The placebo effect is a well described phenomenon in blinded studies evaluating anti-anginal therapeutics, although its impact on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the impact of placebo on endpoints of symptoms, life-quality and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease.
We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of anti-angina therapeutics. Patients randomized to the placebo-arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tabs/week) between baseline and following placebo. The primary outcome was ETT total duration time. Data were pooled with a random effect model.
Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4,925 patients randomized to placebo. ETT total duration time was significantly improved following placebo as compared to baseline (mean [95% confidence interval]: 29.2 [20.6-37.8] seconds) with evidence of high heterogeneity (I 2 = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (p for interaction=0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity.
A substantial placebo effect was present in angina RCTs across a variety of functional and life-quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics (PROSPERO CRD42019132797).
Copyright © 2021. Published by Elsevier Inc.
About The Expert
Guglielmo Gallone
Luca Baldetti
Filippo Angelini
Andrea Saglietto
Matteo Bellettini
Alessandro Beneduce
Viola Ranotti
Mauro Chiarito
Pier Pasquale Leone
Matteo Pagnesi
Ovidio De Filippo
Federico Landra
Francesco Bruno
Giorgio Marengo
Massimo Collino
Giuseppe Ferrante
Giulio G Stefanini
Antonio Colombo
Rasha Al-Lamee
Darrel P Francis
Marc E Jolicoeur
Timothy D Henry
Francesco Giannini
Fabrizio D’Ascenzo
Gaetano Maria De Ferrari
References
PubMed