Risk of Bias in Randomized Clinical Trials Comparing Transcatheter and Surgical Aortic Valve Replacement
Authors: Barili Fabio , Brophy James M. , Ronco Daniele , Myers Patrick O. , Uva Miguel Sousa , Almeida Rui M. S. , Marin-Cuartas Mateo , Anselmi Amedeo , Tomasi Jacques , Verhoye Jean-Philippe , Musumeci Francesco , Mandrola John , Kaul Sanjay , Papatheodorou Stefania , Parolari Alessandro ,   International Evidence Grading Research Initiative Targeting Transparency and Quality (INTEGRITTY), De Caterina Raffaele , Sadaba Rafael , Misfeld Martin , Milojevic Milan , Boden William , Albuquerque Arthur , Gomes Walter , Dayan Victor , García-Villarreal Ovidio A. , Rodriguez-Roda Stuart Jorge 
Published: January 2023

Importance

Recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines highlighted some concerns about the randomized clinical trials (RCTs) comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for aortic stenosis. Quantification of these biases has not been previously performed.

Objective

To assess whether randomization protects RCTs comparing TAVI and SAVR from biases other than nonrandom allocation.

Data Sources

A systematic review of the literature between January 1, 2007, and June 6, 2022, on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials was performed. Specialist websites were also checked for unpublished data.

Study Selection

The study included RCTs with random allocation to TAVI or SAVR with a maximum 5-year follow-up.

Data Extraction and Synthesis

Data extraction was performed by 2 independent investigators following the PRISMA guidelines. A random-effects meta-analysis was used for quantifying pooled rates and differential rates between treatments of deviation from random assigned treatment (DAT), loss to follow-up, and receipt of additional treatments.

Main Outcomes and Measures

The primary outcomes were the proportion of DAT, loss to follow-up, and patients who were provided additional treatments and myocardial revascularization, together with their ratio between treatments. The measures were the pooled overall proportion of the primary outcomes and the risk ratio (RR) in the TAVI vs SAVR groups.

Results

The search identified 8 eligible trials including 8849 participants randomly assigned to undergo TAVI (n = 4458) or SAVR (n = 4391). The pooled proportion of DAT among the sample was 4.2% (95% CI, 3.0%-5.6%), favoring TAVI (pooled RR vs SAVR, 0.16; 95% CI, 0.08-0.36; P &amp;lt; .001). The pooled proportion of loss to follow-up was 4.8% (95% CI, 2.7%-7.3%). Meta-regression showed a significant association between the proportion of participants lost to follow-up and follow-up time (slope, 0.042; 95% CI, 0.017-0.066; P &amp;lt; .001). There was an imbalance of loss to follow-up favoring TAVI (RR, 0.39; 95% CI, 0.28-0.55; P &amp;lt; .001). The pooled proportion of patients who had additional procedures was 10.4% (95% CI, 4.4%-18.5%): 4.6% (95% CI, 1.5%-9.3%) in the TAVI group and 16.5% (95% CI, 7.5%-28.1%) in the SAVR group (RR, 0.27; 95% CI, 0.15-0.50; P &amp;lt; .001). The imbalance between groups also favored TAVI for additional myocardial revascularization (RR, 0.40; 95% CI, 0.24-0.68; P &amp;lt; .001).

Conclusions and Relevance

This study suggests that, in RCTs comparing TAVI vs SAVR, there are substantial proportions of DAT, loss to follow-up, and additional procedures together with systematic selective imbalance in the same direction characterized by significantly lower proportions of patients undergoing TAVI that might affect internal validity.