coronary artery disease (search). The trial was very well conducted, obviously, just an incredible design, and they were meticulous in trying to adjust for all different confounding variables."
Despite the small size, Davies emphasized that "the design and execution of the study were exemplary, resulting in high-quality robust data." No patients died, had heart attacks, or withdrew due to worsening angina (search).
Future Research Directions
Further research is required to determine CTO angioplasty (search) effectiveness in patients with highly complex CTOs and to identify more precisely which patients would benefit most from the procedure. The study excluded patients with J-CTO scores of 4-5 to avoid significant failure rates, though investigators noted that J-CTO lesions ≤ 3 still represent challenging cases, with about 30% requiring a retrograde approach.
"These results provide hope for both patients with CTO and their doctors that angioplasty (search) with stenting (search) can be successful and can result in reduced angina (search) pain and better quality of life," Davies concluded.
The study was funded by Abbott Vascular and simultaneously published online in the Journal of the American College of Cardiology (search) at the time of presentation.