Abstract
Background
Improvements in drug-eluting stent design have led to a reduced frequency of repeat revascularisation and new biodegradable polymer coatings may allow a shorter duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).
Aims
The Improved Drug-Eluting stent for All-comers Left Main (IDEAL-LM) study aims to investigate long-term clinical outcomes after implantation of a biodegradable polymer platinum-chromium everolimus-eluting stent (BP-PtCr-EES) followed by 4 months DAPT compared to a durable polymer cobalt-chromium everolimus-eluting stent (DP-CoCr-EES) followed by 12 months DAPT in patients undergoing PCI of unprotected left main coronary artery (LMCA) disease.
Methods
This is a multicentre randomised clinical trial study in patients with an indication for coronary artery revascularisation who have been accepted for PCI for LMCA disease after Heart Team consultation. Patients were randomly assigned in a 1:1 ratio to receive either the BP-PtCr-EES or the DP-CoCr-EES. The primary endpoint was a non-inferiority comparison of the rate of major adverse cardiovascular events (MACE), defined as all-cause death, myocardial infarction, or ischaemia-driven target vessel revascularisation at 2 years.
Results
Between December 2014 and October 2016, 818 patients (410 BP-PtCr-EES and 408 DP-CoCr-EES) were enrolled at 29 centres in Europe. At 2 years, the primary endpoint of MACE occurred in 59 patients (14.6%) in the BP-PtCr-EES group and 45 patients (11.4%) in the DP-CoCr-EES group; 1-sided upper 95% confidence interval (CI) 7.18%; p=0.04 for non-inferiority; p=0.17 for superiority. The secondary endpoint event of BARC 3 or 5 bleeding occurred in 11 patients (2.7%) in the BP-PtCr-EES group and 2 patients (0.5%) in the DP-CoCr-EES group (p=0.02).
Conclusions
In patients undergoing PCI of LMCA disease, after two years of follow-up, the use of a BP-PtCr-EES with 4 months of DAPT was non-inferior to a DP-CoCr-EES with 12 months of DAPT with respect to the composite endpoint of all-cause death, myocardial infarction or ischaemia-driven target vessel revascularisation.
Introduction
Randomised clinical trials of surgical and percutaneous revascularisation in patients with significant stenosis of an unprotected left main coronary artery (LMCA) have shown that percutaneous coronary intervention (PCI) with drug-eluting stents (DES) has comparable clinical outcomes to bypass surgery in terms of death, all myocardial infarction and stroke, but a higher rate of repeat revascularisation and non-periprocedural myocardial infarction1,2,3. As such, PCI is an acceptable alternative therapy for patients with LMCA disease, especially for those considered unsuitable for surgery due to advanced age or multiple comorbidities. Given the potentially catastrophic consequences of stent thrombosis in the LMCA, 12 months of dual antiplatelet therapy (DAPT) is reasonable. Biodegradable polymer (BP)-coated DES were developed to decrease the risk of durable polymer (DP)-related delayed vascular healing, potentially reducing the risk of stent thrombosis and allowing a shorter duration of DAPT4,5. Additionally, during PCI of LMCA disease, a large size discrepancy exists between the proximal and distal segments of the left main bifurcation and represents a potential substrate for strut malapposition. Therefore, the ability to over-expand a stent whilst maintaining radial strength is also an important consideration. A novel BP-coated platinum-chromium everolimus-eluting stent (BP-PtCr-EES) combines these features and may offer advantages for PCI in the LMCA6,7. To test this hypothesis, the Improved Drug-Eluting stent for All-comers Left Main (IDEAL-LM) study investigated clinical outcomes after BP-PtCr-EES implantation followed by only 4 months of DAPT compared to durable polymer cobalt-chromium everolimus-eluting stent (DP-CoCr-EES) implantation followed by 12 months of DAPT for treatment of unprotected LMCA disease.
Methods
Study design and patient population
The IDEAL-LM study is an investigator-initiated, international, multicentre, open-label randomised clinical trial comparing two stent designs coupled with two different durations of DAPT for PCI in LMCA disease. Patients had an indication for revascularisation according to current guidelines (LMCA >90% diameter stenosis or >50% diameter stenosis with documented ischaemia)8. PCI should be the revascularisation method of choice after discussion with the Heart Team. Patients with chronic and acute coronary syndromes were enrolled, excluding those with ST-elevation myocardial infarction within the prior 5 days. The complete inclusion and exclusion criteria are listed in Supplementary Table 1. Patients were randomly assigned in a 1:1 ratio to undergo PCI with either a BP-PtCr-EES followed by 4 months of DAPT or a DP-CoCr-EES followed by 12 months of DAPT. The use of intravascular ultrasound to optimise stent deployment was strongly recommended. Details of the main study design have been published9. All patients provided written consent before any study-specific procedures. Randomisation was performed immediately before the index procedure using web-based software (e-DREAM system; Diagram B.V.) with random blocks according to centre. Clinical follow-up was performed at discharge, 3 months, 6 months, 1 year and then annually through to 5 years. There was a prespecified substudy in 100 patients at 5 sites to assess vascular healing after 3 months using optical coherence tomography (OCT).
The study was initiated by the principal investigators and the protocol developed in consultation with the statistical committee. Boston Scientific provided funding, reviewed the protocol and participated in site selection but were not involved in any other aspect of the conduct of the study. Site monitoring, database management and statistical analyses were performed by the independent organisations listed in Supplementary Table 2. The study was approved by local institutional review boards, it adheres to the principles of the Declaration of Helsinki and Good Clinical Practice, and was registered at ClinicalTrials.gov (NCT02303717) before inclusion of the first patient.
Study device
The BP-PtCr-EES (Synergy; Boston Scientific) has a platinum-chromium alloy platform with a strut thickness of 74-81 μm and a 4 μm thick coating on the abluminal side only of a biodegradable polymer (DL-lactide-coglycolide) which is hydrolysed to carbon dioxide and water over a period of 120 days. The polymer is mixed with an everolimus to give a dose equivalent of 1 μg/mm2 and is released over a period of 90 days. The DP-CoCr-EES (XIENCE; Abbot Vascular) has a cobalt-chromium alloy platform with a strut thickness of 81 μm and an 8 μm thick durable polymer coating. The polymer is polyvinylidene fluoride hexafluoropropylene and is loaded with everolimus10.
Procedural characteristics
PCI for LMCA was performed according to the standard procedures. For LMCA bifurcation lesions, provisional stenting with side branch opening was the preferred approach, but two-stent strategies, such as T and protrusion, culotte and crush were all acceptable. Any additional non-left main lesions undergoing PCI were to be treated with the same stent to which the patient had been assigned at randomisation. If a staged procedure was planned, treatment of the non-target vessel should have been performed within 30 days, again using the same stent type as the study stent. All procedural complications and adverse events were recorded throughout the PCI procedure and the follow-up period. Cardiac biomarkers (CK-MB or troponin) were measured before and at least 4 hours post-procedure.
Objectives and endpoints
The primary objective of the trial is to establish the non-inferiority of the BP-PtCr-EES group relative to the DP-CoCr-EES group for the composite primary endpoint of major adverse cardiac events (MACE), defined as all-cause death, myocardial infarction, and ischaemia-driven target vessel revascularisation (TVR) at 2 years. Secondary endpoints included individual components of the primary endpoint, a device-oriented composite endpoint (DOCE), defined as cardiac death, myocardial infarction not clearly attributable to a non-treated vessel and clinically-indicated target lesion revascularisation (TLR), stent thrombosis as per Academic Research Consortium criteria and bleeding as per Bleeding Academic Research Consortium criteria (BARC 1 to 5 and combined BARC 3 or 5)11. Procedural success was defined as attainment of a <30% diameter stenosis of the target lesion with no in-hospital DOCE. An independent Clinical Endpoint Committee adjudicated all study endpoints including bleeding events.
Statistical analysis
The trial was powered to assess non-inferiority for the primary endpoint at 2 years post-procedure. Reviewing event rates from published data, the primary endpoint rates at 2 years for both treatment groups were predicted to be 20%12,13. Based on a prespecified absolute difference of 7.5% for the non-inferiority margin and a two-sided type I error of 0.05, a total of 818 patients provided 85% power. Non-inferiority would be shown if the upper limit of the 1-sided 95% confidence interval (CI) of the absolute risk difference was less than the non-inferiority margin of 7.5%. If non-inferiority was established, superiority testing would be performed, as well as calculation of 2-sided 95% CIs, both applied to the intention-to-treat population. Continuous variables are reported using descriptive statistics and compared using Wilcoxon’s rank sum or Student's t-tests. Categorical variables are expressed as frequency (%) and compared using the likelihood-ratio chi-square or Fisher’s exact tests. All statistical tests were interpreted at a 2-sided significance level of 0.05 and all CIs at a 2-sided level of 95% unless otherwise stated. Statistical analyses were performed by using SAS (version 9.4, SAS Institute Inc.).
Results
Baseline patient characteristics and follow-up
Between December 2014 and October 2016, 818 patients undergoing PCI for LMCA were randomly assigned to receive either BP-PtCr-EES (410 patients) or DP-CoCr-EES (408 patients). The study flow chart is presented in the Central illustration. Baseline clinical characteristics were well balanced between the groups and are shown in Table 1. Participants were mainly male (79.6%), with a mean age of 66.4±10.3 years, 22.0% had diabetes, 33.1% had previous PCI and 40.5% presented with an acute coronary syndrome. All patients received at least a short term of DAPT post-procedure and, according to the protocol, a major shift in DAPT usage was in the period from 4 months to 12 months (Supplementary Figure 1).
Central illustration. Study profile.
BP-PtCr-EES: biodegradable polymer platinum-chromium everolimus-eluting stent; DAPT: dual antiplatelet therapy; DP-CoCr-EES: durable polymer cobalt-chromium everolimus-eluting stent
Table 1. Patient baseline characteristics.
| Characteristic | BP-PtCr-EES (n=410) | DP-CoCr-EES (n=408) | Total (n=818) |
|---|---|---|---|
| Patient measures | |||
| Age (years) | 66.8±10.2 | 66.0±10.5 | 66.4±10.3 |
| Male | 338/410 (82.4) | 313/408 (76.7) | 651/818 (79.6) |
| Body mass index (kg/m2) | 28.1±4.8 | 28.6±5.2 | 28.3±5.0 |
| Current smoker | 86/410 (21.0) | 94/408 (23.0) | 180/818 (22.0) |
| Diabetes mellitus | 87/410 (21.2) | 93/408 (22.8) | 180/818 (22.0) |
| Hypertension | 315/410 (76.8) | 308/408 (75.5) | 623/818 (76.2) |
| Hypercholesterolaemia | 319/410 (77.8) | 293/408 (71.8) | 612/818 (74.8) |
| Family history of coronary artery disease | 146/410 (35.6) | 166/408 (40.7) | 312/818 (38.1) |
| Previous ACS | 163/409 (39.9) | 155/407 (38.1) | 318/816 (39.0) |
| Previous PCI | 150/410 (36.6) | 121/408 (29.7) | 271/818 (33.1) |
| Previous CABG | 29/410 (7.1) | 29/408 (7.1) | 58/818 (7.1) |
| Previous cerebrovascular accident | 34/410 (8.3) | 31/408 (7.6) | 65/818 (8.0) |
| Clinical presentation | |||
| Stable coronary artery disease | 243/410 (59.3) | 244/408 (59.8) | 487/818 (59.5) |
| Acute coronary syndrome | 167/410 (40.7) | 164/408 (40.2) | 331/818 (40.5) |
| Unstable angina | 30/410 (7.3) | 33/408 (8.1) | 63/818 (7.7) |
| Non-ST-elevation MI | 59/410 (14.4) | 69/408 (16.9) | 128/818 (15.7) |
| ST-elevation MI | 78/410 (19.0) | 62/408 (15.2) | 140/818 (17.1) |
| Data are mean±SD or counts (percentage). ACS: acute coronary syndrome; BP-PtCr-EES: biodegradable polymer platinum-chromium everolimus-eluting stent; CABG: coronary artery bypass graft; CAD: coronary artery disease; DP-CoCr-EES: durable polymer cobalt-chromium everolimus-eluting stent; MI: myocardial infarction; PCI: percutaneous coronary intervention | |||
Lesion and procedural characteristic
Lesion and procedural characteristics are summarised in Table 2. PCI for LMCA disease was performed in all patients. Isolated LMCA disease was present in 23.2% (95/410) of patients in the BP-PtCr-EES group and 25.5% (104/408) in the DP-CoCr-EES group. The SYNTAX score was 21.6±9.0 in the BP-PtCr-EES group and 20.9±9.1 in the DP-CoCr-EES group. Intravascular ultrasound was used in 39.5% and 42.2% of patients, respectively. Single-stent implantation was performed in the LMCA in 77.3% (317/410) and 81.8% (334/408) of patients in the BP-PtCr-EES and DP-CoCr-EES groups, respectively. Almost all patients (99.5%) received the assigned stent in the culprit lesion.
Table 2. Angiographic and procedural characteristics.
| BP-PtCr-EES (n=410) | DP-CoCr-EES (n=408) | p-value | ||
|---|---|---|---|---|
| PCI procedure performed | 410/410 (100.0%) | 408/408 (100.0%) | 1.00 | |
| Access site | Radial | 335/410 (81.7%) | 334/408 (81.9%) | 0.826 |
| Femoral | 70/410 (17.1%) | 69/408 (16.9%) | ||
| Brachial | 5/410 (1.2%) | 5/408 (1.2%) | ||
| Number of diseased vessels | Left main only | 95/410 (23.2%) | 104/408 (25.5%) | 0.469 |
| Left main+one vessel disease | 171/410 (41.7%) | 175/408 (42.9%) | ||
| Left main+two vessel disease | 106/410 (25.9%) | 87/408 (21.3%) | ||
| Left main+three vessel disease | 38/410 (9.2%) | 42/408 (10.3%) | ||
| SYNTAX Score | 21.6±9.0 | 20.9±9.1 | 0.310 | |
| Predilatation performed | 301/410 (73.4%) | 303/408 (74.3%) | 0.811 | |
| Post-dilatation performed | 363/410 (88.5%) | 361/408 (88.5%) | 1.00 | |
| Largest balloon size | 4.3±0.6 | 4.2±0.6 | 0.351 | |
| Maximum pressure used (atm) | 17.0±3.6 | 16.8±3.8 | 0.660 | |
| Number of stents used | 1.3±0.6 | 1.2±0.5 | 0.148 | |
| Number of stents used in the left main | 1 | 317/410 (77.3%) | 334/408 (81.8%) | 0.346 |
| 2 | 76/410 (18.5%) | 59/408 (14.5%) | ||
| Number of stents used outside left main | 1.2±0.6 | 1.1±0.5 | 0.1319 | |
| IVUS performed post-procedure | 162/410 (39.5%) | 172/408 (42.2%) | 0.476 | |
| MSA >8.5 mm2 in carina | 154/158 (97.5%) | 165/169 (97.6%) | 1.00 | |
| MSA >5.5 mm2 in both the ostium of LAD and LCx | 150/158 (94.9%) | 156/168 (92.9%) | 0.494 | |
| Procedure success | 410/410 (100.0%) | 407/408 (99.7%) | 1.00 | |
| IABP support | 2/410 (0.5%) | 2/408 (0.5%) | 0.895 | |
| DAPT at discharge | Clopidogrel | 259/410 (63.2%) | 263/407 (64.6%) | |
| Ticagrelor | 52/410 (12.7%) | 60/407 (14.7%) | ||
| Prasugrel | 28/410 (6.8%) | 29/407 (7.1%) | ||
| Monotherapy (±[N]OAC) | 69/410 (16.8%) | 53/407 (13.0%) | ||
| OAC | 21/410 (5.1%) | 27/408 (6.6%) | ||
| Data are mean±SD or counts (percentage). BP-PtCr-EES: biodegradable polymer platinum-chromium everolimus-eluting stent; DAPT: dual antiplatelet therapy; DP-CoCr-EES: durable polymer cobalt-chromium everolimus-eluting stent; IABP: intra-aortic balloon counterpulsation; IVUS: intravascular ultrasound; LAD: left anterior descending artery; LCx: left circumflex artery; MSA: minimal stent area; (N)OAC: (novel) oral anticoagulants; PCI: percutaneous coronary intervention | ||||
Clinical outcomes
At 2 years, the primary endpoint of MACE occurred in 59 patients (14.6%) in the BP-PtCr-EES group and 45 patients (11.4%) in the DP-CoCr-EES group (Table 3, Figure 1); 1-sided upper 95% CI 7.18%, p=0.04 for non-inferiority; p=0.17 for superiority. Rates of all-cause death (BP-PtCr-EES vs DP-CoCr-EES: 5.2% vs 5.3%; log-rank p=0.96), myocardial infarction (BP-PtCr-EES vs DP-CoCr-EES: 6.0% vs 3.5%; log-rank p=0.08) and ischaemia-driven TVR (BP-PtCr-EES vs DP-CoCr-EES: 7.4% vs 4.8%; log-rank p=0.15) did not significantly differ between groups through 2 years of follow-up. Rates of definite or probable stent thrombosis were not significantly different between groups (BP-PtCr-EES vs DP-CoCr-EES: 2.7% vs 1.3%; log-rank p=0.14). BARC 3 or 5 bleeding occurred in 11 (2.7%) patients assigned to the BP-PtCr-EES and 2 (0.5%) patients assigned to the DP-CoCr-EES (log-rank p=0.02) (Table 3, Figure 2). Of the 11 events in the BP-PtCr-EES group, 7 occurred when the patients were off DAPT and 4 occurred in patients also taking oral anticoagulant therapy (2 on-DAPT and 2 off-DAPT). There was no evidence for any treatment-by-subgroup interaction with respect to MACE across all prespecified subgroups (Figure 3). Landmark analyses up to 4 months, from 4 months to 1 year, and from 1 to 2 years showed no significant differences between groups with respect to MACE (Supplementary Figure 2).
Table 3. Clinical outcomes at 2 years after stent implantation.
| BP-PtCr-EES (n=410) | DP-CoCr-EES (n=408) | Risk difference (95% CI) | p-value | |
|---|---|---|---|---|
| Primary outcome | ||||
| MACE* | 14.6% (59/403) | 11.4% (45/396) | 3.28 (–1.38-7.93) | 0.1734 |
| Separate endpoints for the primary outcomes | ||||
| All-cause death | 5.2% (21/403) | 5.3% (21/396) | –0.09 (–3.19-3) | 1.0000 |
| All MI | 6.0% (24/403) | 3.5% (14/396) | 2.42 (–0.52-5.36) | 0.1343 |
| Ischaemia-driven TVR | 7.4% (30/403) | 4.8% (19/396) | 2.65 (–0.67-5.96) | 0.1404 |
| Secondary outcomes | ||||
| DOCE** | 11.9% (48/403) | 9.6% (38/396) | 2.31 (–1.98-6.61) | 0.3060 |
| Cardiac death | 3.7% (15/403) | 3.5% (14/396) | 0.19 (–2.41-2.78) | 1.0000 |
| Periprocedural MI | 2.2% (9/403) | 1.8% (7/396) | 0.47 (–1.47-2.41) | 0.8017 |
| Spontaneous MI | 4.0% (16/403) | 1.8% (7/396) | 2.2 (–0.1-4.51) | 0.0887 |
| Ischaemia-driven TLR | 6.0% (24/403) | 4.6% (18/396) | 1.41 (–1.68-4.5) | 0.4291 |
| Left main+5 mm | 5.7% (23/403) | 3.3% (13/396) | 2.42 (–0.44-5.29) | 0.1243 |
| Thrombosis endpoints | ||||
| Definite or probable stent thrombosis | 2.7% (11/403) | 1.3% (5/396) | 1.47 (–0.47-3.4) | 0.2058 |
| Acute (≤24 hours) | 0.5% (2/403) | 0.3% (1/396) | 0.24 (–0.6-1.09) | 1.0000 |
| Subacute (>24 hours to 30 days) | 1.2% (5/403) | 1.0% (4/396) | 0.23 (–1.23-1.69) | 1.0000 |
| Late (30 days to 1 year) | 0.0% (0/403) | 0.0% (0/396) | – | – |
| Very late (>1 year) | 0.99% (4/403) | 0.0% (0/396) | 0.99 (0.02-1.96) | 0.1241 |
| Bleeding endpoints | ||||
| BARC 2 | 1.2% (5/403) | 0.3% (1/396) | 0.99 (–0.2-2.18) | 0.2171 |
| BARC 3 | 2.2% (9/403) | 0.5% (2/396) | 1.73 (0.13-3.33) | 0.0637 |
| 3a | 1.2% (5/403) | 0.3% (1/396) | 0.99 (–0.2-2.18) | 0.2171 |
| 3b | 0.5% (2/403) | 0.3% (1/396) | 0.24 (–0.6-1.09) | 1.0000 |
| 3c | 0.5% (2/403) | 0.0% (0/396) | 0.50 (–0.19-1.18) | 0.4994 |
| BARC 5 | 0.7% (3/403) | 0.0% (0/396) | 0.74 (–0.09-1.58) | 0.2491 |
| 5a | 0.3% (1/403) | 0.0% (0/396) | 0.25 (–0.24-0.73) | 1.0000 |
| 5b | 0.5% (2/403) | 0.0% (0/396) | 0.5 (–0.19-1.18) | 0.4994 |
| BARC 3 or 5 bleeding | 2.7% (11/403) | 0.5% (2/396) | 2.22 (0.49-3.96) | 0.0215 |
| Data are percentage (counts). *All-cause death, myocardial infarction or ischaemia-driven TVR. **Cardiac death, target vessel myocardial infarction, or ischaemia-driven TLR. BARC: Bleeding Academic Research Consortium criteria; BP-PtCr-EES: biodegradable polymer platinum-chromium everolimus-eluting stent; CI: confidence interval; DP-CoCr-EES: durable polymer cobalt-chromium everolimus-eluting stent; MI: myocardial infarction; TLR: target lesion revascularisation; TVR: target vessel revascularisation | ||||
Figure 1. Cumulative event-free survival plot for primary endpoint over 2 years of follow-up.
ARC: Academic Research Consortium; BP-PtCr-EES: biodegradable polymer platinum-chromium everolimus-eluting stent; DAPT: dual antiplatelet therapy; DP-CoCr-EES: durable polymer cobalt-chromium everolimus-eluting stent; MACE: major adverse cardiovascular events
Figure 2. Cumulative event-free survival plot for secondary endpoint over 2 years of follow-up.
ARC: Academic Research Consortium; BARC: Bleeding Academic Research Consortium; BP-PtCr-EES: biodegradable polymer platinum-chromium everolimus-eluting stent; DAPT: dual antiplatelet therapy; DP-CoCr-EES: durable polymer cobalt-chromium everolimus-eluting stent; MACE: major adverse cardiovascular events; MI: myocardial infarction; TVR: target vessel revascularisation
Figure 3. Stratified analyses of the primary endpoint at 2 years across subgroups.
* p-value is the test of interaction between treatment and subgroup, unadjusted for multiplicity. ACS: acute coronary syndrome; CI: confidence interval; DAPT: dual antiplatelet therapy; HR: hazard ratio; IVUS: intravascular ultrasound
Discussion
In this all-comers, multicentre, single-blind, randomised clinical trial, LMCA PCI with BP-PtCr-EES followed by 4 months of DAPT was non-inferior to DP-CoCr-EES followed by 12 months of DAPT in terms of MACE at 2 years. No significant differences were documented in the individual components of the primary endpoint, but they all trended numerically higher in the BP-PtCr-EES with 4-month DAPT group than in the DP-CoCr-EES with 12-month DAPT group. The rates of definite and probable stent thrombosis were low and did not differ between groups. Counterintuitively, BARC 3 or 5 bleeding occurred more commonly in the short-duration DAPT group but the study was not powered to show a difference in bleeding events and so this could be the play of chance. Moreover, all 4 patients who experienced BARC 3-5 bleeding whilst taking an oral anticoagulant were in the BP-PtCr-EES group.
The specific design of the BP-PtCr-EES platform, as well as the polymer degradation kinetics, has been reported to provide favourable vascular healing in non-LMCA lesions, with rates of strut coverage and apposition at 3 months of 94.5% and 93.8%, respectively14. In the TRANSFORM-OCT (TRiple Assessment of Neointima Stent FOrmation to Reabsorbable polyMer With Optical Coherence Tomography) study, BP-PtCr-EES and DP-zotarolimus-eluting stents showed a similar healing response at 3 months15. The OCT substudy of the IDEAL-LM study showed similar and near complete vascular healing with both stents 3 months after implantation, with a strut coverage >20 μm for over 96% of the individual struts16. These findings support the view that the biodegradable and durable polymers utilised in contemporary DES are associated with favourable vascular healing, even in LMCA disease. Nevertheless, little is known about the efficacy and safety of a short duration of DAPT after PCI with contemporary DES in LMCA. Current guidelines from the ACC/AHA recommend at least 6-12 months of DAPT in patients undergoing PCI with DES17. The European Society of Cardiology Guidelines recommend a 3-month period of DAPT in patients at high bleeding risk (e.g., PRECISE-DAPT score ≥25) undergoing PCI for stable coronary artery disease18. The European Bifurcation Club recently consulted worldwide opinion leaders for a detailed DAPT strategy proposal involving bleeding risk, patient characteristics and procedural characteristics, such as imaging guidance and bifurcation approach19.
Recently, several large-scale randomised trials investigated the efficacy and safety of a short duration of DAPT (1 to 3 months) after PCI in specific study populations (e.g., all-comers, elderly, or high risk for bleeding or an ischaemic event)20,21,22. Overall, a short duration of DAPT after PCI did not increase the incidence of ischaemic events and may reduce the risk of bleeding events. Nevertheless, it is noteworthy that only a small proportion of patients (from 1.8% to 8.2%) with LMCA disease were included in the aforementioned studies. Although no significant differences were observed in the ischaemic endpoints in IDEAL-LM, they all trended numerically higher in the BP-PtCr-EES/short DAPT group and bleeding was not reduced. Accordingly, the risks and benefits of a short duration of DAPT after PCI for LMCA disease need to be further investigated, taking into account the personalised risk of bleeding and ischaemic events.
In the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, PCI with the same DP-CoCr-EES used in IDEAL-LM, coupled with a minimum of 12 months of DAPT, was non-inferior to CABG at 5 years with respect to a composite endpoint of all-cause death, stroke, or myocardial infarction2. The SYNTAX scores and the incidence of diabetes were similar in EXCEL to the patient population in IDEAL-LM. Continuation of DAPT beyond 1 year in EXCEL did not reduce the rate of death, myocardial infarction or stroke23.
In a patient-level pooled analysis of five multicentre registries including 700 patients treated for LMCA disease, the rate of target lesion failure in patients treated with two-stent techniques was significantly higher than in the one-stent group only when DAPT was interrupted before 1 year24. In IDEAL-LM, approximately 80% of patients underwent LMCA-PCI using a single-stent technique and we did not see an interaction between treatment with one or more stents and randomised treatment allocation.
Study limitations
Firstly, the observed rates of the primary endpoint were lower than predicted, with the difference being due to lower rates of all-cause death and ischaemia-driven TVR than in previous studies12,13,25,26,27. As a specific example, all-cause death at two years was 5.0% in IDEAL-LM, compared to 10.0% in the ISAR-LEFT-MAIN study28. Generally, of course, this is good news for patients undergoing LMCA-PCI, but it means that the result of IDEAL-LM is not particularly robust. The predicted event rate of 20% in both groups coupled with an absolute non-inferiority margin of 7.5% yield a relative non-inferiority margin of 7.5/20=0.375. This is similar to the EXCEL trial in which the predicted event rates were 11% in both groups (excluding repeat revascularisation) with a non-inferiority margin of 4.2%, yielding a relative non-inferiority margin of 4.2/11=0.38. If we apply this to the observed event rates in IDEAL-LM, the equivalent absolute non-inferiority margin would be 4.3% and non-inferiority would not be confirmed. Alternatively, and retrospectively, one can state that due to the lower-than-predicted event rates, the trial is now underpowered, though potentially the original power of 85% could be recovered during ongoing follow-up. Given the methodological limitations of the study, and the numerically higher number of events in the BP-PtCr-EES followed by 4-month DAPT group, a larger dataset is required to evaluate this potentially concerning signal.
Secondly, the IDEAL-LM study was designed to compare two therapeutic strategies for LMCA-PCI. The duration of DAPT was coupled to and determined by the randomly assigned stent type but we acknowledge that this may hinder the interpretation of any between-group differences in outcomes. Finally, the majority of patients were treated using one-stent techniques and therefore more data are required for a more robust recommendation on DAPT duration for patients treated with two-stent strategies.
Conclusions
PCI with the BP-PtCr-EES followed by 4 months of DAPT was non-inferior to the DP-CoCr-EES followed by 12 months of DAPT with respect to MACE at 2 years in an all-comers population with LMCA disease. However, due to event rates that were lower than predicted, the trial is underpowered and the individual components of MACE all trend numerically higher in the BP-PtCr-EES with 4-month DAPT group. The findings of this trial should be interpreted only as hypothesis generating. The efficacy and safety of a short duration of DAPT after LMCA PCI requires further investigation and future studies should focus on the individual patient risk for bleeding and ischaemic events.
Data sharing
All data, including study participant data, data dictionary, statistical analysis plan, and informed consent, will not be shared.
Impact on daily practice
PCI for left main disease is frequently a primary strategy due to relative contraindications for bypass surgery. Stent design iterations intend to improve outcomes and minimise antiplatelet therapy for these patients where comorbidity is frequently present. This study demonstrated that a strategy of using a biodegradable polymer-coated platinum-chromium everolimus-eluting stent followed by four months of dual antiplatelet therapy was non-inferior to a strategy with a durable polymer-coated cobalt-chromium everolimus-eluting stent followed by 12 months dual antiplatelet therapy. Superiority in bleeding events was not achieved. As the overall event rate was low, this study cannot make definite conclusions, yet both strategies provided state-of-the-art outcomes.
Supplementary data
Endpoint definitions.
CONSORT 2010 checklist.
Inclusion and exclusion criteria.
Study organisations.
Number of patients randomised per site.
DAPT usage from 0 to 24 months.
Landmark analysis for primary endpoint over 2 years of follow-up.
Acknowledgments
Acknowledgements
All authors are indebted to Mrs. Colette Donaghy (Venn Life Sciences, Belfast, United Kingdom) and Mrs. Evelien Kolkman (Diagram, Zwolle, the Netherlands) for their assistance in coordinating the trial.
Conflict of interest statement
R. van Geuns reports receiving grants and personal fees from Boston Scientific, during the conduct of the study; grants and personal fees from Abbott Vascular, AstraZeneca, and Amgen; and personal fees from Sanofi, outside the submitted work. M. Lesiak has received speaker’s honoraria from Abbott Vascular, and Boston Scientific. Y. Onuma was an advisory board member of Abbott Vascular. M.B. McEntegart has a proctoring agreement with Boston Scientific and Vascular Perspectives. K.G. Oldroyd reports receiving grant support and lecture fees from AstraZeneca and lecture fees from Biosensors, Abbott Vascular, and GE. The other authors have no conflicts of interest to declare.
Abbreviations
- BARC
Bleeding Academic Research Consortium criteria
- BP
biodegradable polymer
- CoCr-EES
cobalt-chromium everolimus-eluting stent
- DAPT
dual antiplatelet therapy
- DES
drug-eluting stent
- DOCE
device-oriented composite endpoint
- DP
durable polymer
- IDEAL-LM
Improved Drug-Eluting stent for All-comers Left Main
- LMCA
left main coronary artery
- MACE
major adverse cardiac events
- OCT
optical coherence tomography
- PCI
percutaneous coronary intervention
- TLR
target lesion revascularisation
- TVR
target vessel revascularisation
- PtCr-EES
platinum-chromium everolimus-eluting stent
Contributor Information
Robert-Jan van Geuns, Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Cardiology, Thorax Center, Erasmus Medical Center, Rotterdam, the Netherlands.
Chang Chun-Chin, Department of Cardiology, Thorax Center, Erasmus Medical Center, Rotterdam, the Netherlands; Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Margaret B. McEntegart, Golden Jubilee National Hospital, Glasgow, United Kingdom.
Evgeny Merkulov, Russian Cardiology Research Center, Moscow, Russian Federation.
Evgeny Kretov, E.N. Meshalkin National Medical Research Center, Novosibirsk, Russian Federation.
Maciej Lesiak, 1st Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland.
Peter O’Kane, Department of Cardiology, Royal Bournemouth Hospital, Bournemouth, United Kingdom.
Colm G. Hanratty, Belfast Health and Social Care Trust, Belfast, United Kingdom.
Erwan Bressollette, Hôpital Privé du Confluent, Nantes, France.
Marc Silvestri, Clinique Axium, Aix-en-Provence, France.
Adrian Wlodarczak, Department of Cardiology, Miedziowe Centrum Zdrowia S.A., Lubin, Poland.
Paul Barragan, Department of Cardiology, Polyclinique les Fleurs, Ollioules, France.
Richard Anderson, University Hospital of Wales, Cardiff, United Kingdom.
Aleksey Protopopov, Krasnoyarsk Regional Vascular Centre, Krasnoyarsk, Russia.
Aaron Peace, Altnagelvin Hospital, Londonderry, United Kingdom.
Ian Menown, Craigavon Area Hospital, Craigavon, United Kingdom.
Paul Rocchiccioli, Golden Jubilee National Hospital, Glasgow, United Kingdom.
Yoshinobu Onuma, Department of Cardiology, Thorax Center, Erasmus Medical Center, Rotterdam, the Netherlands; Cardialysis, Rotterdam, the Netherlands.
Keith G. Oldroyd, Golden Jubilee National Hospital, Glasgow, United Kingdom.
References
- Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Ståhle E, Feldman TE, van den, Bass EJ, Van Dyck, Leadley K, Dawkins KD, Mohr FW SYNTAX Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961–72. doi: 10.1056/NEJMoa0804626. [DOI] [PubMed] [Google Scholar]
- Stone GW, Sabik JF, Serruys PW, Simonton CA, Généreux P, Puskas J, Kandzari DE, Morice MC, Lembo N, Brown WM, Taggart DP, Banning A, Merkely B, Horkay F, Boonstra PW, van Boven, Ungi I, Bogats G, Mansour S, Noiseux N, Sabate M, Pomar J, Hickey M, Gershlick A, Buszman P, Bochenek A, Schampaert E, Page P, Dressler O, Kosmidou I, Mehran R, Pocock SJ, Kappetein AP EXCEL Trial Investigators. Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease. N Engl J Med. 2016;375:2223–35. doi: 10.1056/NEJMoa1610227. [DOI] [PubMed] [Google Scholar]
- Mäkikallio T, Holm NR, Lindsay M, Spence MS, Erglis A, Menown IB, Trovik T, Eskola M, Romppanen H, Kellerth T, Ravkilde J, Jensen LO, Kalinauskas G, Linder RB, Pentikainen M, Hervold A, Banning A, Zaman A, Cotton J, Eriksen E, Margus S, Sorensen HT, Nielsen PH, Niemelä M, Kervinen K, Lassen JF, Maeng M, Oldroyd K, Berg G, Walsh SJ, Hanratty CG, Kumsars I, Stradins P, Steigen TK, Fröbert O, Graham AN, Endresen PC, Corbascio M, Kajander O, Trivedi U, Hartikainen J, Anttila V, Hildick-Smith D, Thuesen L, Christiansen EH NOBLE study investigators. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. Lancet. 2016;388:2743–52. doi: 10.1016/S0140-6736(16)32052-9. [DOI] [PubMed] [Google Scholar]
- Serruys PW, Farooq V, Kalesan B, de Vries, Buszman P, Linke A, Ischinger T, Klauss V, Eberli F, Wijns W, Morice MC, Di Mario, Corti R, Antoni D, Sohn HY, Eerdmans P, Rademaker-Havinga T, van Es, Meier B, Jüni P, Windecker S. Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial. JACC Cardiovasc Interv. 2013;6:777–89. doi: 10.1016/j.jcin.2013.04.011. [DOI] [PubMed] [Google Scholar]
- Hagiwara H, Hiraishi Y, Terao H, Hirai T, Sakaoka A, Sasaki M, Murota S, Inoue K, Kimura J. Vascular responses to a biodegradable polymer (polylactic acid) based biolimus A9-eluting stent in porcine models. EuroIntervention. 2012;8:743–51. doi: 10.4244/EIJV8I6A114. [DOI] [PubMed] [Google Scholar]
- Ng J, Foin N, Ang HY, Fam JM, Sen S, Nijjer S, Petraco R, Di Mario, Davies J, Wong P. Over-expansion capacity and stent design model: An update with contemporary DES platforms. Int J Cardiol. 2016;221:171–9. doi: 10.1016/j.ijcard.2016.06.097. [DOI] [PubMed] [Google Scholar]
- Fam JM. Defining optimal stent overexpansion strategies for left main stenting: insights from bench testing. AsiaIntervention. 2017;3:110–20. [Google Scholar]
- Authors/Task Force, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35:2541–619. doi: 10.1093/eurheartj/ehu278. [DOI] [PubMed] [Google Scholar]
- Lemmert ME, Oldroyd K, Barragan P, Lesiak M, Byrne RA, Merkulov E, Daemen J, Onuma Y, Witberg K, van Geuns. Reduced duration of dual antiplatelet therapy using an improved drug-eluting stent for percutaneous coronary intervention of the left main artery in a real-world, all-comer population: Rationale and study design of the prospective randomized multicenter IDEAL-LM trial. Am Heart J. 2017;187:104–11. doi: 10.1016/j.ahj.2017.02.015. [DOI] [PubMed] [Google Scholar]
- Saez A, Moreno R. Everolimus-eluting coronary stents. Med Devices (Auckl) 2010;3:51–6. doi: 10.2147/MDER.S4422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123:2736–47. doi: 10.1161/CIRCULATIONAHA.110.009449. [DOI] [PubMed] [Google Scholar]
- Mehilli J, Kastrati A, Byrne RA, Bruskina O, Iijima R, Schulz S, Pache J, Seyfarth M, Massberg S, Laugwitz KL, Dirschinger J, Schömig A LEFT-MAIN Intracoronary Stenting and Angiographic Results: Drug-Eluting Stents for Unprotected Coronary Left Main Lesions Study Investigators. Paclitaxel- versus sirolimus-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol. 2009;53:1760–8. doi: 10.1016/j.jacc.2009.01.035. [DOI] [PubMed] [Google Scholar]
- Park DW, Seung KB, Kim YH, Lee JY, Kim WJ, Kang SJ, Lee SW, Lee CW, Park SW, Yun SC, Gwon HC, Jeong MH, Jang YS, Kim HS, Kim PJ, Seong IW, Park HS, Ahn T, Chae IH, Tahk SJ, Chung WS, Park SJ. Long-term safety and efficacy of stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry. J Am Coll Cardiol. 2010;56:117–24. doi: 10.1016/j.jacc.2010.04.004. [DOI] [PubMed] [Google Scholar]
- de la, Tejedor P, Camarero TG, Duran JM, Lee DH, Monedero J, Laso FS, Calderon MA, Veiga G, Zueco J. Early healing assessment with optical coherence tomography of everolimus-eluting stents with bioabsorbable polymer (synergy™) at 3 and 6 months after implantation. Catheter Cardiovasc Interv. 2016;88:E67–73. doi: 10.1002/ccd.26299. [DOI] [PubMed] [Google Scholar]
- Guagliumi G, Shimamura K, Sirbu V, Garbo R, Boccuzzi G, Vassileva A, Valsecchi O, Fiocca L, Canova P, Colombo F, Tensol Rodriguez, Nakamura D, Attizzani GF, Cereda A, Satogami K, De Luca, Saia F, Capodanno D. Temporal course of vascular healing and neoatherosclerosis after implantation of durable- or biodegradable-polymer drug-eluting stents. Eur Heart J. 2018;39:2448–56. doi: 10.1093/eurheartj/ehy273. [DOI] [PubMed] [Google Scholar]
- Chang CC, Onuma Y, Lesiak M, Merkulov E, Anderson R, Kretov E, Barragan P, Oldroyd KG, van Geuns. Optical Coherence Tomography Assessment for Percutaneous Coronary Intervention of the Left Main Artery: The IDEAL-LM Trial. JACC Cardiovasc Interv. 2020;13:401–2. doi: 10.1016/j.jcin.2019.09.012. [DOI] [PubMed] [Google Scholar]
- Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68:1082–115. doi: 10.1016/j.jacc.2016.03.513. [DOI] [PubMed] [Google Scholar]
- Valgimigli M, Bueno H, Byrne RA?, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018;39:213–60. doi: 10.1093/eurheartj/ehx419. [DOI] [PubMed] [Google Scholar]
- Zimarino M, Angiolillo DJ, Dangas G, Capodanno D, Barbato E, Hahn JY, Giustino G, Watanabe H, Costa F, Cuisset T, Rossini R, Sibbing D, Burzotta F, Louvard Y, Shehab A, Renda G, Kimura T, Gwon HC, Chen SL, Costa RA, Koo BK, Storey RF, Valgimigli M, Mehran R, Stankovic G. Antithrombotic therapy after percutaneous coronary intervention of bifurcation lesions. EuroIntervention. 2021;17:59–66. doi: 10.4244/EIJ-D-20-00885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vranckx P, Valgimigli M, Jüni P, Hamm C, Steg PG, Heg D, van Es, McFadden EP, Onuma Y, van Meijeren, Chichareon P, Benit E, Möllmann H, Janssens L, Ferrario M, Moschovitis A, Zurakowski A, Dominici M, Van Geuns, Huber K, Slagboom T, Serruys PW, Windecker S GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018;392:940–9. doi: 10.1016/S0140-6736(18)31858-0. [DOI] [PubMed] [Google Scholar]
- Varenne O, Cook S, Sideris G, Kedev S, Cuisset T, Carrie D, Hovasse T, Garot P, El Mahmoud, Spaulding C, Helft G, Diaz Fernandez, Brugaletta S, Pinar-Bermudez E, Mauri Ferre, Commeau P, Teiger E, Bogaerts K, Sabate M, Morice MC, Sinnaeve PR SENIOR investigators. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. Lancet. 2018;391:41–50. doi: 10.1016/S0140-6736(17)32713-7. [DOI] [PubMed] [Google Scholar]
- Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, Cha JY, Collier T, Dangas G, Dudek D, Džavík V, Escaned J, Gil R, Gurbel P, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Marx SO, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Sartori S, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019;381:2032–42. doi: 10.1056/NEJMoa1908419. [DOI] [PubMed] [Google Scholar]
- Brener SJ, Serruys PW, Morice MC, Mehran R, Kappetein AP, Sabik JF, Liu Y, Dressler O, Ben-Yehuda O, Stone GW. Optimal Duration of Dual Antiplatelet Therapy After Left Main Coronary Stenting. J Am Coll Cardiol. 2018;72:2086–7. doi: 10.1016/j.jacc.2018.07.084. [DOI] [PubMed] [Google Scholar]
- Rhee TM, Park KW, Kim CH, Kang J, Han JK, Yang HM, Kang HJ, Koo BK, Kim HS. Dual Antiplatelet Therapy Duration Determines Outcome After 2- But Not 1-Stent Strategy in Left Main Bifurcation Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2018;11:2453–63. doi: 10.1016/j.jcin.2018.09.020. [DOI] [PubMed] [Google Scholar]
- Mehilli J, Richardt G, Valgimigli M, Schulz S, Singh A, Abdel-Wahab M, Tiroch K, Pache J, Hausleiter J, Byrne RA, Ott I, Ibrahim T, Fusaro M, Seyfarth M, Laugwitz KL, Massberg S, Kastrati A ISAR-LEFT-MAIN 2 Study Investigators. Zotarolimus- versus everolimus-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol. 2013;62:2075–82. doi: 10.1016/j.jacc.2013.07.044. [DOI] [PubMed] [Google Scholar]
- Kim YH, Park DW, Ahn JM, Yun SC, Song HG, Lee JY, Kim WJ, Kang SJ, Lee SW, Lee CW, Park SW, Jang Y, Jeong MH, Kim HS, Hur SH, Rha SW, Lim DS, Her SH, Seung KB, Seong IW, Park SJ PRECOMBAT-2 Investigators. Everolimus-eluting stent implantation for unprotected left main coronary artery stenosis. The PRECOMBAT-2 (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) study. JACC Cardiovasc Interv. 2012;5:708–17. doi: 10.1016/j.jcin.2012.05.002. [DOI] [PubMed] [Google Scholar]
- Morice MC, Serruys PW, Kappetein AP, Feldman TE, Stahle E, Colombo A, Mack MJ, Holmes DR, Choi JW, Ruzyllo W, Religa G, Huang J, Roy K, Dawkins KD, Mohr F. Five-year outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial. Circulation. 2014;129:2388–94. doi: 10.1161/CIRCULATIONAHA.113.006689. [DOI] [PubMed] [Google Scholar]
- Tiroch K, Mehilli J, Byrne RA, Schulz S, Massberg S, Laugwitz KL, Vorpahl M, Seyfarth M, Kastrati A ISAR-LEFT MAIN Study Investigators. Impact of coronary anatomy and stenting technique on long-term outcome after drug-eluting stent implantation for unprotected left main coronary artery disease. JACC Cardiovasc Interv. 2014;7:29–36. doi: 10.1016/j.jcin.2013.08.013. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Endpoint definitions.
CONSORT 2010 checklist.
Inclusion and exclusion criteria.
Study organisations.
Number of patients randomised per site.
DAPT usage from 0 to 24 months.
Landmark analysis for primary endpoint over 2 years of follow-up.