Aortic stenosis and coronary artery disease are often concomitant conditions. Sharing multiple risk factors, it is common to encounter patients with both significant valvular and coronary involvement. According to various registries and studies, 30-60% of patients with severe aortic stenosis present with significant coronary artery disease. 

Currently, the guidelines from the European Society of Cardiology provide a class IIa recommendation and level of evidence A for revascularization of >70% lesions in patients undergoing TAVI, especially if proximal segments are affected, based on findings from clinical trials such as PARTNER 1 and 2 and EXCEL, among others. Recently, the NOTION 3 trial reinforced the idea that clearly significant lesions, whether identified by angiography or functional assessment, should be revascularized to reduce adverse events in these patients. 

Recognizing that significant coronary lesions must be addressed in TAVI candidates with a comorbidity profile or high surgical risk, another challenge arises: timing. 

Traditionally, most PCI procedures were performed prior to valve implantation, driven mainly by the complexity of the approach post-valve implantation or to prevent significant hemodynamic compromise during implantation, especially in proximal or left main lesions. 

The next most common approach is to perform PCI concomitantly with valve implantation, aiming to reduce bleeding complications (avoiding dual antiplatelet therapy during valve implantation), although at the expense of extending procedural time and complexity. 

Finally, and gaining traction, is the option of deferred revascularization post-TAVI, following an improvement in the patient’s hemodynamic reserve and avoiding dual antiplatelet therapy during implantation. 

The available evidence on revascularization timing is limited in both volume and quality, largely derived from observational studies, registries, and sub-analyses, and mostly pertaining to pre-TAVI or concomitant revascularization, with almost no data on post-TAVI revascularization. Sub-analyses on revascularization in aortic stenosis patients from classic studies like SURTAVI and PARTNER 2 suggest no clear benefit in reducing overall mortality or cardiovascular events for patients undergoing PCI prior to valve replacement. This may be due to the leniency in considering coronary lesions significant, including a substantial percentage of moderate lesions. The RE-ACCESS study, aimed at comparing pre- and concomitant revascularization, demonstrated no superiority between the two. Additionally, the REVASC-TAVI registry (n = 1603, international and real-world) compared all three revascularization strategies, with deferred revascularization showing favorable outcomes over the other two approaches despite its lower utilization (only 10% of cases) and a significant reduction in overall mortality. 

As shown, the evidence is sparse and inconclusive, emphasizing the need for studies like the one discussed here: TAVI-PCI (A Randomized Comparison of the Treatment Sequence of Percutaneous Coronary Intervention and Transcatheter Aortic Valve Implantation), which we will now review. 

COMMENTARY: 

The TAVI-PCI study is currently in the recruitment phase. It is a prospective, randomized, international, multicenter trial (over 35 centers in Switzerland, Germany, the Netherlands, Austria, and Italy) with a planned enrollment of 934 patients (with 678 already included by June 2024) eligible for TAVI with significant coronary disease (>70% lesions on angiography). Candidates are randomized to receive PCI within 45 days before (pre-TAVI group) or after the TAVI procedure (post-TAVI group). All patients will receive an Edwards SAPIEN 3® or 3 Ultra® valve. The study is designed to assess whether a delayed (post-TAVI) revascularization strategy is “non-inferior” to an early (pre-TAVI) strategy. The primary endpoint is a composite of all-cause death, myocardial infarction, revascularization, cardiovascular death, or major bleeding (as per VARC-2 criteria). The analysis will be conducted on an intent-to-treat basis. Secondary endpoints include individual components of the primary endpoint at 3 months, 1 year, 2 years, and 5 years, stroke, major vascular complications, NYHA functional class, and quality of life as measured by the Kansas City questionnaire. 

Sub-analyses are planned within this study, focusing on functional assessment of coronary lesions (via FFR and QFR) before and after TAVI, biomarker use (particularly troponin as a prognostic marker), antiplatelet therapy (duration, drugs, etc.), and the characteristics of revascularization procedures. 

Some limitations can already be identified, such as the inclusion of only balloon-expandable valves, associated with less coronary ostia compromise and better coronary access. Furthermore, concomitant PCI is not considered (despite evidence suggesting no clinical difference with pre-TAVI strategy and increased procedural complexity), nor does the analysis initially distinguish between proximal and non-proximal segments. 

The direct comparison of both revascularization strategies has been in demand since TAVI became an established therapeutic option. TAVI-PCI stands as one of the first clinical trials to directly compare early versus late revascularization strategies, also aiming to generate hypotheses regarding the interdependence of these clinical entities and their pathophysiological correlation through secondary endpoints. 

Future studies should analyze not only timing but also valve type (evidence on self-expanding prostheses should be generated) and scenarios such as the presence of a previous bioprosthetic valve (valve-in-valve). We are currently awaiting the results of the FUTURE TAVI registry, which compares the long-term outcomes of all three revascularization strategies. 

Given the characteristics of the current “TAVI population” (elderly, comorbid, and susceptible to complications), decisions on managing valvular and coronary disease should remain individualized and assessed by each center’s Heart Team, considering the need for revascularization and its timing. It must be noted that TAVI, based solely on age criteria, is reserved for inoperable or high-risk patients. Concomitant coronary disease, as highlighted in the NOTION-3 study analysis on this blog, remains a surgical indication for operable patients. 

REFERENCE: 

Stähli BE, Linke A, Westermann D, Van Mieghem NM, Leistner DM, Massberg S, et al.; TAVI PCI Investigators. A randomized comparison of the treatment sequence of percutaneous coronary intervention and transcatheter aortic valve implantation: Rationale and design of the TAVI PCI trial. Am Heart J. 2024 Nov;277:104-113. doi: 10.1016/j.ahj.2024.07.019.