Bifurcations - What Have we Learned from Randomised Trials?

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In percutaneous coronary intervention, bifurcations are a challenging lesion subset and treatment results are dependent on lesion assessment and operator experience. In recent years, a number of well designed and performed randomised clinical trials have dealt with different aspects of the bifurcation lesion procedure. Results from these trials may be helpful in planning a successful bifurcation treatment. Balloon angioplasty and use of bare metal stents are associated with high rates of restenosis in bifurcation lesions. Drug-eluting stents reduce restenosis in these procedures to levels close to non-bifurcation lesion treatment and should be used, if possible. It may be recommended to use the simple strategy of optional stenting of the side branch. The fundamental safety and efficacy of this strategy has been extensively documented in a number of randomised clinical trials. Typically, this strategy may be implemented as the so called ‘step-by-step approach’. However, using drug-eluting stents, also two-stent bifurcation treatment using the culotte or different T-stenting techniques or crush techniques, are associated with excellent short- and long-term results. When two-stent techniques are used, the procedure should always be finalised with a kissing balloon dilatation. However, in the one-stent bifurcation treatment, kissing balloon dilation does not seem to be mandatory, but may be recommended in genuine bifurcations. It must be borne in mind that the general applicability of randomised clinical trials may be limited by inclusion of selected patients. Using drug-eluting stents and a variety of stenting techniques, the randomised bifurcation trails have documented excellent clinical results in the treatment of this complex lesion subset. Therefore, the results from these trials leave room for operator judgement in the selection of the specific bifurcation treatment based on patient and lesion characteristics and personal experience.

Disclosure:Leif Thuesen has received unrestricted study grants from Cordis and Abbott. Niels Ramsing Holm has no conflicts of interest to declare.



Correspondence Details:Leif Thuesen, Department of Cardiology, Aarhus University Hospital, 8200 Aarhus N, Denmark. E:

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Bifurcation lesions are frequent and account for about 15 % of all percutaneous coronary intervention cases.1 Bifurcations are a challenging lesion subset involving a main vessel (MV) and its side branch (SB). A bifurcation lesion may be looked upon as the proximal MV, the distal main vessel, the SB and the area of the bifurcation. Short- and long-term results depend on optimal handling of all parts of the bifurcation, but the choice of treatment should also depend on the condition of the patient and the experience of the operator.

The randomised controlled trial is the cornerstone of evidence-based medicine. Although not all aspects of the bifurcation lesion treatment have been assessed in randomised studies, there are considerable randomised data on bifurcation lesion treatment, such as the use of drug-eluting stents (DES) versus bare metal stents (BMS), the use of one versus two stents, different two-stent strategies and the necessity of kissing balloon (KB) dilatation. The results of the randomised bifurcation trials may help individual operators planning the optimal interventional strategy for individual patients and a wide range of lesion pathology.

Balloon Angioplasty and Bare Metal Stents

Results with balloon angioplasty in bifurcation lesions were poor with high risk of acute closure of MV or SB and with a high restenosis rate.1,2 The use of BMS eliminated the risk of acute vessel closure but was associated with high restenosis rates, especially if two-stent techniques were used.3,4

Drug-eluting Stents

The use of DES in both MV and SB has reduced the problems of acute side branch closure and restenosis in coronary bifurcations. At present, there are no randomised studies specifically comparing DES and BMS in bifurcation lesions. However, data from the bifurcation subgroup of the SCANDSTENT study5 (DES versus BMS in complex coronary lesions) demonstrated that the use of the sirolimus-eluting (SES) Cypher stent (Cordis) reduced restenosis and new revascularisations in bifurcation lesions dramatically. In the bifurcation sub-group of this study including 124 patients, the seven-month target vessel lesion revascularisation rates were 6.0 % in SES versus 21.1 % in BMS-treated patients. The angiographic restenosis rates were substantially reduced from 28.3–4.9 % in the main branch and from 43.4–14.8 % in the SB.

Significant reduction of target lesion revascularisation (TLR) was also demonstrated in a study comparing BMS versus the paclitaxel-eluting Taxus stent (Boston Scientific) in patients with unprotected left main coronary lesions.6 Therefore, despite the lack of lesion-specific randomised investigations, based on extensive clinical short- and long-term data on the use of DES versus BMS in on- and off-label use lesions,7,8 the use of DES may be strongly recommended in bifurcation lesion treatment.

One Versus Two Stents

While there are no randomised trials from the BMS era assessing different stent strategies in bifurcation lesions, there are seven randomised studies comparing a strategy of stenting both MV and SB versus stenting the MV and optional SB stenting using DES.9–15 SES was the study stent in all studies with the exception of BBC I10 and the Chinese double kissing (DK) crush versus provisional side branch stenting study (DKCRUSH-II),9 using the paclitaxel-eluting Taxus stent and the sirolimus-eluting bioabsorbable polymer Excel stent (JW Medical Systems, Weihai, China), respectively. The overall message from these studies has been that the results of DES treatment of coronary bifurcations are excellent in both bifurcation stenting strategies. Thus, the MACE rates have been low and similar in the two treatment groups, but procedure time, fluoro time and the use of contrast have been increased in the more complex strategy of stenting both MV and SB. Also, procedure-related myocardial infarction has been more frequent in two-stent technique groups. However, the prognostic significance of procedural myocardial infarctions is a matter of debate.

The DKCRUSH-II9 results differ from the general finding of equally good results in one- versus two-stent techniques. In this study, a balloon crush of the SB stent was followed by a KB dilatation before stenting of the MV with re-crushing of the SB stent and then a final KB dilatation. In this study, the TLR and restenosis rates were significantly increased in the one-stent group, and actually at a rather high level as compared to the one-stent group of the other randomised one- versus two-stent studies.

The increased TLR- and restenosis rates in the one-stent group of the DKCRUSH-II study did not translate into significantly increased MACE rates. Thus the overall clinical results are remarkably similar in these randomised bifurcation studies, although there were significant differences in the two-stent techniques used. The BBC I10 used crush and culotte techniques, Nordic I13 crush, culotte and T-stenting, the BBK12 T-stenting and Cactus11 conventional crush techniques. There were also differences in the recommendation for SB treatment. With the exception of the conservative approach of NORDIC I,13 where SB stenting was allowed only in case of SB occlusion, the other studies recommended SB stenting in case of SB occlusion or significant SB stenosis after MV stenting. These differences are likely to explain the different crossing over rates in the one- versus two-stent bifurcation studies.

The risk of stent thrombosis was a concern, when DES were used off-label in these complex coronary anatomies, but none of the studies have reported an excess of stent thromboses in these patients irrespective of the use of one- or two-stent techniques, and the risk of stent thrombosis in DES-treated bifurcations seems to be at the same levels as in the large all-comers registries comparing BMS and DES treatment.8

Stenting of Both Main Vessel and Side Branch

The provisional SB stenting strategy may be recommended in most bifurcation cases. However, in situations where the SB has a large diameter and a long lesion, complete lesion coverage could be considered using elective stenting of both MV and SB. Here, there are a number of different options, i.e. the crush technique, the T-technique with or without internal crushing of the SB stent as in the BBK study and the culotte stenting. Furthermore, dedicated bifurcation stents have been introduced to facilitate lesion coverage and minimise technical problems related to the use of conventional stents in coronary bifurcations. So far, there are only two larger randomised clinical trials comparing two-stent techniques: the DKCRUSH-I study16 comparing classical crush and the DK-crush techniques and the Nordic Stent Technique study17 comparing crush versus culotte stenting. In DKCRUSH-I the additional kissing step reduced eight-month MACE rates to 11.4 % compared to 24.4 % in the classical crush group.

In the Nordic Stent Technique study including 424 patients with bifurcation lesions we saw similar six-month clinical outcome and slightly improved eight-month angiographic SB results in the culotte group. Thus, the MACE rates were 4.3 versus 3.7 % and the in-segment restenosis of MV and/or SB were found in 12.1 versus 6.6 % in the crush and culotte groups, respectively.

Kissing Balloon Dilatation

Although no randomised data, registries or sub-group analyses concurrently indicate that the above mentioned bifurcation two-stent techniques should be finalised by a KB dilatation, it is considered mandatory to perform KB dilatation after deploying both a MV and an SB stent.18 However, most patients will be safely and effectively treated with a provisional SB-stenting strategy. Using this strategy, it is not known if the MV stent should be opened at the SB ostium by SB rewiring through the MV stent and subsequent KB dilatation. On the one hand, it might be expected that there is less risk of ostial restenosis due to neointimal bridges on floating struts and that SB blood flow would improve after opening the MV stent at the SB ostium. On the other hand, additional procedural steps, the risk of SB dissection and distortion of the MV stent might be a concern.

The role of KB dilatation was addressed in the THUEBIS pilot trial,19 including 110 patients and in the Nordic-Baltic Bifurcation III study20 including 477 patients. In the latter study, there were stringent criteria for SB stenting, and the crossover rate was low. Thus, any SB dilatation was performed only in 2.5 % of the patients in the no-KB-group, and the crossover rate from no-KB to KB strategy was 0.8 %. The six-month MACE rates were 2.9 versus 3.3 % in the KB and no-KB groups, respectively. At eight-month angiographic follow-up, there were insignificant differences in the binary restenosis rates in favour of KB dilatation. However, in the sub-group of patients with a genuine bifurcation lesion, there were significantly less SB restenosis in patients treated with KB dilatation (7.6 versus 20.0 %). While awaiting long-term data from this study, the mid-term results suggest that in non-true bifurcation lesions, KB dilation should only be performed in cases with compromised SB flow or server ostial pinching after deploying the MV stent. In true bifurcation lesions final KB dilation may be recommended.

Limitations and Clinical Implications

There are a number of limitations in the randomised clinical trials on bifurcation lesion treatment. In these well designed studies, it is difficult to avoid selection of patients especially suited for the study treatment. Furthermore, most of the studies included 0–45 % of non-genuine bifurcations and some of the SBs may have been too small to be clinically significant. These limitations should be considered and warn against general applicability of the results. Still, the results of the use of DES in bifurcation lesions are very promising both in procedures using one or two stents and in the most commonly used two-stent techniques. Furthermore, KB dilatation may be omitted in patients treated with stenting of the main vessel only, especially if dealing with a non-genuine bifurcation. Therefore, the randomised bifurcation trials leave room for operator judgement in the selection of a specific bifurcation treatment based on patient and lesion characteristics and personal experience.

However, based on the simplicity and safety of the optional SB stenting strategy, this approach may be generally recommended in the treatment of coronary bifurcation lesions and is often referred to as the ‘step-by-step approach’.

The Step-by-step Approach

This is the standard bifurcation strategy at many centres and may be carried out in different ways. The strategy described below was used in the Nordic Bifurcation Study. We have found this approach safe and efficient and use the approach in the vast majority of our bifurcation lesion treatments. The technique is shown in Figure 1 and may be described step-by-step as follows.

  • Wiring of MV and SB.
  • Balloon pre-dilatation of main vessel and at operator’s discretion of the SB.
  • Stenting of MV with both wires in place.
  • Optional post-dilatation of the proximal part of the MV.
  • If the flow in the SB is normal (TIMI 3 flow) after stenting the main vessel, the procedure is terminated.
  • If the SB TIMI flow rate is <3, or there is a severe stenosis at the SB ostium of a large SB, the SB is dilated through the MV stent struts.
  • The SB is stented, if the SB TIMI flow rate is 0 after dilatation. Thus, SB stenting is not indicated merely because of residual stenosis or non-flow limiting dissection.
  • In case of SB stenting, Culotte or T-stent technique with or without crush techniques may be applied.
  • In case of SB stenting, the procedure should be finalised by a KB dilatation.


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