10-Year Final Report of PRECOMBAT Trial: Keeping up with the debate of PCI vs. CABG in LM

August 7th, Highlight Session of TCTAP & AP VALVES 2020 VIRTUAL

Although CABG remains as the gold standard for the treatment of significantly diseased left main coronary artery (LMCA), evidences derived from large scale randomized trials such as SYNTAX, PRECOMBAT, and EXCEL with the exception of NOBLE suggest that percutaneous coronary interventions (PCI) in low or intermediate-risk of anatomical complexity leads to comparable rates of major adverse cardiovascular event rates (MACE) compared to CABG when performed by experienced operators using IVUS-guidance. However, data are still limited on very long-term (beyond 5 years) outcomes of PCI or CABG. Given that some studies reported a trend of late catch-up or crossover in primary outcome favoring CABG over PCI over time, there remains uncertainty about long-term outcomes and it warrants additional longer-term follow-up studies.

The PRECOMBAT (The Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) assessed the non-inferiority of PCI (n = 300) vs. CABG (n = 300) in patients with LMCA disease. Though no significant differences were observed in the rates of MACE among the cohorts, both clinically and ischemia-driven target vessel revascularization (TVR) rates were higher in the PCI cohort reaching statistical significance at 5-years. The subgroup analysis showed that only patients with SYNTAX scores 33 demonstrated increased risk of ischemia-driven TVR while low and intermediate SYNTAX score groups had comparable revascularization rates.

The extended follow-up of PRECOMBAT trial at 10 years presented by Dr. Duk-Woo Park, MD, at the highlight session of TCTAP & AP VALVES 2020 VIRTUAL showed sustained non-inferiority of PCI over CABG with no difference in the risk of death, myocardial infarction (MI), or stroke in the two treatment arms. More specifically, the 10-year incidence of the composite of death, MI, or stroke (18.2% vs 17.5%; HR 1.00 [95% CI, 0.70-1.44]) and all-cause mortality (14.5% vs 13.8%; HR 1.13 [95% CI, 0.75-1.70]) were not significantly different between the PCI and CABG groups. Nevertheless, the rate of ischemia-driven TVR was significantly higher in patients treated with PCI (16.1% vs 8.0%; HR 1.98; 95% CI 1.21-3.21), a consistent observation among most randomized trials assessing PCI vs. CABG for LMCA disease.

The highly anticipated extended follow-up of PRECOMBAT trial provides encouraging insights in the left main PCI landscape especially when looking in aggregate the extended (10 years) follow-up of SYNTAX trial as well showing continued equivalence of PCI vs. CABG for the primary endpoint of all-cause mortality (23.5% in CABG and 27% in PCI groups, p = 0.092); nevertheless, we should take into consideration that the PRECOMBAT trial was not powered for clinical outcomes and the results should be viewed with caution. In addition, the recently reported 5-year results of NOBLE and EXCEL trials (which involved different endpoints) have not clearly shown that a wider adoption of left main PCI in specific clinical subsets is without concerns. The 5-year results of NOBLE (Nordic-Baltic-British Left Main Revascularisation Study) showed that CABG was superior to PCI in a cohort of 1,201 patients with LMCA stenosis (average SYNTAX score of 22.1 7.7) for the primary composite endpoint of all-cause death, non-procedural MI, repeat revascularization or stroke, driven by higher rates of non-procedural MI and repeat revascularization after PCI. Furthermore, the 5-year results of EXCEL showed that the composite endpoint of death, stroke or MI had no significant difference between the cohorts when LMCA disease was of low- or intermediate-anatomic complexity; meanwhile; death (although underpowered) was lower in the CABG group.

Looking at the evidence in aggregate with the rapid innovations in drug-eluting stent designs leading to more biocompatible thin strut platforms with optimal drug elution, the advances in modern pharmacotherapy involving potent P2Y12 inhibitors combined with utilization of intracoronary imaging and physiologic assessment for procedural planning and optimization, PCI tends to have comparable clinical outcomes with CABG in the presence of low or intermediate risk of anatomic complexity and is considered a good alternative to CABG in selected LMCA anatomic territories. Additional evidence from randomized trials with consistent clinical endpoints and meta-analyses focused in establishing the best possible technical approaches to intervene in complex LMCA bifurcations are anticipated to support further utility of PCI in this anatomic territory.

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Editor: Bill (Vasileios) Gogas (Gkogkas), MD (Nanjing First Hospital, China)