Sham-controlled PCI trial does not show symptom relief in stable angina patients
Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial
Over 500 000 PCIs per year are done globally for stable angina, although there are data showing that patients with stable CAD have similar MI and death rates with or without PCI [1,2]. The main reason for PCI in stable CAD is to treat angina and prolong exercise time. This objective is, however, also achievable with antianginal drug therapy, and in addition, PCI is associated with a complication rate of 1-2% [3-5].
The multicenter, randomized ORBITA trial assessed the effect of PCI versus placebo on exercise time in 200 patients with stable ischemic symptoms. Eligible patients had angina or equivalent symptoms and at least one angiographically significant lesion (≥70%) in a single vessel that was clinically appropriate for PCI. Patients with ACS, a stenosis in a non-target-vessel or in the left main stem coronary artery or a chronic total coronary occlusion, as well as patients with a history of CABG, contraindications to DES, severe valvular disease, severe LV systolic impairment, moderate-to-severe pulmonary hypertension, life expectancy less than 2 years, and inability to give consent, were excluded from the study.
After a 6-week medical optimization phase focused guideline directed antianginal therapy, eligible patients underwent pre-randomization assessment, including of the burden of angina symptoms and functional capacity, evaluation of myocardial ischemic burden, and evaluation of quality of life. All patients underwent a research invasive physiological assessment of fractional flow reserve (FFR). After administration of intracoronary nitrate, a pressure wire was placed. The clinical operator was informed of signal quality but not of the physiology values. After sedation, patients were randomized 1:1 to undergo PCI or the placebo procedure. For patients allocated to PCI, DES were used to treat all angiographically significant lesions until complete revascularization was achieved. Patients in the placebo group were kept sedated a for at least 15 minutes on the catheter laboratory table and the catheters were withdrawn without an intervention having been done. 6 weeks post-randomization, there was a follow-up assessment, using the same procedures as in the pre-randomization assessment.
The pre-specified primary endpoint was the difference in exercise time increment between the groups. The objective was to detect an effect size of 30 s. Secondary endpoints were change in peak VO2, change in exercise time to 1 mm ST segment depression, angina severity, physical limitation, angina stability, and angina frequency, QoL (EQ-5D-5L questionnaire), the Duke Treadmill score, and changes in dobutamine stress echocardiography wall motion score index.
- At follow-up, no significant difference was seen between groups in increment in exercise time (16.6; 95% CI: –8.9 to 42.0; P=0.200), nor in peak VO2 uptake change (-12.9 mL/min; 95% CI: -90.2 to 64.3; P=0.741), or in the change in time to 1 mm ST depression (pre-randomization: PCI 479.7±141.4 vs. placebo 471.1±128.7; follow-up: PCI 472.7±129.1 vs. placebo 470.1±176.0; P=0.164).
- There was no significant difference between groups in the proportion of patients with improvements in angina grade from enrolment to pre-randomization (no change: PCI 60% vs. placebo 62%; 1 class improvement: PCI 26% vs. 23%; ≥ 2 class improvement: PCI 14% vs. 15%; P=0.916), and from pre-randomization to follow-up (no change: PCI 49% vs. 55%; 1 class improvement: PCI 26% vs. 24%; ≥ 2 class improvement: PCI 26% vs. 21%; P=0.633).
- During the randomized blinded period there were no significant differences between groups in the change from pre-randomization to follow-up in Seattle physical limitation score (2.4; 95% CI: -3.5 to 8.3; P=0.420), Seattle angina frequency (4.4; 95% CI: -3.3 to 12.0; P=0.260), and Seattle angina stability score (0.9; 95% CI: –8.4 to 10.2; P=0.851).
- There was also no significant difference between the groups in QoL (change in EQ-5D-5L: 0.00; 95% CI: -0.04 to 0.04; P=0.994).
- The change in the Duke treadmill score did not significantly differ between groups (1.12; 95% CI: -0.23 to 2.47; P=0.104).
- The dobutamine stress echocardiography peak stress wall motion score index improved more with PCI than with placebo (-0.09; 95% CI: -0.15 to -0.04; P=0.0011).
- There were 3 peri-procedural major bleeding events, of which 2 were in the PCI group. 4 patients in the placebo group needed PCI for a pressure-wire related complication. During the follow-up phase, in the placebo group, 1 patient developed an ACS, and 2 patients on dual antiplatelet therapy suffered a major bleeding.
In this first blinded, placebo-controlled, randomized trial of PCI in 200 patients with stable angina and 1-vessel-disease (severe coronary stenosis, both anatomically and haemodynamically), PCI did not result in significant short-term improvements of exercise capacity, symptoms and quality of life as compared with a placebo procedure. PCI did yield objective relief of anatomical stenosis, invasive pressure and non-invasive perfusion indices. These data suggest that the physical effects of PCI may be overestimated and confused with placebo effects in clinical practice. These data suggest that PCI might not be essential for symptomatic improvement of these patients in the short-term.