Randomized trials of invasive cardiovascular interventions that include a placebo control: a systematic review and meta-analysis

Lucas Lauder; Bruno R da Costa; Sebastian Ewen; Sean S Scholz; William Wijns; Thomas F Lüscher; Patrick W Serruys; Elazer R Edelman; Davide Capodanno; Michael Böhm; Peter Jüni; Felix Mahfoud

doi:10.1093/eurheartj/ehaa495

Randomized trials of invasive cardiovascular interventions that include a placebo control: a systematic review and meta-analysis

Eur Heart J. 2020 Jul 14;41(27):2556-2569. doi: 10.1093/eurheartj/ehaa495.

Authors

Lucas Lauder¹, Bruno R da Costa^{2

3}, Sebastian Ewen¹, Sean S Scholz¹, William Wijns⁴, Thomas F Lüscher^{5

6}, Patrick W Serruys⁷, Elazer R Edelman^{8

9}, Davide Capodanno¹⁰, Michael Böhm¹, Peter Jüni^{2

11}, Felix Mahfoud^{1

9}

Affiliations

¹ Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Saarland University, Kirrberger Str., Gebäude 41.1, 66421 Homburg/Saar, Germany.
² Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, University of Toronto, 155 College Street, Toronto, ON M5T 3M6, Canada.
³ Institute of Primary Health Care (BIHAM), University of Bern, Mittelstraße 43, 3012 Bern, Switzerland.
⁴ The Lambe Institute for Translational Medicine and CURAM, National University of Ireland, University Road, Galway H91 TK33, Ireland.
⁵ Center for Molecular Cardiology, Schlieren Campus, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland.
⁶ Royal Brompton and Harefield Hospital Trust, Imperial College London, Sydney Street, London SW3 6NP, UK.
⁷ The National Lung and Heart Institute, Imperial College London, Dovehouse St, Chelsea, London SW3 6LY, UK.
⁸ Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
⁹ Institute for Medical Engineering and Science, MIT, 77 Massachusetts Ave., Cambridge, MA 02139, USA.
¹⁰ Division of Cardiology, C.A.S.T., P.O. "G. Rodolico", Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele", University of Catania, Via S. Citelli, 31 Catania, Italy.
¹¹ Department of Medicine, Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, Toronto, ON M5T 3M6, Canada.

Abstract

Aims: The difference in the benefit of invasive cardiovascular interventions compared with placebo controls has not been analysed systematically.

Methods and results: MEDLINE and Web of Science were searched through 29 March 2020. Randomized, placebo-controlled trials of invasive cardiovascular interventions (including catheter-based interventions and pacemaker-like devices) investigating predefined primary outcomes were included. Standardized mean differences (SMD) and odds ratios were calculated for continuous and dichotomous outcomes, respectively. Meta-regression analyses were performed to assess whether estimates of treatment effects were associated with methodological characteristics of trials. Thirty trials, including 4102 patients, were analysed. The overall risk of bias was judged to be low in only 43% of the trials. Ten trials (33%) demonstrated statistically significant superiority of invasive interventions over placebo controls for the respective predefined primary outcomes. In almost half of the 16 trials investigating continuous predefined primary outcomes, the SMD between the active and placebo procedure indicated a small (n = 4) to moderate (n = 3) treatment effect of active treatment over placebo. In contrast, one trial indicated a small treatment effect in favour of the placebo procedure. In the remaining trials, there was no relevant treatment effect of active treatment over placebo. In trials with a protocol-mandated stable and symmetrical use of co-interventions, the superiority of active procedures vs. invasive placebo procedures was significantly larger as compared with trials with frequent or unbalanced changes in co-interventions (P for interaction 0.027).

Conclusions: The additional treatment effect of invasive cardiovascular interventions compared with placebo controls was small in most trials.

Keywords: Heart failure; Percutaneous coronary intervention; Renal denervation; Sham-controlled trials.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Humans
Randomized Controlled Trials as Topic*

Grants and funding

R01 GM049039/GM/NIGMS NIH HHS/United States