In carefully selected patients with symptomatic single-vessel chronic total occlusion, CTO PCI improved angina symptoms compared with a placebo procedure, supporting CTO PCI as a true symptom-relief intervention beyond placebo effect when performed in appropriate patients by experienced CTO operators.
Study design
- Multicenter, randomized, blinded, placebo-controlled trial
- First placebo-controlled trial specifically evaluating CTO PCI
- CTO PCI vs sham/placebo procedure
- Blinding maintained with auditory isolation, deep conscious sedation, and overnight stay
- Antianginal medications stopped at randomization and reintroduced using a patient-initiated protocol
- N = 50 randomized
- Follow-up: 24 weeks
Population
- Stable angina or angina equivalent attributed to a CTO
- Single-vessel coronary CTO
- No significant bystander coronary disease
- Evidence of ischemia and viability in the CTO territory
- J-CTO score ≤3
- Accepted for CTO PCI by specialist CTO operator/heart team
- Median age 64 years
- Most patients were male
Interventions
- CTO PCI: 25
- Placebo procedure: 25
- All patients underwent invasive angiography with bilateral access
- Placebo arm underwent a sham procedure designed to mimic CTO PCI
- Successful CTO crossing achieved in 96% of PCI patients
- Approximately 30% of CTO PCI cases required a retrograde approach
Primary outcome
- Angina symptom score at 24 weeks
- Score incorporated daily angina episodes, antianginal medication use, and override events
- CTO PCI significantly improved angina symptom score vs placebo
- OR 4.38; 95% credible interval 1.57-12.69
- Probability of benefit: 99.6%
- Primary endpoint met
CTO PCI vs Placebo
Primary endpoint: improved angina symptom score at 24 weeks
OR 4.38 | 95% CrI 1.57-12.69
Primary endpoint: odds of improved angina symptom score at 24 weeks compared with placebo.
Secondary outcomes
- CTO PCI produced approximately 30.6 additional angina-free days over 168 days
- Angina frequency improved more with CTO PCI than placebo
- Seattle Angina Questionnaire domains improved, including angina frequency, physical limitation, and quality of life
- Physician-assessed CCS angina class improved with CTO PCI
- No clear difference in antianginal medication use during follow-up
- No deaths or myocardial infarctions occurred during follow-up
Safety
- No deaths reported
- No myocardial infarctions reported
- No withdrawals due to worsening angina
- One patient randomized to PCI was withdrawn during the procedure because of a complication
- Trial was small and not powered for hard clinical safety endpoints
Interpretation
- ORBITA-CTO shows that CTO PCI provides true placebo-adjusted angina benefit in selected patients
- The benefit was symptomatic, not a demonstrated reduction in death or MI
- Results apply best to symptomatic single-vessel CTO with documented ischemia/viability and J-CTO ≤3
- Generalizability is limited by small sample size, highly selected anatomy, and experienced CTO operators
- CTO PCI should remain a symptom-driven intervention rather than routine revascularization for all CTOs
Khan, S., Sajjad, U., Fawaz, S., et al. (2026). A randomized, placebo-controlled trial of chronic total occlusion percutaneous coronary intervention in stable angina: The ORBITA-CTO trial. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2026.03.027