Search

Purpose. Pre-treatment prediction of individual blood pressure (BP) response to anti-hypertensive medication is important to determine the specific regimen for promptly and safely achieving a target BP. This study aimed to develop supervised machine learning (ML) models for predicting patient-specific treatment effects using 24-hour ambulatory BP monitoring (ABPM) data. Materials and Methods. A total of 1,129 patients who had both baseline and follow-up ABPM data were randomly assigned into training, validation and test sets in a 3:1:1 ratio. Utilising the features including clinical and laboratory findings, initial ABPM data, and anti-hypertensive medication at baseline and at follow-up, ML models were developed to predict post-treatment individual BP response. Each case was labelled by the mean 24-hour and daytime BPs derived from the follow-up ABPM. Results. At baseline, 616 (55%) patients had been treated using mono or combination therapy with 45 anti-hypertensive drugs and the remaining 513 (45%) patients had been untreated (drug-naïve). By using CatBoost, the difference between predicted vs. measured mean 24-hour systolic BP at follow-up was 8.4 ± 7.0 mm Hg (% difference of 6.6% ± 5.7%). The difference between predicted vs. measured mean 24-hour diastolic BP was 5.3 ± 4.3 mm Hg (% difference of 6.8% ± 5.5%). There were significant correlations between the CatBoost-predicted vs. the ABPM-measured changes in the mean 24-hour Systolic (r = 0.74) and diastolic (r = 0.68) BPs from baseline to follow-up. Even in the patients with renal insufficiency or diabetes, the correlations between CatBoost-predicted vs. ABPM-measured BP changes were significant. Conclusion. ML algorithms accurately predict the post-treatment ambulatory BP levels, which may assist clinicians in personalising anti-hypertensive treatment. The prediction of post-treatment BP response is essential to plan the appropriate optimal treatment strategy for achieving the target BP level.The poor predictability of the post-treatment BP level is due to the complex pathophysiology of individual BP response, which can partly explain the poor rate to achieve the target systolic BP.In this current study including both treated and untreated patients with hypertension, machine leaning models predicted the post-treatment mean BP levels on 24-hr ABPM even in high-risk patients and patients with a high BP variability.Model-derived selection and optimisation of anti-hypertension drugs may facilitate prompt achievement of adequate BP control without drug-related complications and avoiding repeating 24-hour ABPM or multiple visits for drug readjustment. The prediction of post-treatment BP response is essential to plan the appropriate optimal treatment strategy for achieving the target BP level. The poor predictability of the post-treatment BP level is due to the complex pathophysiology of individual BP response, which can partly explain the poor rate to achieve the target systolic BP. In this current study including both treated and untreated patients with hypertension, machine leaning models predicted the post-treatment mean BP levels on 24-hr ABPM even in high-risk patients and patients with a high BP variability. Model-derived selection and optimisation of anti-hypertension drugs may facilitate prompt achievement of adequate BP control without drug-related complications and avoiding repeating 24-hour ABPM or multiple visits for drug readjustment.

Despite the abundance of Electronic Healthcare Records (EHR), its heterogeneity restricts the utilization of medical data in building predictive models. To address this challenge, we propose Universal Healthcare Predictive Framework (UniHPF), which requires no medical domain knowledge and minimal pre-processing for multiple prediction tasks. Experimental results demonstrate that UniHPF is capable of building large-scale EHR models that can process any form of medical data from distinct EHR systems. Our framework significantly outperforms baseline models in multi-source learning tasks, including transfer and pooled learning, while also showing comparable results when trained on a single medical dataset. To empirically demonstrate the efficacy of our work, we conducted extensive experiments using various datasets, model structures, and tasks. We believe that our findings can provide helpful insights for further research on the multi-source learning of EHRs., Comment: Main paper (11pages)

Background and Purpose: The aim of this study was to determine the relationship between the heart rate-corrected QT (QTc) interval and the risk of incident long-term mortality in patients with acute ischemic stroke (AIS), considering the impact of sex differences on clinical characteristics, outcomes, and QTc intervals.Methods: We analyzed prospectively registered data included patients with AIS who visited the emergency room within 24 h of stroke onset and underwent routine cardiac testing, such as measurements of cardiac enzymes and 12-lead ECG. QTc interval was corrected for heart rate using Fridericia's formula and was stratified by sex-specific quartiles. Cox proportional hazards models were used to examine the association between baseline QTc interval and incident all-cause death.Results: A total of 1,668 patients with 1,018 (61.0%) men and mean age 66.0 ± 12.4 years were deemed eligible. Based on the categorized quartiles of the QTc interval, cardiovascular risk profile, and stroke severity increased with prolonged QTc interval, and the risk of long-term mortality increased over a median follow-up of 33 months. Cox proportional hazard model analysis showed that the highest quartile of QTc interval (≥479 msec in men and ≥498 msec in women; hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.07–2.08) was associated with all-cause death. Furthermore, dichotomized QTc interval prolongation, defined by the highest septile of the QTc interval (≥501 ms in men and ≥517 m in women: HR: 1.33, 95% CI: 1.00–1.80) was significantly associated with all-cause mortality after adjusting for all clinically relevant variables, such as stroke severity.Conclusions: Prolonged QTc interval was associated with increased risk of long-term mortality, in parallel with the increasing trend of prevalence of cardiovascular risk profiles and stroke severity, across sex differences in AIS patients.

In percutaneous intervention for treatment of coronary plaques, guidewire navigation is a primary procedure for stent delivery. Steering a flexible guidewire within coronary arteries requires considerable training, and the non-linearity between the control operation and the movement of the guidewire makes precise manipulation difficult. Here, we introduce a deep reinforcement learning(RL) framework for autonomous guidewire navigation in a robot-assisted coronary intervention. Using Rainbow, a segment-wise learning approach is applied to determine how best to accelerate training using human demonstrations with deep Q-learning from demonstrations (DQfD), transfer learning, and weight initialization. `State' for RL is customized as a focus window near the guidewire tip, and subgoals are placed to mitigate a sparse reward problem. The RL agent improves performance, eventually enabling the guidewire to reach all valid targets in `stable' phase. Our framework opens anew direction in the automation of robot-assisted intervention, providing guidance on RL in physical spaces involving mechanical fatigue., 15 pages, 7 figures, 3 tables

Substantial increase in the use of Electronic Health Records (EHRs) has opened new frontiers for predictive healthcare. However, while EHR systems are nearly ubiquitous, they lack a unified code system for representing medical concepts. Heterogeneous formats of EHR present a substantial barrier for the training and deployment of state-of-the-art deep learning models at scale. To overcome this problem, we introduce Description-based Embedding, DescEmb, a code-agnostic description-based representation learning framework for predictive modeling on EHR. DescEmb takes advantage of the flexibility of neural language understanding models while maintaining a neutral approach that can be combined with prior frameworks for task-specific representation learning or predictive modeling. We tested our model's capacity on various experiments including prediction tasks, transfer learning and pooled learning. DescEmb shows higher performance in overall experiments compared to code-based approach, opening the door to a text-based approach in predictive healthcare research that is not constrained by EHR structure nor special domain knowledge., Comment: Accepted at CHIL 2022. Main paper + supplementary material (21 pages, 8 figures, 12 tables)

BACKGROUND. Current clinical biomarkers for the programmed cell death 1 (PD-1) blockade therapy are insufficient because they rely only on the tumor properties, such as programmed cell death ligand 1 expression frequency and tumor mutation burden. Identifying reliable, responsive biomarkers based on the host immunity is necessary to improve the predictive values. METHODS. We investigated levels of plasma metabolites and T cell properties, including energy metabolism markers, in the blood of patients with non-small cell lung cancer before and after treatment with nivolumab (n = 55). Predictive values of combination markers statistically selected were evaluated by cross-validation and linear discriminant analysis on discovery and validation cohorts, respectively. Correlation between plasma metabolites and T cell markers was investigated. RESULTS. The 4 metabolites derived from the microbiome (hippuric acid), fatty acid oxidation (butyrylcarnitine), and redox (cystine and glutathione disulfide) provided high response probability (AUC = 0.91). Similarly, a combination of 4 T cell markers, those related to mitochondrial activation (PPARγ coactivator 1 expression and ROS), and the frequencies of CD8+PD-1hi and CD4+ T cells demonstrated even higher prediction value (AUC = 0.96). Among the pool of selected markers, the 4 T cell markers were exclusively selected as the highest predictive combination, probably because of their linkage to the abovementioned metabolite markers. In a prospective validation set (n = 24), these 4 cellular markers showed a high accuracy rate for clinical responses of patients (AUC = 0.92). CONCLUSION. Combination of biomarkers reflecting host immune activity is quite valuable for responder prediction., PD-1抗体がん免疫治療の有効性を判別するバイオマーカーを同定 --血液検査のみで有効性の診断が可能に--. 京都大学プレスリリース. 2020-01-31.

Background: The risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non‐small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI‐related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD., Methods: We retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy. The existence of ILD in these patients was determined by lung computed tomography findings; 26 patients had ILD. We evaluated the efficacy of nivolumab by measuring the response rate (RR), progression‐free survival (PFS) duration, and lung toxicity by incidence, severity, and outcome of nivolumab‐related ILD., Results: The RR and median PFS of the ILD and non‐ILD groups were 27% versus 13% (P = 0.078) and 2.7 (95% confidence interval [CI], 1.7–5.3) versus 2.9 months (95% CI 2.1–3.4; P = 0.919), respectively. The incidences of total and severe nivolumab‐related pneumonitis were significantly higher in the ILD group than in the non‐ILD group (31% vs. 12%, P = 0.014 and 19% vs. 5%, P = 0.022, respectively). No death from nivolumab‐related pneumonitis occurred. Over 50% of the patients in both groups with nivolumab‐related pneumonitis showed improvement over time., Conclusion: Relative to the non‐ILD group, nivolumab‐related pneumonitis was observed more frequently in the ILD group; however, most cases were manageable.

This study aimed to investigate the feasibility and safety of the modified balloon crush technique. The conventional crush technique accompanies difficult and suboptimal final kissing balloon inflation (FKI) In a single-center percutaneous coronary intervention registry, 515 patients with 515 bifurcation lesions were treated with the modified balloon technique (n = 70) or the conventional crush technique (n = 445). In contrast to the conventional crush technique, where the implanted side branch (SB) stent is crushed by expansion of the main branch (MB) stent, the modified balloon crush technique uses balloon crushing and additional SB ballooning across the crushed SB stent before MB stenting to facilitate FKI. The primary outcome of interest was major adverse cardiovascular event (MACE), a composite of all-cause death, spontaneous myocardial infarction, and target vessel revascularization. Baseline clinical and angiographic characteristics were similar between the 2 treatment groups. FKI had comparable success rates in both groups (97.1% for the modified balloon group and 98.4% for the conventional crush group; P = .35). There were no differences in procedure time, fluoroscopic time, or contrast amount between the 2 groups. At 1-year follow up, the cumulative MACE incidences were comparable between the 2 groups (7.3% vs 8.8%; P = .73). The incidence of target lesion revascularization (TLR) was significantly lower after the modified balloon crush technique compared with the conventional crush technique (0% vs 5.6%; P = .048). The modified balloon crush technique appears to be a feasible and safe alternative to the conventional crush technique with the potential to reduce the revascularization rate.

In this paper, we propose an effective electrocardiogram (ECG) arrhythmia classification method using a deep two-dimensional convolutional neural network (CNN) which recently shows outstanding performance in the field of pattern recognition. Every ECG beat was transformed into a two-dimensional grayscale image as an input data for the CNN classifier. Optimization of the proposed CNN classifier includes various deep learning techniques such as batch normalization, data augmentation, Xavier initialization, and dropout. In addition, we compared our proposed classifier with two well-known CNN models; AlexNet and VGGNet. ECG recordings from the MIT-BIH arrhythmia database were used for the evaluation of the classifier. As a result, our classifier achieved 99.05% average accuracy with 97.85% average sensitivity. To precisely validate our CNN classifier, 10-fold cross-validation was performed at the evaluation which involves every ECG recording as a test data. Our experimental results have successfully validated that the proposed CNN classifier with the transformed ECG images can achieve excellent classification accuracy without any manual pre-processing of the ECG signals such as noise filtering, feature extraction, and feature reduction., Submitted to journal

A 70-year-old man was admitted to our hospital with an abnormal chest X-ray shadow. Bronchoscopy revealed an adenocarcinoma tumour with an epidermal growth factor receptor (EGFR) exon 19 deletion. Positron emission tomography-computed tomography scanning and magnetic resonance imaging showed advanced stage IV lung cancer. He was treated with erlotinib as a first-line drug, which maintained a clinical response for 16 months. After disease progression, a re-biopsy was done from the tumour in the right lower lobe. The obtained specimen harboured both small-cell lung cancer (SCLC) transformation with retention of the EGFR 19 deletion and the development of an EGFR T790M mutation. We came across a very rare condition of concomitant T790M mutation and SCLC transformation after acquired resistance to EGFR-tyrosine kinase inhibitor.

OBJECTIVES The aim of this study was to compare long-term survival between patients with severe coronary artery disease undergoing coronary artery bypass grafting (CABG) and those undergoing percutaneous coronary intervention (PCI) achieving complete revascularization (CR) or incomplete revascularization. BACKGROUND The importance of CR in decision making regarding revascularization strategy in patients with severe coronary artery disease is unknown. METHODS Data were pooled from the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trials. The primary outcome was death from any cause and was compared in an as-treated analysis. RESULTS The rate of CR was 61.7% (57.2% with PCI and 66.8% with CABG). During a median 4.9-year follow-up period (interquartile range: 4.5 to 5.0 years), compared with patients undergoing CABG with CR, those undergoing PCI with incomplete revascularization had a higher risk for death from any cause (adjusted hazard ratio [aHR]: 1.43; 95% confidence interval [CI]: 1.03 to 2.00; p = 0.036) and the composite of death, myocardial infarction, and stroke (aHR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003). However, there was no significant difference between patients undergoing CABG with CR and those undergoing PCI with CR regarding the risk for death from any cause (aHR: 1.16; 95% CI: 0.83 to 1.63; p = 0.39) and the composite of death, myocardial infarction, and stroke (aHR: 1.14; 95% CI: 0.87 to 1.48; p = 0.35). Subgroup analysis of multivessel coronary disease, high SYNTAX score (>32), and diabetes showed consistent findings. CONCLUSIONS For the treatment of left main or multivessel coronary artery disease, PCI resulting in CR was associated with a similar long-term survival rate to CABG resulting in CR. Therefore, the ability to achieve CR should enter into the decision algorithm for choice of revascularization strategy.(C) 2017 Published by Elsevier on behalf of the American College of Cardiology Foundation

A 70‐year‐old man was admitted to our hospital with an abnormal chest X‐ray shadow. Bronchoscopy revealed an adenocarcinoma tumour with an epidermal growth factor receptor (EGFR) exon 19 deletion. Positron emission tomography–computed tomography scanning and magnetic resonance imaging showed advanced stage IV lung cancer. He was treated with erlotinib as a first‐line drug, which maintained a clinical response for 16 months. After disease progression, a re‐biopsy was done from the tumour in the right lower lobe. The obtained specimen harboured both small‐cell lung cancer (SCLC) transformation with retention of the EGFR 19 deletion and the development of an EGFR T790M mutation. We came across a very rare condition of concomitant T790M mutation and SCLC transformation after acquired resistance to EGFR‐tyrosine kinase inhibitor.

OBJECTIVES The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD). BACKGROUND The relative efficacy and safety of CABG versus PCI with DES for left main or multivessel CAD remain controversial. METHODS Data were pooled from the BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trials. The primary outcome was a composite of all-cause death, myocardial infarction, or stroke. RESULTS The median follow-up was 60 months, and follow-up was completed for 96.2% of patients. The rate of primary outcome was significantly lower with CABG than with PCI (13.0% vs. 16.0%; hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.69 to 1.00; p = 0.046). The difference was mainly driven by reduction in myocardial infarction (HR: 0.46; 95% CI: 0.33 to 0.64; p

BackgroundIn a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.ObjectivesThis study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis.MethodsWe randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis.ResultsAt 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012).ConclusionsDuring 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968)

Current guidelines recommend that coronary artery calcium (CAC) screening should only be used for intermediate risk groups (Framingham risk score [FRS] of 10%–20%). The CAC distributions and coronary artery disease (CAD) prevalence in various FRS strata were determined. The benefit to lower risk populations of CAC score-based screening was also assessed. In total, 1,854 participants (aged 40–79 years) without history of CAD, stroke, or diabetes were enrolled. CAC scores of > 0, ≥ 100, and ≥ 300 were present in 33.8%, 8.2%, and 2.9% of the participants, respectively. The CAC scores rose significantly as the FRS grew more severe (P < 0.01). The total CAD prevalence was 6.1%. The occult CAD prevalence in the FRS ≤ 5%, 6%–10%, 11%–20%, and > 20% strata were 3.4%, 6.7%, 9.0%, and 11.6% (P < 0.001). In multivariate logistic regression analysis adjusting, not only the intermediate and high risk groups but also the low risk (FRS 6%–10%) group had significantly increased odds ratio for occult CAD compared to the very low-risk (FRS ≤ 5%) group (1.89 [95% confidence interval, CI, 1.09–3.29] in FRS 6%–10%; 2.48 [95% CI, 1.47–4.20] in FRS 11%–20%; and 3.10 [95% CI, 1.75–5.47] in FRS > 20%; P < 0.05). In conclusion, the yield of screening for significant CAC and occult CAD is low in the very low risk population but it rises in low and intermediate risk populations., Graphical Abstract

ObjectivesWe compared 4-year efficacy and safety of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM).BackgroundFour-year comparison of SES with PES in diabetic patients has not been evaluated in a randomized manner.MethodsThis prospective, multicenter, randomized study compared SES (n = 200) and PES (n = 200) implantation in diabetic patients. We evaluated 4-year major adverse cardiac events (MACE) including death, myocardial infarction (MI), and target lesion revascularization (TLR).ResultsThe 2 groups had similar baseline characteristics. At 2 years, TLR (3.5% vs. 11.0%, log-rank, p < 0.01) and MACE (3.5% vs. 12.5%, log-rank, p < 0.01) were significantly lower in SES versus PES group with no difference of death or MI. At 4 years there were no differences in death (3.0% vs. 5.0%, p = 0.45) or MI (1.5% vs. 1.0%, p = 0.99) between SES and PES group. The TLR (7.5% vs. 12.0%, log-rank, p = 0.10) and MACE (11.0% vs. 16.0%, log-rank, p = 0.10) were statistically not different between SES and PES group. At multivariate Cox regression, post-procedural minimal lumen diameter (hazard ratio [HR]: 0.44, 95% confidence interval [CI]: 0.24 to 0.81, p < 0.01), hypercholesterolemia (HR: 2.21, 95% CI: 1.29 to 3.79, p < 0.01), and use of intravascular ultrasound (HR: 0.51, 95% CI: 0.26 to 0.99, p = 0.049) were independent predictors of 4-year MACE.ConclusionsSuperiority of SES over PES during 2 years was attenuated between 2 years and 4 years in diabetic patients. Use of intravascular ultrasound and larger post-procedural minimal lumen diameter were independent predictors of the improved long-term clinical outcomes.

ObjectivesWe performed the long-term follow-up of a large cohort of patients in a multicenter study receiving left main coronary artery (LMCA) revascularization.BackgroundLimited information is available on long-term outcomes for patients with unprotected LMCA disease who underwent coronary stent procedure or coronary artery bypass grafting (CABG).MethodsWe evaluated 2,240 patients with unprotected LMCA disease who received coronary stents (n = 1,102; 318 with bare-metal stents and 784 with drug-eluting stents) or underwent CABG (n = 1,138) between 2000 and 2006 and for whom complete follow-up data were available for at least 3 to 9 years (median 5.2 years). The 5-year adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction [MI], or stroke; and target vessel revascularization [TVR]) were compared with the use of the inverse probability of treatment weighted method and propensity-score matching.ResultsAfter adjustment for differences in baseline risk factors with the inverse probability of treatment weighting, the 5-year risk of death (hazard ratio [HR]: 1.13; 95% confidence interval [CI]: 0.88 to 1.44, p = 0.35) and the combined risk of death, Q-wave MI, or stroke (HR: 1.07; 95% CI: 0.84 to 1.37, p = 0.59) were not significantly different for patients undergoing stenting versus CABG. The risk of TVR was significantly higher in the stenting group than in the CABG group (HR: 5.11; 95% CI: 3.52 to 7.42, p < 0.001). Similar results were obtained in comparisons of bare-metal stent with concurrent CABG and of drug-eluting stent with concurrent CABG. In further analysis with propensity-score matching, overall findings were consistent.ConclusionsDuring 5-year follow-up, stenting showed similar rates of mortality and of the composite of death, Q-wave MI, or stroke but higher rates of TVR as compared with CABG for patients with unprotected LMCA disease.

ObjectivesThis study sought to evaluate the ability of minimal luminal area (MLA) measured by intravascular ultrasound (IVUS) to assess the functional significance of coronary artery disease.BackgroundThe use of IVUS to determine the functional significance of coronary artery lesions remains a matter for debate.MethodsFrom our prospective IVUS imaging database, between July 2009 and April 2010, 170 coronary lesions in 150 patients who underwent stress myocardial single-photon emission computed tomography (SPECT) performed within 1 month of IVUS evaluation were identified and analyzed. MLA and other parameters were measured by IVUS and compared with the results of myocardial SPECT.ResultsOverall, 45 lesions had positive SPECT, and 125 lesions had negative SPECT. The MLA of lesions with positive SPECT was smaller than the MLA of those with negative SPECT (1.7 ± 0.5 mm2 vs. 2.3 ± 1.1 mm2, p < 0.001). By logistic regression analysis, MLA (odds ratio: 3.1 by decrease of 1 mm2, 95% confidence interval [CI]: 1.75 to 5.5, p < 0.01) was an independent predictor of the positive SPECT. Using receiver-operator characteristic curve analysis, the best cutoff value of MLA was ≤2.1 mm2 with an 86.7% sensitivity, a 50.4% specificity, a 38.6% positive predictive value, and a 91.3% negative predictive value versus lesions with a positive SPECT (area under the curve: 0.690, 95% CI: 0.615 to 0.759, p < 0.01).ConclusionsThe best cutoff value of MLA measured by IVUS to predict myocardial ischemia was 2.1 mm2. The IVUS-measured MLA appeared to play a limited role in detecting functionally significant lesions assessed by myocardial SPECT.

ObjectivesThis study was designed to compare the clinical and angiographic outcomes of sirolimus-eluting stent (SES) and bare metal stent (BMS) implantation for unprotected left main coronary artery (LMCA) stenosis.BackgroundThe safety and effectiveness of SES implantation for unprotected LMCA stenosis have not been ascertained.MethodsElective SES implantation for de novo unprotected LMCA stenosis was performed in 102 consecutive patients with preserved left ventricular function from March 2003 to March 2004. Data from this group were compared to those from 121 patients treated with BMS during the preceding two years.ResultsCompared to the BMS group, the SES group received more direct stenting, had fewer debulking atherectomies, had a greater number of stents, had more segments stented, and underwent more bifurcation stenting. The procedural success rate was 100% for both groups. There were no incidents of death, stent thrombosis, Q-wave myocardial infarction (MI), or emergent bypass surgery during hospitalization in either group. Despite less acute gain (2.06 ± 0.56 mm vs. 2.73 ± 0.73 mm, p < 0.001) in the SES group, SES patients showed a lower late lumen loss (0.05 ± 0.57 mm vs. 1.27 ± 0.90 mm, p < 0.001) and a lower six-month angiographic restenosis rate (7.0% vs. 30.3%, p < 0.001) versus the BMS group. At 12 months, the rate of freedom from death, MI, and target lesion revascularization was 98.0 ± 1.4% in the SES group and 81.4 ± 3.7% in the BMS group (p = 0.0003).ConclusionsSirolimus-eluting stent implantation for unprotected LMCA stenosis appears safe with regard to acute and midterm complications and is more effective in preventing restenosis compared to BMS implantation.

ObjectivesWe performed the long-term (5-year) follow-up of a large cohort of patients who underwent drug-eluting stent (DES) or coronary artery bypass graft (CABG) surgery for multivessel revascularization.BackgroundLimited information is available on very long-term outcomes after multivessel DES treatment relative to CABG.MethodsWe evaluated 3,042 patients with multivessel disease who received DES (n = 1,547) or underwent CABG (n = 1,495) between January 2003 and December 2005, and for whom complete follow-up data were available for a median 5.6 years (interquartile range: 4.6 to 6.3 years). We compared adverse outcomes (death; a composite outcome of death, myocardial infarction, or stroke; and repeat revascularization).ResultsAfter adjustment for differences in baseline risk factors, 5-year risk of death (hazard ratio [HR]: 1.00; 95% confidence interval [CI]: 0.76 to 1.32, p = 0.99) and the combined risk of death, myocardial infarction, or stroke (HR: 0.97; 95% CI: 0.76 to 1.24, p = 0.81) were similar between the DES group and the CABG group. However, the rates of revascularization were significantly higher in the DES group (HR: 2.93; 95% CI: 2.20 to 3.90, p < 0.001). Similar results were obtained in comparisons of DES with CABG for high-risk clinical and anatomic subgroups with diabetes mellitus, abnormal ventricular function, age 65 years or more, and 3-vessel and left main disease. However, mortality benefit with DES implantation relative to CABG was noted in patients with 2-vessel disease (HR: 0.57; 95% CI: 0.36 to 0.92, p = 0.02).ConclusionsFor patients with multivessel disease, DES treatment, compared with CABG, showed similar rates of mortality and of the composite safety outcomes, but higher rates of revascularization up to 5 years.

ObjectivesWe undertook a meta-analysis to assess outcomes for drug-eluting stents (DES) and bare-metal stents (BMS) in percutaneous coronary intervention for unprotected left main coronary artery (ULMCA) stenosis.BackgroundUncertainty exists regarding the relative performance of DES versus BMS in percutaneous coronary intervention for unprotected left main coronary stenosis.MethodsOf a total of 838 studies, 44 met inclusion criteria (n = 10,342). The co-primary end points were mortality, myocardial infarction (MI), target vessel/lesion revascularization (TVR/TLR), and major adverse cardiac events (MACE: mortality, MI, TVR/TLR).ResultsEvent rates for DES and BMS were calculated at 6 to 12 months, at 2 years, and at 3 years. Crude event rates at 3 years were mortality (8.8% and 12.7%), MI (4.0% and 3.4%), TVR/TLR (8.0% and 16.4%), and MACE (21.4% and 31.6%). Nine studies were included in a comparative analysis (n = 5,081). At 6 to 12 months the adjusted odds ratio (OR) for DES versus BMS were: mortality 0.94 (95% confidence interval [CI]: 0.06 to 15.48; p = 0.97), MI 0.64 (95% CI: 0.19 to 2.17; p = 0.47), TVR/TLR 0.10 (95% CI: 0.01 to 0.84; p = 0.01), and MACE 0.34 (95% CI: 0.15 to 0.78; p = 0.01). At 2 years, the OR for DES versus BMS were: mortality 0.42 (95% CI: 0.28 to 0.62; p < 0.01), MI 0.16 (95% CI: 0.01 to 3.53; p = 0.13), and MACE 0.31 (95% CI: 0.15 to 0.66; p < 0.01). At 3 years, the OR for DES versus BMS were: mortality 0.70 (95% CI: 0.53 to 0.92; p = 0.01), MI 0.49 (95% CI: 0.26 to 0.92; p = 0.03), TVR/TLR 0.46 (95% CI: 0.30 to 0.69; p < 0.01), and MACE 0.78 (95% CI: 0.57 to 1.07; p = 0.12).ConclusionsOur meta-analysis suggests that DES is associated with favorable outcomes for mortality, MI, TVR/TLR, and MACE as compared to BMS in percutaneous coronary intervention for unprotected left main coronary artery stenosis.

ObjectivesThe purpose of this study was to evaluate the risk of stent thrombosis (ST), clinical outcomes, and the benefits of extended clopidogrel use after drug-eluting stent (DES) implantation.BackgroundData are limited regarding uniform evaluation of ST and the influence of clopidogrel continuation beyond 12 months on late events after DES treatment.MethodsWe identified 7,221 patients who received DES implantation (n = 3,160) or bare-metal stent (BMS) implantation (n = 4,061), and compared long-term adverse outcomes. Additionally, 2,851 patients with DES surviving 12 months without major events were analyzed according to clopidogrel continuation.ResultsThe adjusted-risk of overall ST was similar in the 2 groups. After 1 year, however, DES patients showed a higher risk of ST; definite/probable (hazard ratio [HR]: 3.55, 95% confidence interval [CI]: 1.26 to 9.99). The adjusted-risk of death (HR: 0.60, 95% CI: 0.46 to 0.79), death/myocardial infarction (HR: 0.63, 95% CI: 0.49 to 0.81), and target lesion revascularization (HR: 0.32, 95% CI: 0.24 to 0.43) were significantly lower in the DES group than in the BMS group. Continuing clopidogrel beyond 12 months was not associated with a reduced risk for ST (HR: 0.54, 95% CI: 0.07 to 4.23), death (HR: 1.20, 95% CI: 0.55 to 2.66), or death/myocardial infarction (HR: 1.16, 95% CI: 0.56 to 2.42) after DES implantation.ConclusionsAs compared with BMS, DES showed a similar risk of overall ST, but a higher risk of very late ST. The rates of death, death/myocardial infarction, and target lesion revasuclarization were significantly lower in the DES group. Clopidogrel continuation beyond 1 year did not appear to reduce ST and clinical events after DES implantation.

ObjectivesThis study sought to evaluate the long-term safety and effectiveness of percutaneous coronary intervention (PCI), as compared with coronary artery bypass grafting (CABG), for unprotected left main coronary artery (LMCA) disease.BackgroundData on the long-term (beyond 5-year) comparative results of treatment of unprotected LMCA disease with stent implantation or CABG are limited.MethodsWe performed a 10-year clinical follow-up of 350 patients with unprotected LMCA disease who underwent PCI with bare-metal stents (BMS) (n = 100) or CABG (n = 250) from January 1995 to April 1999, and 5-year clinical follow-up of 395 patients with unprotected LMCA disease who underwent PCI with drug-eluting stents (DES) (n = 176) or CABG (n = 219) from January 2003 to May 2004. The primary safety end points were all-cause mortality and the composite of death, Q-wave myocardial infarction (MI), or stroke, and the primary efficacy end point was target vessel revascularization (TVR).ResultsIn the 10-year follow-up cohort of BMS and concurrent CABG, the adjusted risks of death (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.44 to 1.50; p = 0.50) and the composite of death, Q-wave MI, or stroke (HR: 0.92; 95% CI: 0.55 to 1.53; p = 0.74) were similar between the 2 groups. The rate of TVR was significantly higher in the group that received BMS (HR: 10.34; 95% CI: 4.61 to 23.18; p < 0.001). In the 5-year follow-up cohort of DES and concurrent CABG, there was no significant difference in the adjusted risk of death (HR: 0.83; 95% CI: 0.34 to 2.07; p = 0.70) or the risk of the composite outcome (HR: 0.91; 95% CI: 0.45 to 1.83; p = 0.79). The rates of TVR were also higher in the DES group than the CABG group (HR: 6.22; 95% CI: 2.26 to 17.14; p < 0.001).ConclusionsFor the treatment of unprotected LMCA disease, PCI with stent implantation showed similar long-term mortality and rates of death, Q-wave MI, or stroke. However, stenting, even with DES, was associated with higher rates of repeat revascularization than was CABG.

ObjectivesWe sought to evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM).BackgroundAlthough cilostazol has reduced the extent of neointimal hyperplasia and restenosis in patients after bare-metal stent implantation, it is not known whether this effect occurs after DES implantation in diabetic patients.MethodsThis randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol, triple group, n = 200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n = 200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6 months.ResultsThe 2 groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25 ± 0.53 mm vs. 0.38 ± 0.54 mm, p = 0.025) and in-segment (0.42 ± 0.50 mm vs. 0.53 ± 0.49 mm, p = 0.031) late loss were significantly lower in the triple versus standard group, as were 6-month in-segment restenosis (8.0% vs. 15.6%, p = 0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p = 0.034). At 9 months, major adverse cardiac events, including death, myocardial infarction, and TLR, tended to be lower in the triple than in the standard group (3.0% vs. 7.0%, p = 0.066). Multivariate analysis showed that sirolimus-eluting stents and the use of cilostazol were strong predictors of reduced restenosis or TLR.ConclusionsTriple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients.

ObjectivesThe aim of this study was to assess the clinical and morphological predictors for functionally significant in-stent restenosis (ISR).BackgroundAlthough they have been studied de novo in native coronary artery lesions, the relationships between clinical and morphological characteristics and the hemodynamic significance of ISR are not well understood.MethodsIn 175 patients with ISR of a single coronary artery (angiographic stenosis >50%), we compared quantitative coronary angiography and intravascular ultrasound (IVUS) with stress myocardial single-photon emission computed tomography (SPECT). A positive SPECT was a reversible perfusion defect in the territory of the ISR artery.ResultsOverall, 103 (59%) patients had a positive SPECT. In-segment IVUS minimal lumen area (MLA) was significantly smaller in lesions with positive SPECT compared with negative SPECT (1.7 ± 0.5 mm2 vs. 2.4 ± 0.8 mm2, p < 0.001). Stent underexpansion (minimal stent area

ObjectivesThis study sought to evaluate the safety and efficacy of second-generation drug-eluting stents (DES) for patients with unprotected left main coronary artery (ULMCA) stenosis.BackgroundThe clinical benefit of second-generation DES for ULMCA stenosis has not been determined.MethodsThe authors assessed 334 consecutive patients who received everolimus-eluting stents (EES) for ULMCA stenosis between 2009 and 2010. The 18-month incidence rates of major adverse cardiac or cerebrovascular events (MACCE), including death, myocardial infarction (MI), stroke, or ischemia-driven target vessel revascularization (TVR), were compared with those of a randomized study comparing patients who received sirolimus-eluting stents (SES) (n = 327) or coronary artery bypass grafts (CABG) (n = 272).ResultsEES (8.9%) showed a comparable incidence of MACCE as SES (10.8%; adjusted hazard ratio [aHR] of EES: 0.84; 95% confidence interval [CI]: 0.51 to 1.40; p = 0.51) and CABG (6.7%, aHR of EES: 1.40; 95% CI: 0.78 to 2.54; p = 0.26). The composite incidence of death, MI, or stroke also did not differ among patients receiving EES (3.3%), SES (3.7%; aHR of EES: 0.63; 95% CI: 0.27 to 1.47; p = 0.29), and CABG (4.8%; aHR of EES: 0.67; 95% CI: 0.29 to 1.54; p = 0.34). However, the incidence of ischemia-driven TVR in the EES group (6.5%) was higher than in the CABG group (2.6%, aHR of EES: 2.77; 95% CI: 1.17 to 6.58; p = 0.02), but comparable to SES (8.2%, aHR of EES: 1.14; 95% CI: 0.64 to 2.06; p = 0.65). Angiographic restenosis rates were similar in the SES and EES groups (13.8% vs. 9.2%, p = 0.16).ConclusionsSecond-generation EES had a similar 18-month risk of MACCE for ULMCA stenosis as first-generation SES or CABG. (Evaluation of Outcomes of EES Implantation for Unprotected Left Main Coronary Artery Stenosis [PRECOMBAT-2]; NCT01348022)

ObjectivesThis study sought to investigate whether the outcome of drug-eluting stent (DES) treatment and that of coronary artery bypass grafting (CABG) differed in diabetic and nondiabetic patients with unprotected left main coronary artery (LMCA) disease.BackgroundDiabetes mellitus has been shown to be a risk factor for adverse events and a major determinant in selection of a revascularization strategy in patients with multivessel or LMCA disease.MethodsA total of 1,474 patients with unprotected LMCA stenosis who received DES (n = 784) or underwent CABG (n = 690) were examined. We compared the effects of these 2 treatments on long-term clinical outcomes (death; the composite of death, Q-wave myocardial infarction [MI], or stroke; and target vessel revascularization [TVR]), according to diabetic status.ResultsAfter adjustment of covariates, the risk of death (hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.62 to 1.46, p = 0.83) and the composite of death, Q-wave MI, or stroke (HR: 0.96, 95% CI: 0.65 to 1.42, p = 0.85) at 3 years were similar in the DES and CABG groups. However, the rate of TVR was significantly higher in the DES group (HR: 4.31, 95% CI: 2.28 to 8.15, p < 0.001). These trends were consistent in both diabetic and nondiabetic patients. We also did not observe a diabetes-associated excess risk of death (pinteraction = 0.90 and 0.16), or a composite of death, Q-wave MI, or stroke (pinteraction = 0.68 and 0.93), or TVR (pinteraction = 0.23 and 0.92), between patients receiving either treatment.ConclusionsThe prognostic impact of diabetes on long-term treatment with DES or CABG for patients with unprotected LMCA disease was minimal.

ObjectivesIn this substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, we investigated the relationship between chronic kidney disease (CKD) and clinical outcomes, and compared the safety and efficacy of bivalirudin monotherapy versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI).BackgroundCKD is an important predictor of prognosis in the general population. The outcomes of patients with CKD and acute coronary syndromes (ACS) have not been well studied.MethodsIn the ACUITY study, 13,819 patients with moderate- and high-risk ACS undergoing an early, invasive strategy were randomly assigned to 1 of 3 antithrombin regimens: a heparin plus a GPI, bivalirudin plus a GPI, or bivalirudin monotherapy. CKD (creatinine clearance

ObjectivesThe aim of this study was to evaluate long-term clinical outcomes after implantation of sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) among patients with unprotected left main coronary artery (LMCA) disease.BackgroundThere have been few comparisons of long-term outcomes among currently available drug-eluting stents (DES) for the treatment of LMCA disease.MethodsA total of 858 consecutive patients with unprotected LMCA stenosis were treated with SES (n = 669) or PES (n = 189) between May 2003 and June 2006. Primary outcome was the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR).ResultsBaseline clinical and angiographic characteristics were similar in the 2 groups. During 3 years of follow-up, the adjusted risk of primary composite outcome was similar among the groups (SES vs. PES: 25.8% vs. 25.7%, hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.64 to 1.41, p = 0.79). The 2 groups also showed a comparable adjusted rate of each component of outcome: death (9.1% vs. 11.0%, HR: 0.92, 95% CI: 0.47 to 1.80, p = 0.82), MI (8.1% vs. 8.0%, HR: 0.80, 95% CI: 0.43 to 1.48, p = 0.47), and TVR (12.1% vs. 10.6%, HR: 1.10, 95% CI: 0.53 to 2.29, p = 0.81). The 3-year rates of definite or probable stent thrombosis were 0.6% in the SES group and 1.6% in the PES group (adjusted p = 0.18).ConclusionsIn consecutive patients with unprotected LMCA disease undergoing DES implantation, SES and PES showed similar long-term clinical outcomes in terms of death, MI, repeat revascularization, and stent thrombosis.

ObjectivesWe evaluated the axial location of plaque ruptures in native coronary arteries.BackgroundIt is clinically important to understand the potential sites of plaque rupture.MethodsWe performed three-vessel intravascular ultrasound (IVUS) examination in 392 patients; 231 had acute coronary syndrome (ACS) and 161 had stable angina pectoris (SAP). The IVUS detected plaque ruptures in 206 patients: 158 ACS patients and 48 SAP patients. The distance between each coronary plaque rupture segment and the respective coronary ostium was measured with motorized IVUS transducer pullback in all three coronary arteries.ResultsThere were a total of 273 plaque ruptures in these 206 patients; 143 in the left anterior descending artery (LAD), 40 in the left circumflex artery (LCX), and 90 in the right coronary artery (RCA). There were 67 plaque ruptures in SAP patients and 206 in ACS patients; there were 197 culprit/target lesion plaque ruptures and 76 non-culprit/non-target lesion plaque ruptures. The LAD plaque ruptures were predominantly located between 10 and 40 mm from the LAD ostium (83%, 119 of 143). The LCX plaque ruptures were evenly distributed in the entire LCX tree. Most RCA plaque ruptures were located in segments between 10 and 40 mm (48%, 43 of 90) and in segments >70 mm from the ostium (32%, 29 of 90).ConclusionsThree-vessel IVUS imaging showed that plaque ruptures occurred mainly in proximal segments of the LAD (83% of LAD plaque rupture), the proximal and distal segments of the RCA (48% and 32% of RCA plaque ruptures, respectively), and the entire LCX.

ObjectivesThis randomized, prospective, double-blind, multicenter study compared nephrotoxicity of the nonionic iso-osmolar contrast media (CM) iodixanol versus the ionic low-osmolar CM ioxaglate in patients with chronic renal insufficiency undergoing coronary angiography.BackgroundThe properties of iodinated CM might contribute to the incidence of contrast-induced nephropathy (CIN).MethodsPatients with renal impairment undergoing coronary angiography were randomly assigned to iodixanol (n = 72) or ioxaglate (n = 74).ResultsBaseline characteristics were well-matched between the 2 groups. The predicted risk score for CIN was similar in the iodixanol and in the ioxaglate groups (11.9 ± 4.1 vs. 11.8 ± 4.1), as was the use of N-acetylcysteine (70% vs. 73%). The primary end point of the study, median peak increase of serum creatinine from day 0 through day 3 after angiography, did not differ between the iodixanol (0.09 mg/dl; interquartile range 0.00 to 0.30 mg/dl) and the ioxaglate (0.15 mg/dl; interquartile range 0.00 to 0.40 mg/dl; p = 0.07) groups. The percentages of patients with a peak increase of serum creatinine ≥0.5 mg/dl (15.9% in iodixanol vs. 18.2% in ioxaglate), ≥1.0 mg/dl (1.4% vs. 4.5%), and ≥25% or ≥0.5 mg/dl (15.9% vs. 24.2%, respectively) also did not differ significantly between the 2 groups.ConclusionsIn high-risk patients undergoing coronary angiographic procedures, use of the nonionic iso-osmolar CM iodixanol does not reduce renal deterioration in patients with renal impairment, compared with the ionic low-osmolar CM ioxaglate. Given that the study was underpowered to compare nephrotoxicity of the 2 groups under the active medical protection of CIN, a larger randomized study is warranted that will enroll patients with higher risks of CIN under a strict control of hydration regimens and adjunctive medications.

ObjectivesWe evaluated safety and efficacy of triple antiplatelet therapy with aspirin, clopidogrel, or ticlopidine and cilostazol after coronary stenting.BackgroundTriple antiplatelet therapy might have beneficial effect to prevent thrombotic complications in patients undergoing coronary stenting.MethodsPatients undergoing successful coronary stenting were divided into dual antiplatelet therapy (aspirin plus clopidogrel or ticlopidine, group I, n = 1,597) and triple antiplatelet therapy (aspirin plus clopidogrel or ticlopidine plus cilostazol, group II, n = 1,415) groups. The primary end point included death, myocardial infarction, target lesion revascularization, or stent thrombosis within 30 days. The secondary end point was side effects of study drugs, including major bleeding, vascular complication, hepatic dysfunction, and hematological complications.ResultsMulti-vessel stenting and the use of long stents were more prevalent in group II than in group I. The primary end point was 0.8% in group I and 0.3% in group II (p = 0.085). Stent thrombosis within 30 days was significantly lower in group II (n = 1, 0.1%) than in group I (n = 9, 0.5%; p = 0.024). The independent predictors of stent thrombosis were primary stenting (odds ratio [OR] 7.9, 95% confidence interval [CI] 2.0 to 30.8, p = 0.003) and triple therapy (OR 0.12, 95% CI 0.015 to 0.98, p = 0.048). The overall adverse drug effects, including major bleeding, neutropenia, and thrombocytopenia, were no different between two groups (1.8% vs. 2.6%, p = 0.104).ConclusionsCompared with the dual antiplatelet regimen, triple antiplatelet therapy seemed to be more effective in preventing thrombotic complications after stenting without an increased risk of side effects. Triple antiplatelet therapy might be safely applied in patients or lesions with a high risk of stent thrombosis.

Objectives The study sought to investigate the impact of different computing methods for composite endpoints other than time-to-event (TTE) statistics in a large, multicenter registry of unprotected left main coronary artery (ULMCA) disease. Background TTE statistics for composite outcome measures used in ULMCA studies consider only the first event, and all the contributory outcomes are handled as if of equal importance. Methods The TTE, Andersen-Gill, win ratio (WR), competing risk, and weighted composite endpoint (WCE) computing methods were applied to ULMCA patients revascularized by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) at 14 international centers. Results At a median follow-up of 1,295 days (interquartile range: 928 to 1,713 days), all analyses showed no difference in combinations of death, myocardial infarction, and cerebrovascular accident between PCI and CABG. When target vessel revascularization was incorporated in the composite endpoint, the TTE (p = 0.03), Andersen-Gill (p = 0.04), WR (p = 0.025), and competing risk (p < 0.001) computing methods showed CABG to be significantly superior to PCI in the analysis of 1,204 propensity-matched patients, whereas incorporating the clinical relevance of the component endpoints using WCE resulted in marked attenuation of the treatment effect of CABG, with loss of significance for the difference between revascularization strategies (p = 0.10). Conclusions In a large study of ULMCA revascularization, incorporating the clinical relevance of the individual outcomes resulted in sensibly different findings as compared with the conventional TTE approach. In particular, using the WCE computing method, PCI and CABG were no longer significantly different with respect to the composite of death, myocardial infarction, cerebrovascular accident, or target vessel revascularization at a median of 3 years.