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4.4.5.3 Patients with multivessel coronary artery disease

The SYNTAX and SYNTAXES randomized trials, comparing PCI and CABG for multivessel CAD with or without unprotected LMCAD, reported differences in terms of survival and freedom from cardiovascular events dependent on SYNTAX score.795,798,823 The recently published 10-year follow-up results of the SYNTAX trial (SYNTAXES trial) reported similar all-cause death rates with both revascularization modalities,795 while there was significantly higher mortality in patients with SYNTAX scores ≥33 who were randomized for PCI (HR 1.41; 95% CI, 1.05–1.89).795 A significant 5-year mortality gap between PCI and CABG has been reported among patients with complex multivessel CAD in the presence of DM (15.7% after PCI vs. 10.7% after CABG; HR 1.44; 95% CI, 1.20–1.77; P = .0001).728 In the FREEDOM trial (Strategies for Multivessel Revascularization in Patients with Diabetes), 1900 patients with diabetes and multivessel disease without LMCAD were randomized to CABG vs. PCI (using first-generation DES). Long-term results at a median follow-up duration of 3.8 years [interquartile range (IQR) 2.5–4.9 years] showed higher all-cause mortality in the PCI group vs. CABG group (24.3% vs. 18.3%; P = .01).801 Out of all the centres that participated in the study, only 25 agreed to participate in the FREEDOM extended followup, and therefore, only 49.6% of patients in the study were followed up for up to 8 years thus limiting statistical power. The all-cause mortality rate among the FREEDOM follow-up patients was not significantly different between those who underwent PCI and CABG procedures (23.7% vs. 18.7%; HR 1.32; 95% CI, 0.97–1.79; P = .076). In multivariable analysis, a significant interaction emerged between patient age and longterm survival benefit of CABG surgery. Patients younger than the median age at study entry (63.3 years) preferentially derived benefit from CABG; mortality among patients ≤63.3 years old was 20.7% (PCI) vs. 10.2% (CABG); mortality among patients >63.3 years old was 26.3% vs. 27.6% (P = .01 for interaction).824

4.4.5.4 Impact of coronary pressure guidance on multivessel coronary

artery disease patients undergoing percutaneous coronary intervention Consistently higher rates of repeat revascularizations following PCI compared with CABG have been shown in clinical trials involving multivessel CAD patients, with significant impacts on outcomes.825 With the use of modern DESs, the rate of repeat revascularization after PCI has declined.725,795,802,820 FFR guidance during PCI leads to lower revascularization rates compared with angiography-guided PCI, with fewer stents placed in the FFR group.826 In the FAME 3 trial, 1500 patients with three-vessel CAD not involving the LMCA were randomly assigned to PCI with second-generation DESs (durable polymer zotarolimus-eluting stents) guided by FFR, or to CABG.326 At 1-year follow-up, the incidence of the composite primary endpoint, MACCE [major adverse cardiac (death from any cause, MI, stroke, or repeat revascularization) or cerebrovascular events], was 10.6% among patients assigned to FFR-guided PCI and 6.9% among patients assigned to CABG surgery (HR 1.5; 95% CI, 1.1–2.2), findings that were not consistent with non-inferiority (P = .35 for noninferiority).326 At 3-year follow-up, there still was a significantly higher rate of MACCE for PCI than for CABG (18.6% vs. 12.5%; HR 1.5; 95% CI, 1.2–2.0; P = .002), consistent with the 1-year follow-up results. However, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% vs. 9.2%; HR 1.3; 95% CI, 0.98–1.83; P = .07). The rates of death (4.1% vs. 3.9%; HR 1.0; 95% CI, 0.6–1.7; P = .88) and stroke (1.6% vs. 2.0%; HR 0.8; 95% CI, 0.4–1.7; P = .56) were not different, while MI again occurred more frequently after PCI (7.0% vs. 4.2%; HR 1.7; 95% CI, 1.1–2.7; P = .02).827 Repeat revascularization was also more frequent after PCI (11.1% vs. 5.9%; HR 1.9; 95% CI, 1.3–2.7; P = .001). Of note, after both PCI and CABG, event rates were lower (about half for mortality) than in the SYNTAX cohort of patients with three-vessel CAD. There was a narrower difference for MI rates between the two modalities, probably owing to procedural advances with PCI and CABG and improvements in GDMT. In patients with less complex CAD (SYNTAX score ≤22), outcomes were as favourable as after CABG.

4.4.5.5 Virtual percutaneous coronary intervention: combination of

coronary pressure mapping with coronary anatomy for percutaneous coronary intervention planning There is increasing evidence on the impact of post-PCI FFR/iFR/QFR on outcomes after PCI.828–833 A quarter of these patients have residual ischaemia (FFR < 0.80 or iFR ≤ 0.89) after angiographically successful PCI, with circa 80% of cases attributable to focal lesions not identified by angiography alone.830 One randomized trial reported that post-PCI iFR/FFR can be improved by additional intracoronary intervention, including post-dilatation or additional stent implantation, but remains ≤0.80 in 18% of cases.829 Preliminary results demonstrate that the combination of invasive coronary pressure mapping by iFR pullback or QFR mapping superimposed on the anatomical information of ICA accurately predict the post-PCI coronary pressure for any combination of stent location and stent length, as part of a ‘virtual PCI’ approach,348,834 and allows modification of the procedural planning in about 30% of cases.835 The AQVA (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR) trial (n = 300) demonstrated that a strategy of QFR/ICA-based virtual PCI was associated with a higher rate of post-PCI QFR ≥0.90 compared with angiography-based PCI (93.4% vs. 84.9%, P = .009).836 The DEFINE GPS trial (NCT04451044) is currently investigating the clinical benefit of pre-procedural coronary pressure mapping with iFR pullback and ‘virtual PCI’ to clarify this issue further and improve post-PCI clinical outcomes. Virtual PCI can be conducted by combining anatomical information from CCTA with that of FFR-CT. FFR-CT/CCTA-based virtual PCI has two theoretical advantages over ICA-based virtual PCI: (i) it does not require invasive investigation, and (ii) it provides information on vessel wall/ plaque composition.837 FFR-CT/CCTA-based virtual PCI has been shown to accurately predict post-PCI FFR838 and to modify PCI procedural planning in 31% of lesions and 45% of patients.839 The Precise Procedural and PCI Plan (P4) trial (NCT05253677) is currently investigating the clinical benefit of iFR-based virtual PCI to clarify this issue further and improve post-PCI clinical outcomes.

4.4.5.6 Impact of intracoronary imaging guidance on multivessel

coronary artery disease patients undergoing percutaneous coronary intervention Three large randomized trials have recently investigated the clinical benefit of intracoronary imaging during ‘complex’ PCI. One trial, RENOVATE-COMPLEX PCI,840 mainly investigated the benefit of IVUS (74% IVUS, 26% OCT), while the two others, OCTOBER810 and ILUMIEN IV,841 investigated the benefit of OCT. Importantly, while OCTOBER (true bifurcation lesions) and RENOVATE- COMPLEX PCI (including true bifurcation lesions, long lesions, Downloaded from academic.oup.com/eurheartj/article/45/36/3415/7743115 by guest on 07 October 2026