Outcomes of Transcatheter or Surgical Treatment of Severe Aortic Stenosis in Patients With Coronary Artery Disease

Highlights

• •Outcomes of surgical aortic valve replacement + coronary artery bypass grafting vs. transcatheter aortic valve replacement (TAVR) + percutaneous coronary intervention (PCI) in severe aortic stenosis and coronary artery disease patients.
• •TAVR + PCI had lower 30-day acute kidney injury and bleeding, similar 2-year mortality/stroke.
• •PCI timing (pre-, peri-, and post-TAVR) did not impact long-term clinical outcomes.
• •Results support TAVR + PCI as a viable option in select high-risk patients.

Transcatheter aortic valve replacement (TAVR) has shown comparable outcomes to surgical aortic valve replacement (SAVR) across all risk categories in many pivotal randomized controlled trials. Many of these trials excluded patients needing myocardial revascularization. However, it is essential to recognize that significant coronary artery disease (CAD) commonly coexists with degenerative severe aortic stenosis (AS), affecting approximately 50% of patients.¹ Current guidelines recommend a combined procedure of SAVR and coronary artery bypass grafting (CABG) in these patients.² Nevertheless, common clinical practice frequently involves performing percutaneous coronary intervention (PCI) either before, simultaneously, or after TAVR. We aimed to evaluate and compare 2-year clinical outcomes among patients with severe AS and significant CAD treated either with TAVR accompanied by staged or simultaneous PCI or with concomitant SAVR and CABG.

We conducted a retrospective cohort analysis of de-identified, aggregate patient data from the TriNetX research network, which contains data from the electronic health records of approximately 115 million patients from 72 health care organizations, primarily in the United States. Patients aged ≥18 years with a diagnosis of severe AS stenosis and stable significant CAD (at least 50% stenosis in any major epicardial vessel) between January 2012 and January 2022 were identified. Patients were then divided into two groups based on whether they underwent TAVR + PCI or SAVR + CABG. Baseline characteristics of the groups were compared. Primary and secondary outcomes (defined by International Classification of Diseases, Tenth Revision codes) were analyzed over a 2-year follow-up period. The primary outcome was a composite of all-cause mortality and stroke. Secondary outcomes included 30-day permanent pacemaker implantation, acute kidney injury, and procedure-related hemorrhage (with or without transfusion). Covariates (notably baseline characteristics, prevalence of 3-vessel disease and left main disease, comorbidities, medications, left ventricular ejection fraction [LVEF], and baseline hemoglobin and serum creatinine) were matched extensively by 1:1 propensity score matching using the greedy nearest-neighbor algorithm with a caliper of 0.1 pooled standardized mean difference (SMD). Any characteristic with a SMD between cohorts lower than 0.1 was considered well-matched. The measures of association included odds ratios (ORs) on the matched population for primary and secondary outcomes. Survival analyses were performed for each outcome by plotting Kaplan-Meier curves with log-rank tests; additionally, Cox proportional hazard models were used to calculate the hazard ratio to compare the 2 groups. Death was considered a censoring event. A value of p < 0.05 was considered statistically significant. Analyses were completed using the TriNetX online platform using R for statistical computing. The study was exempt from institutional review board/ethics committee approval as it leveraged a de-identified database. Data were analyzed and interpreted by the authors. All authors reviewed the manuscript and affirmed the accuracy and completeness of the data.

A total of 16,592 patients were included, of which 1626 (9.8%) underwent TAVR + PCI and 14,966 (90.2%) underwent SAVR + CABG. Those who underwent TAVR + PCI were older (79.2 ± 8.1 vs. 70.7 ± 9.2 years; p < 0.0001) and had a higher prevalence of chronic kidney disease (44.6 vs. 19.4%; p < 0.0001), atrial fibrillation (19.2 vs. 9.6%; p < 0.0001), history of stroke (6.9 vs. 5.1%; p = 0.002), lower LVEF (52.1 vs. 55.3%; p < 0.0001), and lower prevalence of 3-vessel/left main disease (18 vs. 29%; p < 0.0001) compared with those who underwent SAVR + CABG. All PCIs were performed either concomitantly (28.1%) or within 3 months before (49.1%) or after TAVR (22.8%). During follow-up, the composite primary outcome of death or stroke was observed in 27.8% of patients in the TAVR + PCI group and 16.2% of patients in the SAVR + CABG group. Subsequently, the matched cohort included 2110 patients (1055 per group; mean age: 77.1 years; 31% female; 81% White; mean LVEF: 53.5%). No residual imbalances were found (SMD: <0.1 for all covariates). In that cohort, the primary outcome was comparable between the two groups (OR: 1.202 [95% CI: 0.99-1.46]; p = 0.065). Both groups had similar 30-day rates of permanent pacemaker implantation (OR: 0.672 [95% CI: 0.37-1.49]; p = 0.18). However, TAVR + PCI was associated with a lower risk of acute kidney injury (OR: 0.434 [95% CI: 0.33-0.57]; p < 0.001) and procedure-related hemorrhage (OR: 0.182 [95% CI: 0.11-0.29]; p < 0.001) at 30 days. Time-to-event analysis of the primary outcome is depicted in Figure 1. In subgroup analysis of patients, outcomes in the TAVR group were similar regardless of PCI timing.

Figure 1.

Time-to-event analysis of the primary outcome in the matched cohort CABG, HR, PCI, SAVR, and TAVR

Kaplan-Meier survival curves comparing cumulative incidence of the composite outcome of all-cause mortality or stroke between patients undergoing TAVR + PCI versus SAVR + CABG. After 1:1 propensity score matching, no statistically significant difference in event-free survival was observed over 2 years (log-rank p = 0.264; matched HR: 1.101 [95% CI: 0.93-1.30]). Abbreviations: CABG, coronary artery bypass grafting; HR, hazard ratio; PCI, percutaneous coronary intervention; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement.

In patients with severe AS and CAD, the combined surgical approach of SAVR + CABG has traditionally been regarded as the standard of care, offering comprehensive treatment and favorable long-term outcomes.³ However, growing evidence suggests that less invasive strategies may offer comparable clinical efficacy. In this present study, patients who underwent TAVR + PCI were older and had a higher burden of comorbidities than those who underwent SAVR + CABG, which most likely explains the worse outcomes in the unadjusted analysis. Yet, after tight propensity score matching to account for potential confounders, clinical outcomes at 2 years were comparable between the two groups. In contrast to our study, a recent study with a 1-year follow-up of 1342 patients reported that patients undergoing TAVR with PCI experienced fewer complications, including mortality and stroke, compared to those treated with SAVR and CABG.⁴ We believe that the conclusion suggesting superior outcomes with one approach compared to the other may be confounded by inherent differences in patient populations, such as baseline comorbidities, surgical risk profiles, and anatomical extent of CAD, despite rigorous statistical adjustments for confounding variables. Rather, we aim to demonstrate that, when patients are carefully selected by a multidisciplinary heart team, particularly those at high surgical risk, TAVR + PCI represents a valuable therapeutic option with favorable surgical-like clinical outcomes. The recently published transcatheter valve and vessels trial, which compared TAVR with fractional flow reserve-guided PCI (n = 91) to SAVR with CABG (n = 81) in patients with severe AS and complex CAD, demonstrated lower all-cause mortality and life-threatening bleeding at 1 year in the TAVR + PCI group. While our findings similarly showed reduced bleeding complications, mortality was comparable between groups at 2 years in our cohort. Differences in patient age, sample size, and follow-up duration may limit direct comparisons. In the transcatheter valve and vessels trial, the SAVR + CABG group had a mean age of 77 years, with 21% of patients older than 80, a total cohort size of 171 patients, and a follow-up of 1 year.⁵ Our study adds to the literature by providing a larger and younger cohort with longer follow-up.

Limitations

Data for this study were obtained from an aggregate electronic health record database (TriNetX). As such, the accuracy of reported health conditions and the completeness of captured outcomes occurring outside of the database may be limited. Additionally, Society of Thoracic Surgeons risk scores were unavailable for analysis and direct adjustment. However, we attempted to mitigate this limitation by including all variables used in the Society of Thoracic Surgeons operative risk calculator within our matched propensity score model. Moreover, the detailed anatomical extent of CAD beyond prevalence of left main disease and 3-vessel disease was not explicitly reported, nor was the extension of revascularization (complete/incomplete). Hence, despite robust propensity matching, potential selection bias from unmeasured confounding factors remains a limitation. Nevertheless, we believe this study provides valuable insights into the outcomes of TAVR + PCI and SAVR + CABG in patients with severe AS and CAD. Further prospective randomized studies are warranted to validate our findings.

Review Statement

The review of this manuscript was managed by Guest Editor Laurent Faroux, MD, PhD.

Funding

The authors have no funding to report. The study was conducted in adherence to research ethical guidelines with appropriate Institutional Review Board exemption from Institutional Review Board committee approval.

Disclosure Statement

The authors report no conflict of interest.

Guest Editor: Laurent Faroux, MD, PhD