Highlights
– In the international, multicentre TCW trial (n=172; mean age 76.5 years), FFR-guided PCI plus TAVI met the prespecified non-inferiority margin versus conventional SAVR plus CABG for a composite 1‑year outcome and was superior (hazard ratio 0.17; 95% CI 0.06–0.51; psuperiority<0.001).
– The superior outcome was driven mainly by lower all‑cause mortality (0% vs 10%; p=0.0025) and reduced life‑threatening or disabling bleeding (2% vs 12%; p=0.010) with the percutaneous strategy.
– These findings challenge the established paradigm that combined SAVR + CABG is uniformly preferred in patients with severe aortic stenosis and complex multivessel coronary disease, suggesting a less invasive approach can be effective in selected patients.
Background and clinical context
Severe aortic stenosis (AS) and concomitant obstructive coronary artery disease (CAD) commonly co-exist, particularly in older adults. Contemporary registries estimate that roughly half of patients with severe AS have obstructive CAD requiring consideration for revascularisation. Current guideline recommendations have generally favored combined surgical aortic valve replacement (SAVR) with coronary artery bypass grafting (CABG) when both pathologies require durable therapy, driven by historical concerns about completeness of revascularisation and durability of valve therapy.
However, the rapid evolution of transcatheter aortic valve implantation (TAVI) and the maturation of physiology-guided percutaneous coronary intervention (PCI) using fractional flow reserve (FFR) have created a plausible percutaneous pathway: TAVI to treat the valve, and FFR-guided PCI to target ischaemia-producing lesions selectively. Prior trials have shown clinical equipoise or superiority of TAVI over SAVR in selected surgical‑risk populations (for example PARTNER 3, Evolut Low Risk), and FFR-guided PCI reduced ischemic events compared with angiography‑guided approaches in multivessel disease (FAME, FAME‑2). Yet, until the TCW trial, no randomized evidence had compared a combined percutaneous strategy to standard combined cardiac surgery in patients with both severe AS and complex or multivessel CAD.
Study design and interventions
TCW was an international, multicentre, prospective, open‑label, non‑inferiority randomized controlled trial conducted at 18 tertiary centres across Europe. Patients aged ≥70 years with severe aortic stenosis and complex or multivessel coronary artery disease who were considered feasible for either percutaneous or surgical treatment by the on‑site Heart Team were eligible. Randomization was 1:1 to either:
- FFR-guided PCI plus TAVI, or
- SAVR plus CABG.
Randomisation used computer-generated random permuted blocks stratified by site. The primary endpoint was a composite at 1 year of all‑cause mortality, myocardial infarction, disabling stroke, clinically driven target‑vessel revascularisation, valve reintervention, and life‑threatening or disabling bleeding. The study was powered for non‑inferiority using a prespecified 15% margin, with a hierarchical plan to test for superiority if non‑inferiority was met. Primary and safety analyses were performed on an intention‑to‑treat basis. The trial was registered on ClinicalTrials.gov (NCT03424941).
Key findings
Between May 31, 2018 and June 30, 2023, 172 patients were randomized: 91 to FFR-guided PCI + TAVI and 81 to SAVR + CABG. Mean patient age was 76.5 years (SD 3.9); 69% were male. The trial reported the following primary outcome results at 1 year:
- Primary composite endpoint: 4 of 91 patients (4%) in the FFR‑guided PCI + TAVI arm versus 17 of 77 patients (23%) in the SAVR + CABG arm (risk difference −18.5%; 90% CI −27.8 to −9.7). The result satisfied the prespecified non‑inferiority margin (pnon‑inferiority <0.001) and met criteria for superiority (hazard ratio 0.17; 95% CI 0.06–0.51; psuperiority <0.001).
- All‑cause mortality: 0 of 91 patients (0%) versus 7 of 77 patients (10%) in the SAVR + CABG group (p=0.0025).
- Life‑threatening or disabling bleeding: 2% (2/91) versus 12% (9/77) (p=0.010).
The composite superiority signal was driven mainly by the reductions in mortality and catastrophic bleeding with the less invasive approach. The reporting shows a small number of events overall, but the relative reductions were large and statistically significant. Other components of the composite such as myocardial infarction, disabling stroke, valve reintervention, and target‑vessel revascularisation were not reported here as individually dominant contributors to the composite outcome.
Safety and secondary observations
Perioperative morbidity of cardiac surgery is influenced by cardiopulmonary bypass, anticoagulation, and surgical trauma; bleeding and operative mortality remain important risks, particularly in older patients with comorbidity. The TCW results reflect these differences: the SAVR + CABG group had a higher rate of life‑threatening or disabling bleeding and higher 1‑year mortality. No deaths occurred in the TAVI + PCI arm within 1 year, which is an important safety signal although the absolute numbers are small.
Open‑label design and the pragmatic inclusion of patients judged feasible for either strategy introduce some real‑world heterogeneity but increase applicability to contemporary practice. Details such as procedural success rates, vascular complications, pacemaker implantation, acute kidney injury, length of stay, and quality‑of‑life outcomes will be important to contextualize the clinical implications (and should be sought in the full manuscript and supplementary materials).
Interpretation and mechanistic considerations
Why might the percutaneous strategy perform better at 1 year? Plausible mechanisms include avoidance of sternotomy and cardiopulmonary bypass-related systemic inflammation and organ injury; lower bleeding risk due to less invasive access and shorter exposure to anticoagulation; and tailored revascularisation using FFR to treat only lesions causing ischemia, potentially avoiding unnecessary stenting and associated complications. TAVI has become an established, durable treatment for older patients with severe AS, and in many centres procedural expertise is high. When combined with physiology‑guided PCI, a targeted, staged percutaneous pathway may therefore offer equivalent or superior early outcomes in selected patients.
Limitations and considerations for generalizability
While the TCW trial provides the first randomized comparison between the two strategies, several caveats are important:
- Sample size and event counts are modest. Although statistical thresholds for non‑inferiority and superiority were met, the absolute number of events—particularly deaths—was small and requires confirmation in larger cohorts and longer follow‑up.
- Selection bias: patients were included only if the Heart Team judged them feasible for either approach. This excludes patients with anatomic or surgical contraindications to one strategy and limits generalizability to an ‘equipoise’ population rather than all-comer severe AS with CAD.
- Open‑label design could influence periprocedural management and clinical decision‑making, although hard endpoints such as mortality and life‑threatening bleeding are less susceptible to observer bias.
- Device and operator‑related factors: centres with high TAVI and complex PCI experience may achieve better outcomes than less experienced sites; results may not generalize to centres lacking hybrid capabilities.
- Funding by Medtronic and institutional support from Isala Heart Centre are disclosed; while not diminishing the reported data, potential conflicts warrant transparent independent appraisal and replication.
How this fits with existing evidence and guidelines
Major valve guidelines (e.g., 2021 ESC/EACTS Guidelines for the management of valvular heart disease) traditionally favor SAVR + CABG when both procedures are indicated, particularly when durable surgical revascularisation is required. However, recent TAVI trials (PARTNER 3, Evolut Low Risk) and extensive PCI physiology literature (FAME trials) have shifted the therapeutic landscape. TCW provides randomized evidence that, in selected older patients with complex coronary disease who are Heart Team–selected as suitable for both strategies, a percutaneous pathway can yield superior 1‑year outcomes.
Clinical implications and recommendations
TCW supports consideration of FFR‑guided PCI plus TAVI as a viable—and potentially preferable—strategy in selected patients aged ≥70 years with severe AS and complex CAD who are suitable for either approach. Until confirmatory data and longer follow‑up are available, clinicians should:
- Employ Heart Team deliberation to individualize treatment, incorporating patient preferences, frailty, coronary anatomy, and local expertise.
- Consider FFR to guide revascularisation decisions in patients undergoing TAVI to target ischemia‑producing lesions and potentially limit unnecessary stenting.
- Counsel patients about the trade‑offs: less invasiveness and lower early mortality/bleeding versus unanswered questions about long‑term valve durability, graft patency, and late events.
Future research
Key remaining questions include longer‑term comparative durability of the two strategies (beyond 1 year), subgroup analyses by coronary disease complexity and left main disease, cost‑effectiveness, and replication in broader populations and healthcare settings. Larger randomized trials or pooled meta-analyses with extended follow‑up will be important to fully redefine guideline recommendations.
Funding and trial registration
The TCW trial was funded by Isala Heart Centre and Medtronic. ClinicalTrials.gov registration: NCT03424941.
Selected references
Key references for context (selected, not exhaustive):
- Kedhi E, Hermanides RS, Dambrink JE, et al; TCW study group. TransCatheter aortic valve implantation and fractional flow reserve‑guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and complex or multivessel coronary disease (TCW): Lancet. 2025 Dec 21;404(10471):2593-2602. doi:10.1016/S0140-6736(24)02100-7.
- Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2014;35(37):2541–2619. (Guideline context for revascularisation strategy.)
- Nishimura RA, Otto CM, Bonow RO, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2021;42(5):489–588.
- Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding PCI. N Engl J Med. 2009;360:213–224. (FAME trial)
- De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve–guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367:991–1001. (FAME‑2)
- Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic‑valve replacement with a balloon‑expandable valve in low‑risk patients. N Engl J Med. 2019;380:1695–1705. (PARTNER 3)
- Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter aortic‑valve replacement with a self‑expanding valve in low‑risk patients. N Engl J Med. 2019;380:1706–1715. (Evolut Low Risk)
Concluding summary
The TCW randomized trial is a practice‑changing piece of evidence that, in an older Heart Team–selected population with severe aortic stenosis and complex coronary disease, FFR‑guided PCI plus TAVI achieved non‑inferiority and statistical superiority over SAVR plus CABG at 1 year—largely through reductions in mortality and life‑threatening bleeding. These findings support broader consideration of a percutaneous strategy in selected patients and mandate further confirmatory research with longer follow‑up and expanded populations to inform guideline revisions and clinical practice.
