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Meta-Analysis
. 2018 Jan 6;7(1):e008010.
doi: 10.1161/JAHA.117.008010.

Unmeasured Confounders in Observational Studies Comparing Bilateral Versus Single Internal Thoracic Artery for Coronary Artery Bypass Grafting: A Meta-Analysis

Mario Gaudino  1 , Antonino Di Franco  2 , Mohamed Rahouma  2 , Derrick Y Tam  3 , Mario Iannaccone  4 , Saswata Deb  3 , Fabrizio D'Ascenzo  4 , Ahmed A Abouarab  2 , Leonard N Girardi  2 , David P Taggart  5 , Stephen E Fremes  3
Affiliations
Meta-Analysis

Unmeasured Confounders in Observational Studies Comparing Bilateral Versus Single Internal Thoracic Artery for Coronary Artery Bypass Grafting: A Meta-Analysis

Mario Gaudino et al. J Am Heart Assoc. .

Abstract

Background: Observational studies suggest a survival advantage with bilateral single internal thoracic artery (BITA) versus single internal thoracic artery grafting for coronary surgery, whereas this conclusion is not supported by randomized trials. We hypothesized that this inconsistency is attributed to unmeasured confounders intrinsic to observational studies. To test our hypothesis, we performed a meta-analysis of the observational literature comparing BITA and single internal thoracic artery, deriving incident rate ratio for mortality at end of follow-up and at 1 year. We postulated that BITA would not affect 1-year survival based on the natural history of coronary artery bypass occlusion, so that a difference between groups at 1 year could not be attributed to the intervention.

Methods and results: We searched MEDLINE and Pubmed to identify all observational studies comparing the outcome of BITA versus single internal thoracic artery. One-year and long-term mortality for BITA and single internal thoracic artery were compared in the propensity-score-matched (PSM) series, that is, the form of observational evidence less prone to confounders. Thirty-eight observational studies (174 205 total patients) were selected for final comparison. In the 12 propensity-score-matched series (34 019 patients), the mortality reduction for BITA was similar at 1 year and at the end of follow-up (incident rate ratio, 0.70; 95% confidence interval, 0.60-0.82 versus 0.77; 95% confidence interval, 0.70-0.85; P for subgroup difference=0.43).

Conclusions: Unmeasured confounders, rather than biological superiority, may explain the survival advantage of BITA in observational series.

Keywords: bypass graft; myocardial revascularization; surgery.

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Figures

Figure 1
Figure 1
A, Forest plot comparing the effect of the use of BITA vs SITA on end of follow‐up mortality across all the included studies (38 studies; 174 205 patients). B, Cumulative analysis of all the included studies using random‐effect model (38 studies; 174 205 patients). BITA indicates bilateral internal thoracic artery; CI, confidence interval; SITA, single internal thoracic artery. Incident rate ratio (IRR) is used.
Figure 2
Figure 2
Results of the metaregression analyses. Univariate metaregression analysis showed that the effect of BITA was not influenced by age (slope P value=0.625; intercept P value=0.941), sex (slope P value=0.160; intercept P value=0.0002), diabetes mellitus (slope P value=0.730; intercept P value=0.0001), and ejection fraction (slope P value=0.674; intercept P value=0.482). Similarly, multivariate metaregression analysis showed that the effect of BITA was not influenced by age (slope P value=0.270), sex (slope P value=0.412), diabetes mellitus (slope P value=0.848), and ejection fraction (slope P value=0.644) with intercept P value=0.487 (plot not shown). BITA indicates bilateral internal thoracic artery; DM, diabetes mellitus; EF, ejection fraction.
Figure 3
Figure 3
Forest plot comparing the effect of the use of BITA vs SITA on end of follow‐up (top) and 1‐year (bottom) mortality in PSM studies in the general population (12 studies; 34 019 patients). BITA indicates bilateral internal thoracic artery; CI, confidence interval; PSM, propensity‐score matched; SITA, single internal thoracic artery. Incident rate ratio (IRR) is used.
Figure 4
Figure 4
Leave‐one‐out analyisis for 1‐year mortality among PSM studies (12 studies). BITA indicates bilateral internal thoracic artery; CI, confidence interval; PSM, propensity‐score matched; SITA, single internal thoracic artery. Incident rate ratio (IRR) is used.
Figure 5
Figure 5
Publication bias as assessed by funnel plots for all‐cause mortality in the primary analysis. A, All included studies. B, Studies performed in the general population vs studies performed in specific subpopulations. C, Unadjusted studies vs adjusted studies. D, PSM studies vs adjusted non‐PSM studies. E, PSM studies at 1‐year follow‐up vs PSM studies at end of follow‐up. PSM indicates propensity‐score matched.
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Comment in

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