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Randomized Controlled Trial
. 2024 Jul 2;84(1):13-24.
doi: 10.1016/j.jacc.2024.04.016. Epub 2024 May 15.

Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease

Florentina A Simader  1 , Christopher A Rajkumar  1 , Michael J Foley  1 , Fiyyaz Ahmed-Jushuf  1 , Shayna Chotai  1 , Nina Bual  2 , Arif Khokhar  2 , Aisha Gohar  2 , Ioannis Lampadakis  3 , Sashiananthan Ganesananthan  1 , Rachel H Pathimagaraj  1 , Alexandra Nowbar  4 , John R Davies  5 , Tom R Keeble  5 , Peter D O'Kane  6 , Peter Haworth  7 , Helen Routledge  8 , Tushar Kotecha  9 , James C Spratt  10 , Rupert Williams  11 , Sukhjinder S Nijjer  1 , Sayan Sen  2 , Nick Curzen  12 , Manas Sinha  13 , James P Howard  1 , Graham Cole  1 , Frank E Harrell Jr  14 , Darrel P Francis  1 , Matthew J Shun-Shin  1 , Rasha K Al-Lamee  15 ; ORBITA-2 Investigators
Collaborators, Affiliations
Free article
Randomized Controlled Trial

Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease

Florentina A Simader et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Placebo-controlled evidence from ORBITA-2 (Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina-2) found that percutaneous coronary intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many patients. The reason for this was unclear.

Objectives: This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, noninvasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI.

Methods: Prerandomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the World Health Organization Rose angina questionnaire (Rose). Disease severity was assessed using quantitative coronary angiography, stress echocardiography, fractional flow reserve, and instantaneous wave-free ratio. Bayesian ordinal regression was used.

Results: At prerandomization, the median number of daily angina episodes was 0.8 (Q1-Q3: 0.4-1.6), 64% had Rose angina, quantitative coronary angiography diameter stenosis was 61% (Q1-Q3: 49%-74%), stress echocardiography score was 1.0 (Q1-Q3: 0.0-2.7), fractional flow reserve was 0.63 (Q1-Q3: 0.49-0.75), and instantaneous wave-free ratio was 0.78 (Q1-Q3: 0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with quantitative coronary angiography ordinal correlation coefficient: 0.06 (95% credible interval [CrI]: 0.00-0.08); stress echocardiography: 0.09 (95% CrI: 0.02-0.10); fractional flow reserve: 0.04 (95% CrI: -0.03 to 0.07); and instantaneous wave-free ratio: 0.04 (95% CrI: -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR: 1.9; 95% CrI: 1.6-2.1; probability of interaction [PrInteraction] = 99.9%; and OR: 1.8; 95% CrI: 1.6-2.1; PrInteraction = 99.9%, respectively).

Conclusions: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI.

Keywords: percutaneous coronary intervention; stable angina; stable coronary artery disease.

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Conflict of interest statement

Funding Support and Author Disclosures ORBITA-2 was an investigator-initiated trial sponsored by Imperial College London. The trial was funded by grants from National Institute for Health and Care Research Imperial Biomedical Research Centre, Medical Research Council, British Heart Foundation, National Institute for Health and Care Research, and the Imperial Coronary Flow Trust. Philips Volcano supplied the coronary pressure wires. Dr Simader has received a sponsorship from Servier Pharmaceuticals. Dr Rajkumar has received speaker fees from Menarini; and has received consulting fees from Philips. Dr Foley has received speaker fees from Menarini and Philips. Dr Khokhar has received speaker fees and travel support from Boston Scientific and Abbott. Dr Davies has received grants from Medtronic and Abbott; has received sponsorship from Vascular Perspectives, Boston Scientific, Medtronic and Abbott; and has received speaker fees from AstraZeneca, Pfizer, Bristol Myers Squibb, and Novartis. Dr Keeble has served on advisory boards for Abbott Vascular and SMT; and has received institutional research funding from Terumo, Medtronic, Boston Scientific, Abbott Vascular, Philips Volcano, and Cardionovum. Dr O’Kane has received speaker fees from Abbott Vascular, Biosensors, Boston Scientific, Heartflow, Medtronic, Philips, Shockwave, and Terumo. Dr Kotecha has received honoraria from Bayer and Janssen. Dr Nijjer has received speaker fees from Philips Volcano, Pfizer, Bayer, AstraZeneca, Boehringer Ingelheim, and Amarin. Dr Spratt has received speaker fees from Boston Scientific Corporation and Shockwave Medical, Inc. Dr Sen has received speaker and consulting fees from Philips, Medtronic, Recor, and AstraZeneca. Dr Curzen has received grants from Beckman Coulter, Inc, Boston Scientific Corporation, Haemonetics Corporation, and HeartFlow Inc; and has received speaker fees from Heartflow. Dr Howard has received shares in Mycardium AI; and has received a grant from the British Heart Foundation. Dr Cole has received shares in Mycardium AI. Dr Al-Lamee has served on advisory boards for Janssen Pharmaceuticals, Abbott, and Philips; and has received speaker fees from Abbott, Philips, Medtronic, Servier, Omniprex, and Menarini. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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