Cardiology · Medical Literature
Side Branch Additional Treatment for Coronary Bifurcation Lesion Revascularization: Insights From the KISS Randomized Trial.
Abstract
Although provisional stenting is the recommended strategy for most coronary bifurcation lesions, the clinical benefit of additional side branch (SB) intervention remains debated. The aim of this study was to determine whether a conservative strategy without systematic SB intervention (SBI) is noninferior to systematic SB intervention regarding periprocedural events. The multicenter, international KISS (Keep Bifurcation Single Stenting Simple) trial randomized patients with non-left main bifurcation lesions to 2 groups: no SBI or SBI following main branch stenting with the Resolute Onyx drug-eluting stent and a proximal optimization technique without impairment of SB flow. The primary endpoint was periprocedural myocardial infarction (MI) or myocardial injury, according to the Academic Research Consortium 2 definition. Secondary endpoints included procedural complications and 12-month clinical outcomes, including target lesion failure, defined as the composite of cardiac death, target vessel MI, and target lesion revascularization. Among the 616 included patients, 81% were treated for chronic coronary disease, and the bifurcation mainly involved was between the left anterior descending coronary artery and the diagonal. In the no-SBI group, an intervention on the SB was required in 2.0% of patients (n = 6). Periprocedural MI or myocardial injury occurred in 4.1% (n = 11) in the no-SBI group vs 5.7% (n = 16) in the SBI group (P < 0.001 for noninferiority; P = 0.38 for superiority). There was no significant interaction with age, sex, Medina classification, or SB residual stenosis. Procedure time, radiation dose, and contrast use were significantly lower in the no-SBI group. Procedural complications were rare, but SB dissection was more frequently observed in the SBI group (2.9% vs 0.0%; P = 0.004). There was no difference in target lesion failure at 1 year (4.9% [n = 15] vs 6.4% [n = 20] in the no-SBI and SBI groups respectively; P = 0.442). The KISS trial demonstrates that a conservative strategy without systematic SB intervention is associated with very rare procedural complications and is noninferior to a systematic SB intervention regarding periprocedural MI and myocardial injury.
Clinical relevance
In patients undergoing provisional stenting with proximal optimization technique (POT) for non-left main coronary bifurcation lesions without side branch (SB) flow impairment, is a conservative strategy of no routine SB intervention noninferior to systematic SB intervention with respect to periprocedural myocardial infarction or myocardial injury? __SNAPSHOT__ {"studyDesign":"Randomized controlled trial (1:1), prospective, open-label, multicenter, noninferiority design","setting":"20 centers across 6 countries (France, Italy, Spain, United Kingdom, Portugal, and Switzerland); enrollment from October 2020 to November 2022","sampleSize":"n=616 (no-SBI group: n=303; SBI group: n=313)","population":"Adults with non-left main coronary artery disease undergoing PCI for de novo bifurcation lesions with significant main vessel (MV) stenosis (≥70% angiographic or FFR ≤0.80) requiring MV stenting, without significant SB flow impairment after MV stenting and POT. Mean age 67.7 ± 10.9 years; approximately 75% male; 81% with chronic coronary disease. LAD/diagonal bifurcation involved in 81.2% of patients.","intervention":"No systematic SB intervention (no-SBI) following MV provisional stenting with the Resolute Onyx drug-eluting stent and proximal optimization technique (POT), with rescue SB intervention permitted only for significant SB flow compromise.","comparator":"Systematic SB intervention (SBI) — including balloon angioplasty and/or kissing balloon inflation — following MV provisional stenting with the Resolute Onyx DES and POT.","primaryOutcome":"Periprocedural myocardial infarction (MI) or myocardial injury per Academic Research Consortium-2 (ARC-2) definition, adjudicated by an independent clinical events committee with core laboratory angiographic review.","followUp":"12 months","fundingSource":"CERIC (Center for European Research Initiatives in Cardiovascular Medicine, Fribourg, Switzerland) and an unrestricted grant from Medtronic (industry). Lead author holds equity in CERC and Colibri; co-investigators report consulting/lecture fees from multiple cardiovascular device companies."}
Key findings
Among 616 randomized patients, crossover to SBI occurred in only 2.0% (n=6) of the no-SBI group, indicating high protocol adherence. The primary endpoint of periprocedural MI or myocardial injury (ARC-2 definition) occurred in 4.1% (n=11) of the no-SBI group versus 5.7% (n=16) in the SBI group (P<0.001 for noninferiority; P=0.38 for superiority). The absolute risk difference favored the no-SBI group by approximately 1.6 percentage points (calculated), though superiority was not demonstrated. Subgroup analyses showed no significant interaction by age, sex, Medina classification, or residual SB stenosis. Procedural efficiency was meaningfully improved in the no-SBI arm: procedure time, radiation dose, and contrast volume were all significantly lower (specific values not reported in available abstract). SB dissection — a clinically important procedural complication — occurred in 2.9% of the SBI group versus 0.0% in the no-SBI group (P=0.004). Stent thrombosis rates at 12 months were low and equivalent (0.7% no-SBI vs. 0.6% SBI; P=0.971). Target lesion failure (TLF) at 12 months — the composite of cardiac death, target vessel MI, and target lesion revascularization — was 4.9% (n=15) in the no-SBI group versus 6.4% (n=20) in the SBI group (P=0.442); the trial was not powered for this secondary endpoint. An exploratory within-SBI-group analysis found that SB balloon angioplasty alone was associated with lower primary endpoint rates compared with kissing balloon inflation (3.4% vs. 8.9%; P<0.001 for noninferiority), but without significant differences in secondary clinical outcomes. Angina symptom improvement at 12 months was greater in the no-SBI group (99.0% vs. 93.7%; P=0.040). Confidence intervals for the primary noninferiority comparison and the prespecified noninferiority margin were not reported in the available abstract.
Practice implications
The KISS trial establishes that, after contemporary provisional stenting with systematic POT and in the absence of significant SB flow impairment, omitting routine SB intervention is noninferior to performing systematic SBI with respect to periprocedural myocardial injury and MI. This result is specific and important: it applies only to non-left main, non-complex bifurcation lesions (predominantly LAD/diagonal) in patients with preserved SB flow post-POT; the findings should not be extrapolated to left main bifurcations, bifurcations with large SBs (>2.5 mm), long or significant SB disease, or cases requiring a two-stent strategy. The conservative strategy also yielded a meaningful reduction in SB dissection, procedure time, radiation, and contrast exposure — all clinically relevant benefits. The 12-month TLF data are directionally consistent with no-SBI being at least equivalent, but the trial was underpowered to confirm noninferiority or equivalence for this hard clinical endpoint. Long-term outcomes beyond 12 months remain unknown. Given that this is an open-label trial and that only an abstract is available for review, caution is warranted in interpreting the full scope of the noninferiority margin, confidence intervals, and subgroup analyses, which could not be independently verified. The angina symptom improvement signal favoring no-SBI requires confirmation. The study corroborates and contextualizes prior trials (e.g., Nordic-Baltic III) by testing the no-SBI strategy within a fully contemporary POT-based provisional stenting framework. __LIMITATIONS__ Open-label design introduces potential ascertainment and adjudication bias, particularly for softer endpoints such as myocardial injury.,Lower-than-anticipated event rates may have resulted in underpowering; the noninferiority margin and precise confidence intervals for the primary endpoint are not reported in the available abstract.,Only the abstract is available for full methodological appraisal; blinding of the core laboratory is not confirmed.,Enrollment was restricted to patients without SB flow impairment after POT, limiting generalizability to higher-risk bifurcation anatomy (left main, large SBs >2.5 mm, complex true bifurcations requiring two-stent techniques).,The population was predominantly male (~75%) and composed largely of chronic coronary disease patients (81%); generalizability to women and acute coronary syndrome presentations is limited.,The 12-month TLF secondary endpoint was not powered for noninferiority or superiority; the directional trend should be considered hypothesis-generating only.,Unrestricted grant from Medtronic (manufacturer of the Resolute Onyx DES used in both arms) and equity interests disclosed by the lead author introduce potential conflicts of interest.,Long-term follow-up data beyond 12 months are absent; durability of the conservative strategy regarding SB restenosis and late clinical events remains unestablished.,Single device (Resolute Onyx DES) used exclusively; findings may not be fully generalizable to other contemporary DES platforms.,Angina improvement as a secondary outcome is highly susceptible to reporting bias in an open-label design. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ The KISS trial demonstrates that in patients with non-left main coronary bifurcation lesions treated with contemporary provisional stenting and systematic POT, omitting routine SB intervention when SB flow is preserved is noninferior to systematic SBI for periprocedural MI and myocardial injury, while also reducing SB dissection, procedure time, radiation, and contrast exposure. These findings support a 'keep it simple' approach — avoiding routine SB intervention after successful MV stenting and POT — in appropriately selected patients with non-complex, non-left main bifurcations and intact post-POT SB flow. Longer-term follow-up and confirmation in broader and higher-risk bifurcation populations are needed before this strategy can be universally applied.