Bifurcation left main stenting with or without intracoronary imaging: Outcomes from the EBC MAIN trial

Selected in Catheterisation & Cardiovascular Interventions by A. Cader , S. R. Khan

This sub-analysis of EBC MAIN aimed to determine if intracoronary imaging use during LM bifurcation PCI was associated with fewer MACE, for patients treated with a planned dual‐stenting strategy versus provisional strategy.

Reviewers

Aaysha Cader

@aayshacader

Cardiology SpR

Kettering General Hospital NHS Foundation Trust - Kettering, United Kingdom

Saidur Rahman Khan

@drsaidurrahman2

Interventional cardiologist / Cardiologist

Ibrahim cardiac hospital and research institute - Dhaka, Bangladesh

Our Comment

Why this study? – the rationale/objective

Left main (LM) bifurcation PCI can be a technically demanding procedure. Intravascular imaging may be useful in improving clinical and procedural outcomes. In the EBC MAIN trial (European Bifurcation Club LM Coronary Stent study), there were numerically fewer major adverse cardiac events (MACE) between a stepwise layered provisional approach versus planned dual stenting in true bifurcation lesions, albeit not statistically significant¹.

This sub-analysis of EBC MAIN aimed to determine if intracoronary imaging use during LM bifurcation PCI was associated with fewer MACE, for patients treated with a planned dual‐stenting strategy versus provisional strategy².

Additional aims included determining the effect of intracoronary imaging on clinical outcomes, in relation to angiographic and procedural aspects of bifurcation PCI: i.e. extent of lesion calcification, lesion length in the side branch (SB), and stent length in the main vessel (MV).

How was it executed? - the methodology

The EBC MAIN trial randomised 467 patients with  LM bifurcation lesions to provisional single stent group, or to upfront dual stenting. Intracoronary imaging was not mandated by protocol in the EBC-MAIN trial. The use of either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was undertaken at the operator's discretion.

The primary endpoint was a composite of all-cause death, myocardial infarction (MI) or target vessel revascularization (TVR) at  1 year.

Statistical analysis:  The trial endpoints were assessed using logistic regression or cox regression. Multivariate analyses were done to provide adjusted odds ratios (OR) and hazard ratios (HR); population characteristics that differed significantly between intracoronary imaging and angiography-guidance only were included as covariates in the model, i.e. ischaemic symptoms, syntax score and lesion calcification. Regression models were used to assess treatment effects through interactions.

Sub-groups were pre-specified according to procedural characteristics hypothesized to affect any association between intracoronary imaging use and the primary outcome:

1. bifurcation PCI strategy (dual‐stent vs. provisional)
2. SB lesion length (<10mm vs.≥10 mm)
3. MV stent length (<28mm vs. ≥28 mm)
4. angiographically defined extent of calcification (moderate-severe vs. none‐mild).

All tests were assessed at the 5% significance level. No adjustments were made for multiple testing.

What is the main result?

Among 467 trial patients, 12 were excluded in this sub-analysis due to missing data (n=9) and non-performance of LM PCI (n=3). Of these 455 patients, 226 had been randomized to the provisional stepwise approach, and 229 to the systematic dual-stent approach².

Procedural characteristics

Angiography guidance alone was used in 61% patients. Intracoronary imaging was used in 179 (39%) of participants. The majority underwent IVUS = (n= 151, 33%), with only 6% (n=28) of patients had OCT.

Intracoronary imaging use was similar with the stepwise provisional strategy (40%) as with the systematic dual-stent approach (38%). In 33% of cases, the operators had planned to perform IVUS at the start of the case, which was 84.6% of those who were imaged in provisional stepwise strategy, and 79.5% of systematic dual strategy.

Imaged vessels: Among those who had IVUS, 87 (48.6%) had both MV and SB imaged; this was only 38.5% of provisional stenting, but 59.1% for systematic dual stenting. Sixty four (42%) had only the MB imaged, which was 49.5% of provisional stentings and 21.6% of dual stentings.

Overall, as a result of IVUS findings, operators re-intervened in 42 (27.8%) of procedures, either with a balloon or stent.  Re-intervention was more frequent in the stepwise provisional group(n=28, 30.8%), while 14 (15.9%)were in the systematic dual-stent group.

Clinical outcomes

Overall, the primary composite outcome of death, MI or TVR at 1 year occurred in 73 participants (16%), with no difference for patients who had intracoronary imaging versus angiography-guidance (17% vs. 16%; OR: 0.92 [95% CI: 0.51−1.63] p = 0.767; HR: 0.94 [95% CI: 0.55−1.59] p = 0.812), after adjustment for covariates, i.e. syntax score, lesion calcification and ischemic symptoms

Overall, as a result of IVUS findings, operators reintervened in 42 procedures. There were also no differences in the primary outcome for those who had reintervention based on IVUS findings compared to the rest of the participants (14% vs.16%; adjusted OR: 0.88 [95% CI: 0.32−2.43] p = 0.803; adjusted HR: 0.87 [95% CI: 0.34−2.12] p = 0.774).

PCI strategy, intravascular imaging & outcomes: There was a significant interaction between intracoronary imaging use and LM bifurcation PCI strategy, with respect to the primary outcome (p = 0.009). Among those who underwent stenting with angiographic guidance alone, the prevalence of the primary outcome was higher in the dual stenting arm, as compared to provisional stenting arm (21% vs. 10%; adjusted OR: 2.11 [95% CI: 1.04−4.30] p = 0.039). With intracoronary imaging, no differences were seen for primary outcome events, although they were numerically fewer with dual versus provisional stenting (13% vs. 21%; adjusted OR: 0.56 [95% CI: 0.22−1.46] p = 0.220).

A significant interaction was noted between intracoronary imaging use and LM bifurcation PCI strategy with respect to MI and periprocedural MI (p = 0.015 and p = 0.035 respectively). There were no interactions for intracoronary imaging use and the primary outcome, with respect to:

1. extent of calcification,
2. SB lesion length,
3. MB stent length.

Critical reading and the relevance for clinical practice

The findings of this sub-study must be interpreted on the background that intravascular imaging use in the EBC MAIN population overall, was ~40%, and that patients were not randomised to imaging vs angiography-guidance.

Apart from this selection bias, the use of imaging was left to operator discretion, and thus the timing of its use during the procedure is not known, raising the possibility that imaging may have indeed been used to rectify a complication or poor outcome, and not necessarily to guide optimum stenting strategy. SB optimization is an important component of better outcomes in bifurcation PCI. The impact of imaging in both MV and SB imaging was also not assessed in this study, and remains an area of further research

The use of OCT in this study was low, with no data on re-intervention based on OCT findings. Furthermore, the study was also not powered to detect significant interactions between intracoronary imaging use, the primary outcome, and additional factors, and the results must therefore be interpreted as exploratory.

On the background of these caveats, this sub-analysis suggests that intravascular imaging is important to optimise outcomes, particularly in dual-stent strategies in LM bifurcations. While dedicated randomised controlled trials for LM bifurcation PCI can be challenging to recruit, two separate upcoming trials are compare MACE for both LM & non-LM bifurcation PCI.

The OCTOBER (European randomized Optical Coherence Tomography Optimized Bifurcation Event Reduction) trial (NCT03171311), the results of which will be presented later this month, compares 2-year MACE for OCT vs angiography-guided bifurcation PCI, in LM & non-LM disease in European centres³. The DKCRUSH VIII (IVUS Guided DK Crush Stenting Technique for Patients with Complex Bifurcation Lesions, NCT03770650) is comparing 1-year MACE  for an IVUS-guided versus angiography-guided dual-stenting DK Crush strategy for complex bifurcation lesions, including LM bifurcations⁴.

References

1. Hildick-Smith D, Egred M, Banning A, et al. The European bifurcation club Left Main Coronary Stent study: a randomized comparison of stepwise provisional vs. systematic dual stenting strategies (EBC MAIN). Eur Heart J. 2021 Oct 1;42(37):3829-3839. doi: 10.1093/eurheartj/ehab283.
2. Maznyczka A, Arunothayaraj S, Egred M, et al; EBC MAIN (European Bifurcation Club Left Main Coronary Stent study) investigators. Bifurcation left main stenting with or without intracoronary imaging: Outcomes from the EBC MAIN trial. Catheter Cardiovasc Interv. 2023 Jul 20. doi: 10.1002/ccd.30785. Epub ahead of print.
3. Holm NR, Andreasen LN, Walsh S, et al. Rational and design of the European randomized Optical Coherence Tomography Optimized Bifurcation Event Reduction Trial (OCTOBER). Am Heart J. 2018 Nov;205:97-109. doi: 10.1016/j.ahj.2018.08.003.
4. Ge Z, Kan J, Gao XF, et al. Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial. Am Heart J. 2021 Apr;234:101-110. doi: 10.1016/j.ahj.2021.01.011.