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Meta-Analysis
. 2020 Jul 14;41(27):2556-2569.
doi: 10.1093/eurheartj/ehaa495.

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

Lucas Lauder  1 , Bruno R da Costa  2   3 , Sebastian Ewen  1 , Sean S Scholz  1 , William Wijns  4 , Thomas F Lüscher  5   6 , Patrick W Serruys  7 , Elazer R Edelman  8   9 , Davide Capodanno  10 , Michael Böhm  1 , Peter Jüni  2   11 , Felix Mahfoud  1   9
Affiliations
Meta-Analysis

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

Lucas Lauder et al. Eur Heart J. .

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.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Flow diagram of trial selection (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009).
Figure 2
Figure 2
Risk of bias assessment of all included trials. Risk of bias was assessed according to the revised Cochrane risk of bias tool for randomized trials (RoB2).
Figure 3
Figure 3
Comparison of the treatment effect of active vs. placebo procedures for continuous primary outcomes. Standardized mean differences were standardized, so that positive values indicated a benefit of the active intervention over placebo. LV, left ventricular; PCWP, pulmonary capillary wedge pressure; PTCA + DES, percutaneous transluminal coronary angioplasty and implantation of a drug-eluting stent; SBP, systolic blood pressure.
Figure 4
Figure 4
Comparison of the treatment effect of active vs. placebo procedures for binary primary outcomes. aComposite of death, myocardial infarction, repeat target lesion or percutaneous revascularization, and coronary artery bypass graft. bResponder rate was defined as a blood pressure drop ≥10 mmHg in systolic office blood pressure as a part of a composite outcome. cResponse was defined as an increase in office systolic blood pressure >35 mmHg while the baroreflex activation therapy device was turned off. BP, blood pressure; CCS, Canadian Cardiovascular Society; MACE, major adverse cardiovascular events; PFO, patent foramen oval.
Figure 5
Figure 5
Subgroup analyses by methodological characteristics of trials. Subgroup analyses accompanied by random-effects meta-regression were performed to test for an interaction between treatment effects and methodological characteristics of trials (see Supplementary material online, Methods 2). For these analyses, standardized mean differences were converted to odds ratios.
Take home figure
Take home figure
This systematic review and meta-analysis analyses the comparative efficacy and safety of invasive cardiovascular interventions compared with invasive placebo procedures and the interactions between treatment effects and methodological characteristics.
None
See this image and copyright information in PMC

Comment in

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