Comparison of HYBRID Versus Two-Stent Strategies in Unprotected True Left MAIN Bifurcation
- Conditions
- Unprotected Left Main Coronary Artery Disease
- Registration Number
- NCT07159737
- Lead Sponsor
- Hospital Sultanah Bahiyah
- Brief Summary
The number of deaths from heart disease is rising globally, particularly in developing countries. This condition involves the narrowing of arteries that supply blood to the heart. The most critical narrowing occurs in the left main coronary artery (LMCA), which supplies blood to over two-thirds of the heart muscle. Treating this narrowing is essential to prevent heart attacks or death. The LMCA divides into two branches, known as a bifurcation, both of which require treatment if narrowed.
Currently, narrowing in both branches-the left anterior descending artery (LAD) and the left circumflex artery (LCx)-is treated with a two-stent strategy, where metallic stents are placed in each branch to keep the arteries open. However, this approach is prone to re-narrowing, particularly at the origin of the LCx. A new procedure, called the hybrid strategy, offers an alternative. It involves placing one stent in the LMCA and LAD while inflating a special balloon in the LCX. This balloon, known as a drug-coated balloon, releases a chemical that reduces narrowing over time without needing a stent. At present, there is uncertainty which strategy is better. This study will assess whether the hybrid strategy is more effective than the two-stent strategy in preventing death, heart attacks, and re-narrowing of the arteries.
Participants will have an equal chance of receiving either the two-stent or hybrid strategy and will only join the study if their doctor is unsure which method is best. To minimise the burden on participants, all study procedures and follow-ups will be integrated into standard routine care.
The results of this study have the potential to offer a new, safer treatment that could save the lives of millions of people with this condition.
- Detailed Description
Percutaneous coronary intervention (PCI) of unprotected distal left main bifurcation (UTLMB) lesions remains technically demanding and is associated with higher risks than interventions in non-left main coronary lesions.
Several revascularisation strategies are in use:
* Provisional strategy - Implant a single drug-eluting stent (DES) from the left main coronary artery (LMCA) to the left anterior descending artery (LAD), leaving the left circumflex artery (LCx) unstented.
* Stepwise provisional strategy - Begin with the LMCA to LAD DES as in the provisional strategy, then implant a stent in the LCx only if required (e.g., for flow limitation or suboptimal angiographic result) using the operator's preferred method.
* Two-stent strategy - From the outset, plan to implant DES in both LAD and LCx using a recognised bifurcation technique.
* Hybrid strategy - Implant a DES from LMCA to LAD and treat the LCx with a drug-coated balloon (DCB) after adequate preparation and in the absence of a flow-limiting dissection.
While provisional approaches are less complex, they may be inadequate in true bifurcation lesions where both branches have significant disease.
Conversely, two-stent strategies offer full anatomical coverage but are technically challenging, associated with longer procedures, greater contrast use, higher radiation exposure, and potentially more periprocedural complications. Optimal outcomes heavily depend on the operator's skill, which contributes partly to the ongoing debate on this topic. Regardless of the operator's skill or chosen two-stent approach, the persistent risk of restenosis at the LCx ostium remains a significant vulnerability in the two-stent strategy.
The interventional cardiology community in the Asia-Pacific region remains divided on the optimal management of UTLMB due to differing philosophical and ideological approaches: the stepwise provisional strategy versus the upfront two-stent strategy. This uncertainty stems from conflicting results of two major RCTs focused on UTLMB.
The European Bifurcation Club MAIN (EBC MAIN) trial examined the stepwise provisional strategy, where a stent is placed from the LMCA to the LAD, and a second stent is added to the LCX only if necessary. Although underpowered, this trial found no significant difference in clinical outcomes at one year compared to the upfront two-stent strategy. However, recent three-year outcomes favour the stepwise provisional approach with lower repeat revascularisation rates.
Conversely, the DKCRUSH-V trial, conducted predominantly in Chinese centres with some sites outside China, compared an upfront two-stent strategy (double kissing crush \[DK crush\] technique) to a provisional strategy, showing better clinical outcomes at one year with the two-stent approach, with similar benefits at three years. The DK crush technique involves stenting the LCx first, followed by the LMCA to LAD.
The Hybrid Strategy, combining a DES and a DCB, has the potential to achieve full revascularisation while minimising metal implantation, preserving vessel compliance, and reducing late restenosis risk. Moreover, the hybrid strategy is technically less demanding and avoids the additional steps involved in the two-stent approach. Consequently, this approach is less dependent on the experience of the operator and can be more readily integrated into clinical practice. However, this approach has not yet been evaluated in a large-scale randomised controlled trial (RCT) for UTLMB lesions.
Asia-Pacific Perspective:
The burden of left main coronary artery disease is substantial in the Asia-Pacific region, where cardiovascular disease (CVD) remains the leading cause of mortality. Compared with Western populations, patients in this region often present with more diffuse and complex coronary artery disease (CAD). In many areas, there is limited availability of cardiothoracic surgeons, making PCI a more practical and timely option than coronary artery bypass graft surgery (CABG). There is also a strong patient preference for PCI over CABG, influenced by cultural factors, perceptions of surgical risk, and the shorter recovery time associated with PCI.
Interventional cardiology practice in the Asia-Pacific is characterised by high procedural volumes and substantial expertise in complex PCI techniques, including bifurcation stenting. DCBs are widely available and routinely used in parts of the region. These differences in patient characteristics, treatment preferences, procedural expertise, and technology access underpin the need for region-specific evidence.
The HYBRID MAIN trial has therefore been designed specifically for the Asia-Pacific setting, ensuring its findings will be directly relevant to the populations and healthcare systems most likely to benefit.
Primary Objective:
To determine whether a hybrid PCI strategy (DES from LMCA to LAD + DCB to LCx) is superior to an upfront two-stent strategy in reducing target lesion failure at 2 years in patients with UTLMB lesions suitable for both strategies
Trial Design:
The HYBRID MAIN trial is a streamlined, multicentre, open-label, randomised controlled trial (RCT) conducted exclusively in the Asia-Pacific region, testing the superiority of a hybrid strategy compared with an upfront two-stent strategy for UTLMB lesions.
Common principles:
* De novo UTLMB
* IVUS is mandatory for vessel sizing and lesion length before randomisation.
* LCx preparation must achieve residual stenosis \< 30% without flow-limiting dissection.
* Operators preference to decide between upfront two-stent strategy or stepwise provisional approach
Eligible patients will be randomly allocated in a 1:1 ratio to receive either:
* Hybrid strategy: DES from the LMCA to the LAD with DCB to the LCx.
* Two-stent strategy: Implantation of DES in LMCA to the LAD and LCx using the operator's preferred bifurcation technique.
Pilot Phase:
The trial will commence with an internal pilot phase across selected high-volume PCI centres in Malaysia. The pilot will enrol the first 50 patients; if feasibility criteria are met, the trial will expand to multiple centres across the Asia-Pacific region.
Inclusion of High-volume Operators:
Only operators performing \>300 PCI cases/year (including ≥20 left main interventions/year) will randomise patients. High-volume operators are more likely to apply the floating eligibility criteria effectively, achieve optimal procedural results, and minimise crossovers.
Recruitment:
Pre-screening performed by the operator based on diagnostic angiograms to determine whether the patient is potentially suitable for both strategies when substantial uncertainty exists. This aligns the trial with real-world decision-making and avoids unnecessary clinic visits for unsuitable cases.
Screening against the floating eligibility criteria, confirming:
* Unprotected distal LM true bifurcation (Medina 1,1,1; 1,0,1; and 0,1,1) with substantial uncertainty between both strategies
* Ability to give informed consent
* Pre-randomisation information
Written consent obtained before procedure wherever possible.
For patients identified during a coronary angiogram, urgent PCI may be required due to clinical indications or patient requests, with the operator deciding on the table. In these cases, pre-screening, screening, and consent occur simultaneously. For such cases, verbal consent may be obtained with written consent completed after the procedure.
After wiring both LAD and LCx;
* LAD and LCx vessel reference vessel diameter (RVD) and lesion length measured by IVUS before lesion preparation undertaken.
* Optimal lesion preparation in LCx with residual stenosis less than 30%, TIMI 3 flow without a flow-limiting dissection.
* May be part of stepwise provisional or upfront two-stent before randomisation.
Follow-up:
All patients will be followed for a mean of 2 years from the date of randomisation. Follow-up will be conducted by telephone or clinic visits, with medical record review as required. Post-trial follow-up will be done annually till 5 years post randomisation to look for long term clinical outcomes (TLF).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1708
Not provided
- Protected left main (patent graft to LAD and LCX)
- Need for anticoagulation
- LCx reference vessel diameter less than 2.5 mm (< 2.5 mm)
- Cardiogenic shock
- Severe left ventricular (LV) dysfunction making either strategy unsafe
- Contraindication to antiplatelet therapy or study devices
- Life expectancy less than 2 years
- Participation in another trial that may affect results
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Target Lesion Failure (TLF) 2 years Target lesion failure (TLF) at 2 years defined as a composite of: time to first event of cardiovascular death, time to first event of target vessel myocardial infarction (TVMI), time to first event of clinically driven target lesion revascularisation (CD-TLR).
- Secondary Outcome Measures
Name Time Method Composite of cardiovascular death and TVMI 2 years Composite of objective endpoints included in TLF
* time to first event of cardiovascular death
* time to first event of TVMISafety endpoints 2 years Time to first event of stent/lesion thrombosis
Individual components of primary endpoint 2 years Time to first event of individual components of TLF
* time to first event of cardiovascular death
* time to first event of TVMI
* time to first event of CD-TLR