PCI Before TAVI (Coronary Revascularisation in TAVI Candidates)

Definition

The question of whether to perform percutaneous coronary intervention (PCI) for concomitant stable coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. CAD is present in ~50% of TAVI candidates; between 10–20% currently receive PCI. Prior to 2024, no large RCT had established a benefit for this strategy.

Key Concepts

Epidemiology and Clinical Context

• ~50% of patients undergoing TAVI have concomitant CAD (anatomic or physiological) sources/PCI-TAVI-NOTION3-NEJM-2024 very high
• 10–20% of TAVI recipients currently receive PCI; uncertain whether this improves outcomes or simply adds procedural risk
• Stable CAD found incidentally during TAVI workup may be a "bystander" for which PCI risks outweigh benefits — or may represent a treatable residual risk
• Aortic stenosis and CAD share risk factors (ageing, dyslipidaemia, hypertension, smoking); their co-occurrence is expected and not coincidental

Guideline Recommendations (ESC 2025)

• Class IIa B: PCI for ≥90% diameter stenosis in vessels ≥2.5 mm before TAVI (directly citing NOTION-3) sources/PCI-TAVI-NOTION3-NEJM-2024 very high
• Class IIb B: PCI for ≥70% stenosis in proximal segments of main vessels before any transcatheter valve intervention
• CCTA is sufficient to rule out significant CAD if the procedural CT is of sufficient quality (new Class IIa)
• Consider coronary access post-TAVI: valve frame height, commissural alignment, narrow aortic root may limit future coronary access

NOTION-3 Trial (NEJM 2024) — The Key Evidence

• International, open-label, randomized superiority trial; n=455; 12 Nordic-Baltic sites; September 2017–October 2022; median 2-year follow-up sources/PCI-TAVI-NOTION3-NEJM-2024 very high
• Inclusion: Severe symptomatic AS + ≥1 coronary stenosis with FFR ≤0.80 or ≥90% diameter stenosis in vessel ≥2.5 mm
• Exclusion: ACS ≤14 days, eGFR <20, left main disease, valve-in-valve TAVI, life expectancy <1 year
• Population: Median age 82; 67% male; STS-PROM 3%; SYNTAX score 9 (low complexity); contemporary population
• Primary endpoint — MACE (death/MI/urgent revascularisation): PCI 26% vs conservative 36%; HR 0.71 (95% CI 0.51–0.99; P=0.04)
• Mortality: All-cause death HR 0.85 (NS) — no significant mortality benefit
• MI: HR 0.54 (95% CI 0.30–0.97) — significant reduction
• Urgent revascularisation: HR 0.20 (95% CI 0.08–0.51) — significant reduction
• Bleeding: PCI 28% vs conservative 20%; HR 1.51 (95% CI 1.03–2.22) — significantly more bleeding with PCI
• Acute kidney failure: PCI 5% vs conservative 11%; HR 0.45 — significantly less AKI with PCI
• Complete revascularisation achieved in 89% of PCI group; 89% revascularised before TAVI (strongly recommended by protocol)

ACTIVATION Trial (JACC:CI 2021) — The Prior Evidence

• Randomized trial; n=235; UK centres; 1-year follow-up
• CAD defined anatomically (≥70% diameter stenosis) — less reliable than FFR for physiological significance
• Required CCS angina class <3 — selected lower-symptom patients
• Result: Did not meet non-inferiority of conservative treatment; stopped early for futility — inconclusive
• Key differences from NOTION-3: smaller sample, shorter follow-up, anatomic (not FFR) CAD selection, older era

FFR in the Context of Aortic Stenosis

• FFR may underestimate physiological significance of coronary stenosis in patients with severe AS — AS increases microvascular resistance, which reduces the pressure gradient across stenoses
• However, the clinical magnitude of this underestimation is limited: FFR values cross the 0.80 cutoff in only ~10% of patients when measured before vs 6 months after TAVI
• FFR in TAVI patients still predicts outcomes — its reliability is diminished but not eliminated
• iFR (instantaneous wave-free ratio) is suggested to be less reliable than FFR in severe AS — not recommended as the primary physiological index in this population
• Whether CAD assessment should prioritise physiological (FFR) vs anatomic (visual angiography) assessment remains an open question — the ongoing FAITAVI trial (physiology-guided vs angiography-guided PCI in TAVI) is addressing this

Antithrombotic Implications of PCI + TAVI

• PCI group in NOTION-3: aspirin lifelong + clopidogrel 75 mg × 6 months; OAC patients received shortened aspirin (7 days, per AUGUSTUS 2019) + clopidogrel 6 months + lifelong OAC
• Conservative group evolved to aspirin monotherapy (per POPular TAVI 2020)
• DAPT required for PCI partially explains higher bleeding rates in the PCI group
• The net clinical benefit must weigh MACE reduction (HR 0.71) against bleeding excess (HR 1.51) on an individual patient basis

Timing of PCI Relative to TAVI

• NOTION-3 protocol: PCI strongly recommended before TAVI as a staged procedure
• PCI performed concomitantly with or ≤2 days post-TAVI in 26% of PCI patients — acceptable per protocol
• Optimal timing (pre- vs peri- vs post-TAVI) has not been definitively established by any RCT
• Mechanical advantage of pre-TAVI PCI: avoids competitive interaction with the valve delivery system; allows verification of successful PCI before committing to valve implantation
• Post-TAVI coronary access may be limited by the implanted valve (frame height, commissural alignment)

Patient Selection for PCI

• NOTION-3 results should be interpreted in context of its population: low SYNTAX score (median 9), few patients with multivessel disease
• Decision to perform PCI should be individualised, weighing:
  • Patient age, overall health, life expectancy
  • Complexity and severity of CAD (SYNTAX score, multivessel involvement)
  • Bleeding risk
  • Feasibility of future coronary access post-TAVI
  • Patient preference
• Patients with higher SYNTAX scores, left main disease, or recent ACS were excluded — no extrapolation to these groups

Contradictions / Open Questions

• Mortality neutral despite MACE benefit: All-cause death was HR 0.85 (NS) despite composite MACE reduction (HR 0.71; P=0.04). Urgent revascularisation reduction (HR 0.20) is the dominant driver of the primary endpoint result. Whether this represents a genuine reduction in hard clinical events or partly reflects open-label knowledge of untreated lesions in the conservative arm (driving unplanned hospitalisations) is debated. sources/PCI-TAVI-NOTION3-NEJM-2024 very high

• Bleeding excess vs MACE benefit — individualized net effect: PCI increased bleeding (HR 1.51; 95% CI 1.03–2.22) alongside reducing MACE (HR 0.71). In an elderly, frail population (median age 82), serious bleeding events carry high morbidity and mortality. The net clinical benefit requires individual risk-benefit analysis that may differ substantially across patients. sources/PCI-TAVI-NOTION3-NEJM-2024 very high

• FFR reliability in severe AS: FFR systematically underestimates coronary stenosis severity in severe AS due to increased microvascular resistance. The 0.80 threshold, validated in non-AS populations, may not be optimal here. Whether a stricter cutoff (e.g., ≤0.75) would better identify TAVI patients who benefit from PCI remains unknown. sources/PCI-TAVI-NOTION3-NEJM-2024 very high

• ACTIVATION vs NOTION-3 discordance: ACTIVATION (n=235; anatomic ≥70% stenosis; 1 year; inconclusive) was neutral; NOTION-3 (n=455; FFR ≤0.80 or ≥90%; 2 years; positive). The most plausible explanations are: (1) FFR selection identifies truly flow-limiting lesions more precisely than anatomic criteria; (2) longer follow-up captures late ischemic events; (3) the larger, more contemporary population in NOTION-3. These are not mutually exclusive. sources/PCI-TAVI-NOTION3-NEJM-2024 very high

• Optimal PCI timing — pre vs concomitant vs post-TAVI: NOTION-3 recommended pre-TAVI staged PCI but allowed peri/post-TAVI PCI in 26% without apparent detriment. No RCT has directly compared timing strategies. Post-TAVI coronary access limitations with current-generation valves (high frame, non-commissural alignment) make pre-TAVI PCI intuitively preferable for complex anatomy.

• Generalisability to higher SYNTAX scores and left main disease: NOTION-3 population had low CAD complexity (median SYNTAX 9). Whether PCI benefit extends to higher SYNTAX or left main disease in TAVI candidates is not established by this trial.

Connections

• Related to concepts/TAVI — the valve intervention in which PCI is adjunctive
• Related to concepts/Aortic-Stenosis — the primary indication driving TAVI
• Related to concepts/Fractional-Flow-Reserve — physiological lesion assessment tool used in NOTION-3
• Related to entities/Chronic-Coronary-Disease — the stable CAD phenotype in TAVI candidates
• Related to concepts/NSTEMI-Elderly-Invasive-Strategy — shared population (elderly, often frail patients with coronary disease)

Sources

• sources/PCI-TAVI-NOTION3-NEJM-2024