A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina

Abstract

Background: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown.

Methods: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina.

Results: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group.

Conclusions: Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).

Figure 1. Primary end point of angina symptom score and its constituents.

Panel A shows the individual patient data composition of the primary end point (angina symptom score) stratified by treatment allocation. The method for derivation of the score is depicted below and the overall calculated score is shown next to the colored box. Panel B shows individual patient data of daily angina episodes irrespective of the units of antianginal medication prescribed. Panel C shows the number of units of antianginal medications prescribed for each patient on each day of the trial.

Figure 2. Secondary end points.

Panel A shows treadmill exercise at follow-up stratified by baseline performance, with 95% confidence intervals. ETT denotes exercise treadmill time. Panel B shows the distribution of CCS class according to treatment group at pre-randomization and follow-up. CCS denotes Canadian Cardiovascular Society class. The widths of the confidence intervals have not been adjusted for multiplicity. Thus, the confidence intervals should not be used to reject or not reject treatment effects.