First published placebo-controlled trial shows benefit in difficult-to-treat condition

NEW ORLEANS (March 29, 2026) — In what is believed to be the first randomized placebo-controlled trial of its kind, patients with a chronic total blockage of a coronary artery who received a nonsurgical procedure to reopen the artery showed statistically significant reductions in chest pain and improvements in quality of life compared with patients who received a placebo procedure. The research was presented at the American College of Cardiology’s Annual Scientific Session (ACC.26).

“Our results demonstrate in a randomized, double-blinded study design that coronary angioplasty and stenting is an effective treatment for patients who have a chronic total occlusion and chronic anginal chest pain,” said principal investigator John Davies, MRCP, PhD, a consultant interventional cardiologist at the Essex Cardiothoracic Center and honorary lecturer at Anglia Ruskin University School of Medicine in the United Kingdom.

A chronic total occlusion (CTO) is a total blockage of a coronary artery (a blood vessel that carries blood to the heart muscle) that has been present for three months or more. It’s caused by a condition known as atherosclerosis, which is a buildup of fatty deposits, or plaque, in the artery over time. Different from a heart attack, which is caused by a sudden blockage of a coronary artery due to a blood clot, a CTO is often accompanied by angina, a pain or feeling of constriction in the chest that can occur at rest or, more frequently, with any physical exertion.

Studies have shown that among patients undergoing coronary angiography (a heart X-ray), around 30% are found to have a CTO, while among patients with a history of coronary artery bypass surgery, more than 50% are found to have CTOs in untreated blood vessels. The condition most commonly occurs in people over the age of 40 who have risk factors that predispose them to atherosclerosis, such as smoking, high blood pressure, high cholesterol, diabetes and a family history of angina, heart attacks and treatment of coronary blockages. It is frequently undertreated, reducing patients’ quality of life, Davies said.

In many cases, coronary arteries that are partially blocked by plaque can be treated with percutaneous coronary intervention (PCI) or angioplasty, a procedure in which a tiny balloon is placed inside the artery and a stent (a small, wire-mesh tube) is placed at the site of the blockage to keep the artery from becoming blocked again.

However, it’s challenging to perform angioplasty in a totally blocked artery, Davies said. For one thing, the plaque has often hardened over time, making the procedure more technically difficult. Compared with standard angioplasty, angioplasty for CTO is much more time-consuming to perform (typically three hours instead of under 60 minutes); requires advanced techniques, equipment and an experienced operator; and has a lower success rate and a higher risk for complications.

“Procedures like angioplasty can often have large placebo effects because patients are expecting to get better,” Davies said. Yet no previously published study of angioplasty for CTO had compared it with a placebo procedure, where angioplasty was not carried out. The ORBITA-CTO trial was designed to fill that gap by determining whether angioplasty would actually reduce angina and improve quality of life in patients with CTO.

The trial enrolled 50 patients (median age 64 years, 74% men) at two sites in the UK. All the patients had a completely blocked coronary artery present for at least three months and had symptoms of angina for an average of 12 months despite taking anti-anginal medication. They were randomly assigned to receive either angioplasty for CTO (the intervention group) or a placebo procedure (the control group). To ensure patients were blinded to their assigned treatment, they were sedated before the procedure and during the procedure listened to music through headphones so they could not overhear the members of the medical team talking. The medical team that followed the patients afterward also did not know who had received angioplasty and who had received the placebo procedure.

The trial’s primary endpoint was an angina score comprising the number of daily episodes of angina that patients experienced and recorded on a smartphone app, and the number and doses of anti-anginal medication they took during the 24-week follow-up period. Key secondary endpoints were patients’ scores on a quality-of-life questionnaire and a blinded physician assessment of the severity of patients’ angina.

While the results showed that angina scores improved in the placebo group, indicating that the patients had fewer episodes of angina and needed fewer or lower doses of anti-angina medication, patients in the CTO angioplasty group were four times as likely to have improved angina scores, a finding that was highly statistically significant. On average during the 168-day follow-up period, the patients who received CTO angioplasty had 31 more angina-free days than those in the placebo group.

Patients in the intervention group also saw a statistically significant improvement in their quality-of-life scores and a reduction in the physician-assessed severity of their angina, compared with those in the placebo group. No patients died, had a heart attack or had to withdraw from the study due to worsening angina.

The study has several limitations. With just 50 patients, it was relatively small, and all patients were treated in specialized centers by experienced operators. Patients with the most complex CTO features were also excluded from the study, and the results cannot be extrapolated to these patients. Despite its small size, the design and execution of the study were exemplary, resulting in high-quality robust data, Davies said. Further research is required to determine the effectiveness of CTO angioplasty in patients with highly complex CTO and to identify more precisely the patients likely to benefit the most from CTO angioplasty.

“These results provide hope for both patients with CTO and their doctors that angioplasty with stenting can be successful and can result in reduced angina pain and better quality of life,” Davies said.

The study was funded by a grant from Abbott Vascular.

This study was simultaneously published online in the JACC at the time of presentation.

Sarosh Khan, the study’s lead author, will present, “A Randomized, Placebo-controlled Trial of Chronic Total Occlusion Percutaneous Coronary Intervention In Stable Angina- ORBITA-CTO Trial,” on Sunday, March 29, at 8:30 a.m. CT / 13:30 UTC in the Main Tent, Great Hall. 

ACC.26 will take place March 28-30, 2026, in New Orleans, bringing together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC26 for the latest news from the meeting.

The American College of Cardiology (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of JACC Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart.org patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at ACC.org.

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