Data-driven models for the prediction of coronary atherosclerotic plaque progression/regression.

Coronary artery disease is defined by the existence of atherosclerotic plaque on the arterial wall, which can cause blood flow impairment, or plaque rupture, and ultimately lead to myocardial ischemia. Intravascular ultrasound (IVUS) imaging can provide a detailed characterization of lumen and vessel features, and so plaque burden, in coronary vessels. Prediction of the regions in a vascular segment where plaque burden can either increase (progression) or decrease (regression) following a certain therapy, has remained an elusive major milestone in cardiology. Studies like IBIS-4 showed an association between plaque burden regression and high-intensity rosuvastatin therapy over 13 months. Nevertheless, it has not been possible to predict if a patient would respond in a favorable/adverse fashion to such a treatment. This work aims to (i) Develop a framework that processes lumen and vessel cross-sectional contours and extracts geometric descriptors from baseline and follow-up IVUS pullbacks; and to (ii) Develop, train, and validate a machine learning model based on baseline/follow-up IVUS datasets that predicts future percent of atheroma volume changes in coronary vascular segments using only baseline information, i.e. geometric features and clinical data. This is a post hoc analysis, revisiting the IBIS-4 study. We employed 140 arteries, from 81 patients, for which expert delineation of lumen and vessel contours were available at baseline and 13-month follow-up. Contour data from baseline and follow-up pullbacks were co-registered and then processed to extract several frame-wise features, e.g. areas, plaque burden, eccentricity, etc. Each pullback was divided into regions of interest (ROIs), following different criteria. Frame-wise features were condensed into region-wise markers using tools from statistics, signal processing, and information theory. Finally, a stratified 5-fold cross-validation strategy (20 repetitions) was used to train/validate an XGBoost regression models. A feature selection method before the model training was also applied. When the models were trained/validated on ROI defined by the difference between follow-up and baseline plaque burden, the average accuracy and Mathews correlation coefficient were 0.70 and 0.41 respectively. Using a ROI partition criterion based only on the baseline's plaque burden resulted in averages of 0.60 accuracy and 0.23 Mathews correlation coefficient. An XGBoost model was capable of predicting plaque progression/regression changes in coronary vascular segments of patients treated with rosuvastatin therapy in 13 months. The proposed method, first of its kind, successfully managed to address the problem of stratification of patients at risk of coronary plaque progression, using IVUS images and standard patient clinical data.

Drug-Eluting or Bare-Metal Stents for Left Anterior Descending or Left Main Coronary Artery Revascularization

BACKGROUND: New-generation drug-eluting stents (DES) reduce target-vessel revascularization compared with bare-metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no-LAD/LM]). METHODS AND RESULTS: The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1-stage individual patient data meta-analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no-LAD/LM group. At 6-year follow-up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (P interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68­0.85) than in the no-LAD/LM territories (HR, 0.93; 95% CI, 0.83­1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70­0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65­0.85) in patients with LAD/LM disease randomized to DES. An interaction (P=0.004) was also found for all-cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76­0.97). CONCLUSIONS: As compared with BMS, new-generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses.

Drug-eluting or bare-metal stents for percutaneous coronary intervention: a systematic review and individual patient data meta-analysis of randomised clinical trials

Background New-generation drug-eluting stents (DES) have mostly been investigated in head-to-head non-inferiority trials against early-generation DES and have typically shown similar efficacy and superior safety. How the safety profile of new-generation DES compares with that of bare-metal stents (BMS) is less clear.Methods We did an individual patient data meta-analysis of randomized clinical trials to compare outcomes after implantation of new-generation DES or BMS among patients undergoing percutaneous coronary intervention. The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random-effects meta-analysis and examined at maximum follow-up and a 1-year landmark. Risk estimates are reported as hazard ratios (HRs) with 95% CIs. This study is registered in PROSPERO, number CRD42017060520.Findings We obtained individual data for 26 616 patients in 20 randomized trials. Mean follow-up was 3·2 (SD 1·8) years. The risk of the primary outcome was reduced in DES recipients compared with BMS recipients (HR 0·84, 95% CI 0·78­0·90, p<0·001) owing to a reduced risk of myocardial infarction (0·79, 0·71­0·88, p<0·001) and a possible slight but non-significant cardiac mortality benefit (0·89, 0·78­1·01, p=0·075). All-cause death was unaffected (HR with DES 0·96, 95% CI 0·88­1·05, p=0·358), but risk was lowered for definite stent thrombosis (0·63, 0·50­0·80, p<0·001) and target-vessel revascularization (0·55, 0·50­0·60, p<0·001). We saw a time-dependent treatment effect, with DES being associated with lower risk of the primary outcome than BMS up to 1 year after placement. While the effect was maintained in the longer term, there was no further divergence from BMS after 1 year. Interpretation The performance of new-generation DES in the first year after implantation means that BMS should no longer be considered the gold standard for safety. Further development of DES technology should target improvements in clinical outcomes beyond 1 year. (AU)

Dual antiplatelet therapy duration based on ischemic and bleeding risks after coronary stenting

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials

Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods: A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk...

Validity of SYNTAX score II for risk stratification of percutaneous coronary interventions: A patient-level pooled analysis of 5,433 patients enrolled in contemporary coronary stent trials.

OBJECTIVES: To assess the clinical profile and long-term mortality in SYNTAX score II based strata of patients who received percutaneous coronary interventions (PCI) in contemporary randomized trials. BACKGROUND: The SYNTAX score II was developed in the randomized, all-comers' SYNTAX trial population and is composed by 2 anatomical and 6 clinical variables. The interaction of these variables with the treatment provides individual long-term mortality predictions if a patient undergoes coronary artery bypass grafting (CABG) or PCI. METHODS: Patient-level (n=5433) data from 7 contemporary coronary drug-eluting stent (DES) trials were pooled. The mortality for CABG or PCI was estimated for every patient. The difference in mortality estimates for these two revascularization strategies was used to divide the patients into three groups of theoretical treatment recommendations: PCI, CABG or PCI/CABG (the latter means equipoise between CABG and PCI for long term mortality). RESULTS: The three groups had marked differences in their baseline characteristics. According to the predicted risk differences, 5115 patients could be treated either by PCI or CABG, 271 should be treated only by PCI and, rarely, CABG (n=47) was recommended. At 3-year follow-up, according to the SYNTAX score II recommendations, patients recommended for CABG had higher mortality compared to the PCI and PCI/CABG groups (17.4%; 6.1% and 5.3%, respectively; P<0.01). CONCLUSIONS: The SYNTAX score II demonstrated capability to help in stratifying PCI procedures.