Angina in stable ischaemic heart disease

The placebo effect describes the natural human tendency to react positively to a healer. As the first placebo-controlled trial of percutaneous coronary intervention (PCI), the ORBITA (Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina) trial was ground-breaking. After decades of routine use, ORBITA showed that PCI offered no significant angina relief compared to placebo on a background of maximally tolerated antianginal medications. Despite this finding, guidelines continue to recommend PCI as an additional therapy for persistent angina refractory to antianginal medication. ORBITA left cardiologists with many questions. Central to the future of PCI as a treatment for angina was the question of whether PCI was simply ineffective, or whether the guideline directed antianginal medication used in ORBITA had attenuated all the observable benefit of PCI. I led the delivery of the ORBITA-2 Trial; designed to answer this question. ORBITA-2 was a randomised, double-blind, placebo-controlled trial in patients with stable angina. To determine the unattenuated efficacy of PCI for angina relief, it was designed with the critical step of removing background antianginal medical therapy. ORBITA-2 shows that PCI, under double-blind placebo-controlled conditions, without background antianginal medications, gives clear benefit across multiple endpoints: angina, quality of life and treadmill exercise time. The benefit is immediate and sustained, although not all symptoms are eliminated. In this thesis, I present the primary and secondary results of the ORBITA-2 Trial. In addition, I present a systematic review and meta-regression of all placebo-controlled trials of procedural therapies, designed to determine for which endpoints blinding matters most. Finally, I present the results of the n-of-1 placebo-controlled ORBITA-STAR trial which tested whether independent symptom verification using anot at al placebo-controlled ischaemic stimulus could distinguish which patients achieve symptom relief from PCI.