Percutaneous coronary intervention (PCI) was originally introduced to treat stable angina.1 More than 500 000 PCI procedures are done annually worldwide for stable angina. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial showed no difference in myocardial infarction and death rates between patients with stable coronary artery disease who underwent PCI and controls.2 Meta-analyses have shown similar results.3
Angina relief remains the primary reason for PCI in stable coronary artery disease.4 Guidelines recommend antianginal medication as first line therapy, with PCI reserved for the many patients who remain symptomatic.5
Data from unblinded randomised trials have shown significant exercise time improvement, angina relief, and quality of life improvement from PCI.6, 7, 8 However, symptomatic responses are subjective and include both a true therapeutic effect and a placebo effect.9 Moreover, in an open trial, if patients randomised to no PCI have an expectation that PCI is advantageous, this might affect their reporting (and their physician's interpretation) of symptoms, artifactually increasing the rate of unplanned revascularisation in the control group.4, 10
Placebo effects are known to be larger for invasive than non-invasive treatments.11 Interventional cardiologists and patients with stable angina often think that PCI offers symptomatic relief.12 Additionally, cardiologists present a decisive approach to diagnosis and treatment, which can lead to an enhanced placebo effect.13 In the absence of blinding, the effect size of PCI on symptomatic endpoints can be overestimated because of the addition of the placebo effect to the true physiological effect of intervention.14 In all previous trials, both investigators and patients were aware of the treatment allocation.2, 8, 10
Research in context
Evidence before this study
More than 500 000 percutaneous coronary interventions (PCIs) are done annually worldwide for the relief of angina but no placebo-controlled trials have been done on the subject. Unblinded PCI is reported to increase exercise time by 96 s more than medical therapy. Single antianginal agents typically increase exercise time by more than 45 s compared with placebo so ORBITA was designed conservatively to detect an effect size of 30 s.
Added value of this study
ORBITA investigated the efficacy of PCI versus placebo to improve exercise capacity in patients with severe coronary disease who were receiving guideline-directed optimum medical therapy. The coronary stenoses were severe and had large haemodynamic effects. Despite PCI markedly improving haemodynamic and imaging indices, PCI did not improve exercise time compared with placebo.
Implications of all the available evidence
The common clinical perception is that patients with stable angina will receive substantial symptom relief from PCI. The results of ORBITA, the only blinded, randomised placebo-controlled trial of PCI, show that even with severe coronary stenosis, exercise capacity and symptoms are not improved significantly compared with a placebo intervention. Physicians advising patients on interventional treatment choices for symptom relief should favour placebo-controlled data. ORBITA shows this approach to be feasible and informative.
Cardiologists have so far been resistant to the idea of a placebo-controlled trial of angina relief from PCI for two main reasons. The first is the widespread perception that PCI unquestionably improves angina,15 a perception that is based on unblinded clinical experience. The second reason is that it might be unethical to expose patients to an invasive placebo procedure. However, no evidence of harm to placebo groups was found in a systematic review of placebo-controlled surgical trials.16
When offering an invasive intervention for symptomatic relief, it is essential to know the true efficacy of the intervention, particularly when the patient could choose to continue conservative treatment instead. Moreover, although PCI has become progressively safer, there remains a complication rate of 1–2%.17
Evidence from placebo-controlled randomised controlled trials shows that single antianginal therapies provide improvements in exercise time of 48–55 s.18, 19 The Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial was designed to assess the effect of PCI versus placebo on exercise time in patients with stable ischaemic symptoms, Given the previous evidence, ORBITA was conservatively designed to be able to detect an effect size of 30 s.