Effect of rosuvastatin 20 mg versus rosuvastatin 5 mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial.

BACKGROUND: Current guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients. TRIAL DESIGN: This investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months. CONCLUSIONS: The SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.

Machine Learning-Based prediction of Post-Treatment ambulatory blood pressure in patients with hypertension.

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.

Primary versus rescue retrograde approach for chronic total coronary occlusion.

OBJECTIVES: We aimed to assess the advantages of using the retrograde approach as an initial strategy rather than as a rescue strategy for complex chronic total occlusions (CTOs). BACKGROUND: Even for complex CTOs where a retrograde approach is deemed necessary, an antegrade approach is frequently used as an initial strategy in real-world practice. METHODS: We evaluated 352 retrograde procedures for CTO conducted at our high-volume center between January 2007 and January 2019. Procedural efficiency and safety was assessed based on the guidewire manipulation time (GWMT) and the occurrence of procedure-related adverse events for the primary retrograde approach (PRA) and the rescue retrograde approach (RRA). RESULTS: PRA and RRA were used in 191 (54.3%) and 161 (45.7%) of the CTO procedures, respectively. The complexity of the CTO lesion was significantly higher in the PRA group than in the RRA group (Japanese-CTO score, 2.62 ± 1.07 vs. 2.38 ± 1.06, p = 0.037). The technical success rate of two groups was similar (p = 0.47). The median GWMT required for PRA was significantly shorter than that for RRA (85 [interquartile range, 55-126] vs. 120 [85-157] min, p < 0.001). The total duration of the procedure and fluoroscopic time were shorter, and the number of guidewires and amount of contrast used during the index procedure were smaller in the PRA group. The incidence of procedure-related adverse events was not significantly different between the two groups. CONCLUSIONS: PRA showed higher procedural efficiency than RRA with comparable safety. Opting for PRA for complex CTOs might be a rational decision to enhance the procedural efficiency.

Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion.

BACKGROUND: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials. METHODS: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator. The primary end point was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life was assessed at baseline and at 1, 6, 12, 24, and 36 months. Because of slow recruitment, the trial was stopped before completion of the 1284 planned enrollments. RESULTS: Between March 2010 and September 2016, 834 patients were randomly assigned to the CTO-PCI (n=417) or no CTO-PCI (n=398) strategy. Among the patients assigned to the no CTO-PCI strategy, 78 (19.6%) crossed over to receive staged CTO-PCI within 3 days of randomization. The overall CTO-PCI success rate was 90.6%. Serious nonfatal complications associated with CTO-PCI occurred in 3 patients (1 stroke, 1 cardiac tamponade, and 1 patient with recurrent episodes of ventricular tachyarrhythmia induced by intracoronary thrombus). Approximately half of the patients in each group underwent PCI for an average of 1.3 non-CTO lesions, resulting in a comparable residual SYNTAX score (Synergy Between PCI With TAXUS and Cardiac Surgery; 3.7±5.4 versus 4.0±5.9, P=0.42) confined to non-CTO vessels. During a median follow-up of 4.0 years (interquartile range, 2.4 to 5.1 years), there was no significant difference between the CTO-PCI and the no CTO-PCI strategies in the incidence of the primary end point (22.3% versus 22.4%, hazard ratio, 1.03; 95% CI, 0.77 to 1.37; P=0.86). Both CTO-PCI and no CTO-PCI strategy were associated with significant improvements but without between-group differences in disease-specific health status that was sustained through 36 months. CONCLUSIONS: CTO-PCI was feasible with high success rates. There was no difference in the incidence of major adverse cardiovascular events with CTO-PCI versus no CTO-PCI, but the study was limited by low power for clinical end points and high crossover rates between groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01078051.

Clinical outcomes of contemporary drug-eluting stents in patients with and without diabetes mellitus: Multigroup propensity-score analysis using data from stent-specific, multicenter, prospective registries.

BACKGROUND: Whether the diabetic status differentially affects the clinical outcomes with different drug-eluting stents (DES) has been controversial. METHODS AND RESULTS: From stent-specific, prospective DES registries, we evaluated 17,184 patients (11,428 in non-diabetics and 5,756 in diabetics) who received several contemporary DES: 3570 sirolimus-eluting stents (SES), 5,023 cobalt-chromium everolimus-eluting stents (CoCr-EES), 2,985 platinum-chromium EES (PtCr-EES), 2,913 Resolute zotarolimus-eluting stents (Re-ZES), and 2,693 biodegradable-polymer biolimus-eluting stents (BP-BES). The primary outcome was patient-oriented composite endpoint (POCE, a composite of all-cause death, any myocardial infarction, and any revascularization) at 3-year follow-up and target-vessel failure (a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization) at 3 years was also evaluated. In non-diabetics, the rates of POCE were not significantly different (CoCr-EES 14.3%, PtCr-EES 13.0%, Re-ZES 14.3%, BP-BES 13.4%, and SES 14.6%; overall p = .39). In diabetics, similar results were revealed (CoCr-EES 18.4%, PtCr-EES 20.3%, Re-ZES 17.3%, BP-BES 17.7%, and SES 17.8%; overall p = .44). In multiple treatment propensity-score weighting analysis, regardless of the diabetic status, the hazard ratios for POCE between-individual comparison were similar. Target-vessel failure (a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization) was also comparable except the higher ratio of Re-ZES than PtCr-EES (hazard ratio 1.25, 1.26, 95% confidence interval 1.00-1.55, p = .048) in patients without diabetes. CONCLUSIONS: In this clinical-practice registry study, regardless the diabetic status, the 3-year rates of the primary outcome were similar among different types of DES, suggesting no differential clinical response between contemporary DES in patients with or without diabetes.

Verifying Death Reports in the Platelet Inhibition and Patient Outcomes (PLATO) Trial.

BACKGROUND: Excess vascular deaths in the PLATO trial comparing ticagrelor to clopidogrel have been repeatedly challenged by the Food and Drug Administration (FDA) reviewers and academia. Based on the Freedom of Information Act, BuzzFeed won a court order and shared with us the complete list of reported deaths for the ticagrelor FDA New Drug Application (NDA) 22-433. This dataset was matched against local patient-level records from PLATO sites monitored by the sponsor. STUDY QUESTION: Whether FDA death data in the PLATO trial matched the local site records. STUDY DESIGN: The NDA spreadsheet contains 938 precisely detailed PLATO deaths. We obtained and validated local evidence for 52 deaths among 861 PLATO patients from 14 enrolling sites in 8 countries and matched those with the official NDA dataset submitted to the FDA. MEASURES AND OUTCOMES: Existence, precise time, and primary cause of deaths in PLATO. RESULTS: Discrepant to the NDA document, sites confirmed 2 extra unreported deaths (Poland and Korea) and failed to confirm 4 deaths (Malaysia). Of the remaining 46 deaths, dates were reported correctly for 42 patients, earlier (2 clopidogrel), or later (2 ticagrelor) than the actual occurrence of death. In 12 clopidogrel patients, cause of death was changed to "vascular," whereas 6 NDA ticagrelor "nonvascular" or "unknown" deaths were site-reported as of "vascular" origin. Sudden death was incorrectly reported in 4 clopidogrel patients, but omitted in 4 ticagrelor patients directly affecting the primary efficacy PLATO endpoint. CONCLUSIONS: Many deaths were inaccurately reported in PLATO favoring ticagrelor. The full extent of mortality misreporting is currently unclear, while especially worrisome is a mismatch in identifying primary death cause. Because all PLATO events are kept in the cloud electronic Medidata Rave capture system, securing the database content, examining the dataset changes or/and repeated entries, identifying potential interference origin, and assessing full magnitude of the problem are warranted.

Effects of ezetimibe/simvastatin 10/10 mg versus Rosuvastatin 10 mg on carotid atherosclerotic plaque inflammation.

BACKGROUND: Using 18F-fluorodeoxyglucose (18FDG) positron emission tomography-computed tomography (PET/CT) imaging, we examined the effects of ezetimibe/simvastatin 10/10 mg versus rosuvastatin 10 mg on carotid atherosclerotic plaque inflammation. Whether the combination therapy of ezetimibe with low-dose statin is as effective as potent statin monotherapy in attenuating carotid atherosclerotic plaque inflammation remains unclear. METHODS: In this 2-by-2 factorial trial, 50 patients with 18FDG uptake (target-to-background ratio [TBR] ≥1.6) in the carotid artery and acute coronary syndrome were randomized to receive either simvastatin/ezetimibe 10/10 mg or rosuvastatin 10 mg. 18FDG PET/CT examinations were performed at baseline and at 6 months. The percent change in the TBR of the index vessel at the most diseased segment (MDS) was the primary endpoint. RESULTS: Baseline characteristics of the two groups were largely similar. At 6-month follow-up, the MDS TBR of the index vessel and aorta significantly decreased in ezetimibe/simvastatin group and tended to decrease in rosuvastatin group. However, the percent change in the MDS TBR of the index vessel was similar between the 2 groups (- 10.22 ± 17.49% vs. -5.84 ± 15.78%, respectively, p = 0.357), as was the percent change in the whole vessel TBR of the index vessel. Likewise, the changes in the MDS TBR or whole vessel TBR of the aorta were similar in both groups. Total cholesterol and low-density lipoprotein cholesterol levels improved to a similar degree in both groups. CONCLUSION: Treatment with ezetimibe/simvastatin versus rosuvastatin resulted in a similar improvement of carotid atherosclerotic plaque inflammation, suggesting their equivalent anti-inflammatory effects. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov : NCT02378064, 3-4-2015. /IRB No. 2015-0194.

Deferred vs. performed revascularization for coronary stenosis with grey-zone fractional flow reserve values: data from the IRIS-FFR registry.

Aims: The optimal fractional flow reserve (FFR) cut-off value for revascularization is debated. We evaluated the prognosis for deferred and performed revascularization in coronary stenosis with FFR values in the grey zone (0.75-0.80). Methods and results: This study included 1334 native coronary stenosis with grey-zone FFR values in 1334 patients from the prospective multicentre Interventional Cardiology Research In-cooperation Society Fractional Flow Reserve registry. Revascularization was deferred for 683 patients (deferred group) and performed for 651 (performed group). The primary outcome, a composite of death, target-vessel myocardial infarction (MI), and target vessel revascularization (TVR) occurred in 55 (8.1%) patients in the deferred group and 55 (8.4%) in the performed group [adjusted hazard ratio (aHR) 1.05, 95% confidence interval (CI) 0.67-1.66; P = 0.79] during a median follow-up of 2.9 years (interquartile range 1.5-4.1 years). Overall mortality and spontaneous MI did not differ between the groups (mortality 2.5% vs. 2.0%; aHR 0.82, 95% CI 0.34-2.00; P = 0.66; spontaneous MI 0.7% vs. 0.5%; aHR 1.85, 95% CI 0.35-9.75; P = 0.47). Myocardial infarction was significantly higher in the performed group (0.7% vs. 3.2%; aHR 0.27, 95% CI 0.09-0.80; P = 0.02) mainly because of a higher risk of periprocedural MI. Target vessel revascularization was significantly higher in the deferred group (5.7% vs. 3.7%; aHR 2.17, 95% CI 1.17-4.02; P = 0.01). Conclusion: For coronary stenosis with grey-zone FFR, revascularization was not associated with better clinical outcomes. The higher likelihood of periprocedural MI with revascularization was offset by the higher likelihood of TVR with deferral. Trial registration: Clinicaltrials.gov identifier: NCT01366404.

Fractional Flow Reserve and Cardiac Events in Coronary Artery Disease: Data From a Prospective IRIS-FFR Registry (Interventional Cardiology Research Incooperation Society Fractional Flow Reserve).

BACKGROUND: We evaluated the prognosis of deferred and revascularized coronary stenoses after fractional flow reserve (FFR) measurement to assess its revascularization threshold in clinical practice. METHODS: The IRIS-FFR registry (Interventional Cardiology Research In-cooperation Society Fractional Flow Reserve) prospectively enrolled 5846 patients with ≥1coronary lesion with FFR measurement. Revascularization was deferred in 6468 lesions and performed in 2165 lesions after FFR assessment. The primary end point was major adverse cardiac events (cardiac death, myocardial infarction, and repeat revascularization) at a median follow-up of 1.9 years and analyzed on a per-lesion basis. A marginal Cox model accounted for correlated data in patients with multiple lesions, and a model to predict per-lesion outcomes was adjusted for confounding factors. RESULTS: For deferred lesions, the risk of major adverse cardiac events demonstrated a significant, inverse relationship with FFR (adjusted hazard ratio, 1.06; 95% confidence interval, 1.05-1.08; P<0.001). However, this relationship was not observed in revascularized lesions (adjusted hazard ratio, 1.00; 95% confidence interval, 0.98-1.02; P=0.70). For lesions with FFR ≥0.76, the risk of major adverse cardiac events was not significantly different between deferred and revascularized lesions. Conversely, in lesions with FFR ≤0.75, the risk of major adverse cardiac events was significantly lower in revascularized lesions than in deferred lesions (for FFR 0.71-0.75, adjusted hazard ratio, 0.47; 95% confidence interval, 0.24-0.89; P=0.021; for FFR ≤0.70, adjusted hazard ratio 0.47; 95% confidence interval, 0.26-0.84; P=0.012). CONCLUSIONS: This large, prospective registry showed that the FFR value was linearly associated with the risk of cardiac events in deferred lesions. In addition, revascularization for coronary artery stenosis with a low FFR (≤0.75) was associated with better outcomes than the deferral, whereas for a stenosis with a high FFR (≥0.76), medical treatment would be a reasonable and safe treatment strategy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01366404.

Machine learning assessment of myocardial ischemia using angiography: Development and retrospective validation.

BACKGROUND: Invasive fractional flow reserve (FFR) is a standard tool for identifying ischemia-producing coronary stenosis. However, in clinical practice, over 70% of treatment decisions still rely on visual estimation of angiographic stenosis, which has limited accuracy (about 60%-65%) for the prediction of FFR < 0.80. One of the reasons for the visual-functional mismatch is that myocardial ischemia can be affected by the supplied myocardial size, which is not always evident by coronary angiography. The aims of this study were to develop an angiography-based machine learning (ML) algorithm for predicting the supplied myocardial volume for a stenosis, as measured using coronary computed tomography angiography (CCTA), and then to build an angiography-based classifier for the lesions with an FFR < 0.80 versus ≥ 0.80. METHODS AND FINDINGS: A retrospective study was conducted using data from 1,132 stable and unstable angina patients with 1,132 intermediate lesions who underwent invasive coronary angiography, FFR, and CCTA at the Asan Medical Center, Seoul, Korea, between 1 May 2012 and 30 November 2015. The mean age was 63 ± 10 years, 76% were men, and 72% of the patients presented with stable angina. Of these, 932 patients (assessed before 31 January 2015) constituted the training set for the algorithm, and 200 patients (assessed after 1 February 2015) served as a test cohort to validate its diagnostic performance. Additionally, external validation with 79 patients from two centers (CHA University, Seongnam, Korea, and Ajou University, Suwon, Korea) was conducted. After automatic contour calibration using the caliber of guiding catheter, quantitative coronary angiography was performed using the edge-detection algorithms (CAAS-5, Pie-Medical). Clinical information was provided by the Asan BiomedicaL Research Environment (ABLE) system. The CCTA-based myocardial segmentation (CAMS)-derived myocardial volume supplied by each vessel (right coronary artery [RCA], left anterior descending [LAD], left circumflex [LCX]) and the myocardial volume subtended to a stenotic segment (CAMS-%Vsub) were measured for labeling. The ML for (1) predicting vessel territories (CAMS-%LAD, CAMS-%LCX, and CAMS-%RCA) and CAMS-%Vsub and (2) identifying the lesions with an FFR < 0.80 was constructed. Angiography-based ML, employing a light gradient boosting machine (GBM), showed mean absolute errors (MAEs) of 5.42%, 8.57%, and 4.54% for predicting CAMS-%LAD, CAMS-%LCX, and CAMS-%RCA, respectively. The percent myocardial volumes predicted by ML were used to predict the CAMS-%Vsub. With 5-fold cross validation, the MAEs between ML-predicted percent myocardial volume subtended to a stenotic segment (ML-%Vsub) and CAMS-%Vsub were minimized by the elastic net (6.26% ± 0.55% for LAD, 5.79% ± 0.68% for LCX, and 2.95% ± 0.14% for RCA lesions). Using all attributes (age, sex, involved vessel segment, and angiographic features affecting the myocardial territory and stenosis degree), the ML classifiers (L2 penalized logistic regression, support vector machine, and random forest) predicted an FFR < 0.80 with an accuracy of approximately 80% (area under the curve [AUC] = 0.84-0.87, 95% confidence intervals 0.71-0.94) in the test set, which was greater than that of diameter stenosis (DS) > 53% (66%, AUC = 0.71, 95% confidence intervals 0.65-0.78). The external validation showed 84% accuracy (AUC = 0.89, 95% confidence intervals 0.83-0.95). The retrospective design, single ethnicity, and the lack of clinical outcomes may limit this prediction model's generalized application. CONCLUSION: We found that angiography-based ML is useful to predict subtended myocardial territories and ischemia-producing lesions by mitigating the visual-functional mismatch between angiographic and FFR. Assessment of clinical utility requires further validation in a large, prospective cohort study.

Trial of everolimus-eluting stents or bypass surgery for coronary disease.

BACKGROUND: Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents. METHODS: We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups. RESULTS: After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG. CONCLUSIONS: Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).

Comparison of drug-eluting stents and drug-coated balloon for the treatment of drug-eluting coronary stent restenosis: A randomized RESTORE trial.

BACKGROUND: This study sought to evaluate the optimal treatment for in-stent restenosis (ISR) of drug-eluting stents (DESs). METHODS: This is a prospective, multicenter, open-label, randomized study comparing the use of drug-eluting balloon (DEB) versus second-generation everolimus-eluting stent for the treatment of DES ISR. The primary end point was in-segment late loss at 9-month routine angiographic follow-up. RESULTS: A total of 172 patients were enrolled, and 74 (43.0%) patients underwent the angiographic follow-up. The primary end point was not different between the 2 treatment groups (DEB group 0.15±0.49 mm vs DES group 0.19±0.41 mm, P=.54). The secondary end points of in-segment minimal luminal diameter (MLD) (1.80±0.69 mm vs 2.09±0.46 mm, P=.03), in-stent MLD (1.90±0.71 mm vs 2.29±0.48 mm, P=.005), in-segment percent diameter stenosis (34%±21% vs 26%±15%, P=.05), and in-stent percent diameter stenosis (33%±21% vs 21%±15%, P=.002) were more favorable in the DES group. The composite of death, myocardial infarction, or target lesion revascularization at 1 year was comparable between the 2 groups (DEB group 7.0% vs DES group 4.7%, P=.51). CONCLUSIONS: Treatment of DES ISR using DEB or second-generation DES did not differ in terms of late loss at 9-month angiographic follow-up, whereas DES showed better angiographic results regarding minimal MLD and percent diameter stenosis. Both treatment strategies were safe and effective up to 1year after the procedure.

Comparison of long-term mortality according to obesity in patients with successful percutaneous chronic total occlusion interventions using drug-eluting stents.

OBJECTIVE: To evaluate the long-term mortality according to obesity in patients with chronic total occlusion (CTO) lesions after successful percutaneous coronary intervention (PCI). BACKGROUND: Despite the potential impact of coronary revascularization and lesion severity on the obesity paradox, the long-term survival according to obesity in CTO patients after successful PCI has been unknown. METHODS AND RESULTS: Between January 2003 and September 2014, we examined 1,172 consecutive Korean patients with 1,190 CTO lesions who underwent successful drug-eluting stent (DES) implantation in two tertiary academic medical centers. The primary and secondary endpoints were all-cause and cardiac death, respectively. Obesity was defined as a body mass index ≥25.0 kg/m2 , based on the criteria for Asians. The median follow-up time was 4.4 years. The prevalence of obesity was 54.4%. During the follow-up periods, the occurrence of all-cause (6.1 vs. 10.7%) and cardiac death (3.8 vs. 6.7%) was lower in obese patients than in non-obese patients (P <0.05, respectively). Kaplan-Meier analysis showed that obese patients had lower cumulative rates of all-cause and cardiac death than did non-obese patients (log-rank P <0.05, respectively). Univariate Cox regression analysis showed that age ≥65 years (hazard ratio [HR], 3.62), diabetes mellitus (HR, 1.94), renal dysfunction (HR, 7.03), systolic heart failure (HR, 2.61), and obesity (HR, 0.58) were associated with all-cause death (P <0.05). Multivariate Cox regression models showed that high BMI was independently associated with the decreased risk of all-cause death. CONCLUSIONS: Obese patients appear to have a lower long-term mortality than do non-obese patients in CTO after successful PCI using DES. © 2017 Wiley Periodicals, Inc.

Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma: a section-to-section comparison study.

OBJECTIVES: To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA)-a precursor of plaque rupture-defined by optical coherence tomography (OCT) in a section-to-section-level comparison. METHODS: From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. RESULTS: OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm2). CONCLUSIONS: LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. KEY POINTS: • CT-defined LAP and NRS were associated with OCT-defined TCFA • OCT-TCFA showed higher frequency of LAP, NRS, PR and greater plaque burden • Non-calcified plaque area was correlated with OCT-measured lipid arc.

Fractional flow reserve and pressure-bounded coronary flow reserve to predict outcomes in coronary artery disease.

AIMS: Fractional flow reserve (FFR) has proven to its prognostic and therapeutic value. However, the additive prognostic value of coronary flow reserve (CFR) remains unclear. This study sought to investigate the clinical utility of combined FFR and CFR measurements to predict outcomes. METHODS AND RESULTS: Using the prospective, multicentre Interventional Cardiology Research Incooperation Society-FFR registry, a total of 2088 lesions from 1837 patients were included in this substudy. Based on baseline and hyperaemic pressure gradients, we computed physiologic limits of CFR [the so called pressure-bounded (pb) CFR] and classified lesions as low (<2) or high (≥2). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction, and revascularization) analysed on a per-patient basis. During a median follow-up of 1.9 years (inter-quartile range: 1.0-3.0 years), MACE occurred in 5.7% of patients with FFR ≤0.80 vs. 2.8% of patients with FFR >0.80 [adjusted hazard ratio (aHR): 2.15, 95% confidence interval (CI): 1.19-3.89; P = 0.011. In contrast, the incidence of MACE did not differ between patients with pb-CFR < 2 vs. pb-CFR ≥ 2 (4.2% vs. 4.2%; aHR: 0.98, CI: 0.60 to 1.58; P = 0.92). Incorporation of FFR significantly improved model prediction of MACE (global χ2 38.8-48.1, P = 0.002). However, pb-CFR demonstrated no incremental utility to classify outcomes (global χ2 48.1-48.2, P > 0.99). CONCLUSIONS: In this large, prospective registry of over 2000 coronary lesions, FFR was strongly associated with clinical outcomes. In contrast, a significant association between pb-CFR and clinical events could not be determined and adding knowledge of pb-CFR did not improve prognostication over FFR alone.

Long-term outcomes of bypass grafting versus drug-eluting stenting for left main coronary artery disease: Results from the IRIS-MAIN registry.

There are limited data on comparative outcomes and its determinants following coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for left main coronary artery disease (LMCAD) in a real-world setting. METHODS: A total of 3,504 consecutive patients with LMCAD treated with CABG (n=1,301) or PCI with DES (n=2,203) from the IRIS-MAIN registry were analyzed. The relative treatment effect of one strategy over another was assessed by propensity-score matching method. The primary outcome was a composite of death, myocardial infarction, or stroke. RESULTS: Median follow-up duration was 4.7 years. In the matched cohort, both groups demonstrated a similar risk for the primary outcome (adjusted hazard ratio [HR]: 0.94; 95% CI: 0.77-1.15; P=.54). Compared with CABG, PCI exhibited higher risks of myocardial infarction (HR: 2.11; 95% CI: 1.16-3.83; P=.01) and repeated revascularization (HR: 5.95; 95% CI: 3.94-8.98; P<.001). In the overall population, age, presence of chronic kidney disease, and low ejection fraction (<40%) were key clinical predictors of primary outcome regardless of the treatment strategy. However, factors deemed to be associated with perioperative morbidity were determinants of primary outcome in the CABG group, whereas those generally associated with the severity of atherosclerotic coronary artery disease were strong predictors in the PCI group. CONCLUSIONS: Among patients with significant LMCAD, the long-term risk of the composite outcome of death, myocardial infarction, or stroke was similar between CABG and PCI. Clinical variables that differentially predict adverse outcomes might be useful in triaging appropriate revascularization strategy.

Predictors of long-term outcomes after bypass grafting versus drug-eluting stent implantation for left main or multivessel coronary artery disease.

BACKGROUND: We assessed predictors of long-term outcomes after coronary artery bypass grafting (CABG) versus those after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,230 patients with left main or multivessel coronary artery disease (CAD). METHODS AND RESULTS: Data were pooled from the BEST, PRECOMBAT, and SYNTAX trials. Age, chronic kidney disease, chronic obstructive lung disease, left ventricular dysfunction, and peripheral arterial disease (PAD) were common predictors of all-cause mortality. Diabetes mellitus, previous myocardial infarction (MI), and SYNTAX score were independent predictors of all-cause mortality in the PCI group, but not in the CABG group. In the CABG group, age was the only risk factor for MI; left ventricular dysfunction, hypertension, and PAD were risk factors for stroke. On the other hand, in the PCI group, incomplete revascularization and previous MI were risk factors for MI; age and previous stroke for stroke. In addition, chronic kidney disease significantly correlated with a composite outcome of death, MI, or stroke in the CABG group, and incomplete revascularization and previous MI in the PCI group. CONCLUSIONS: Simple clinical variables and SYNTAX score differentially predict long-term outcomes after CABG versus those after PCI with DES for left main or multivessel CAD. Those predictors might help to guide the choice of revascularization strategy. © 2017 Wiley Periodicals, Inc.

Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials.

AIMS: Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations, with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascular mortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirin alone in high-risk patients with a history of prior myocardial infarction (MI). METHODS AND RESULTS: A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67-0.90; P = 0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74-0.98; P = 0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86-1.23; P = 0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83-1.03; P = 0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55-0.88; P = 0.003), stroke (RR 0.81, 95% CI 0.68-0.97; P = 0.02), and stent thrombosis (RR 0.50, 95% CI 0.28-0.89; P = 0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19-2.50; P = 0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53-1.58; P = 0.75). CONCLUSION: Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death.

Complete versus incomplete revascularization in patients with multivessel coronary artery disease treated with drug-eluting stents.

BACKGROUND: The clinical impact of completeness of revascularization on adverse cardiovascular events remains unclear among patients with multivessel coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: This analysis included consecutive patients with multivessel CAD, who underwent PCI with drug-eluting stents (DES) during the period from January 1, 2003, through to December 31, 2013. We compared the outcomes in patients, who achieved complete (CR) versus incomplete revascularization (IR) at the time of PCI. The primary outcome was death from any cause. Secondary outcomes were the rates of myocardial infarction (MI), stroke, and repeat revascularization. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. RESULTS: Among 3901 patients with multivessel CAD treated with DES, 1402 pairs of similar propensity scores in each group of CR and IR were identified. At a median follow-up of 4.9 years (interquartile range, 2.4-7.5), IR was associated with a similar risk of death (hazard ratio [HR], 1.03; 95% CI, 0.80-1.32; P=.83) as compared with CR. IR was also associated with similar risks of stroke (HR, 1.26; 95% CI, 0.76-2.09; P=.37) and repeat revascularization (HR, 1.15; 95% CI, 0.93-1.41; P=.19), but associated with a higher risk of MI (HR, 1.86; 95% CI, 1.08-3.19; P=.024) compared to CR. CONCLUSIONS: Among patients with multivessel CAD treated with DES, as compared with CR, IR was associated with similar risk of death. However, IR was associated with a higher risk of MI during follow-up.

Multimodality imaging of attenuated plaque using grayscale and virtual histology intravascular ultrasound and optical coherent tomography.

BACKGROUND: Although attenuated plaque is a marker for plaque vulnerability, the quantification and its implication have not been known. METHODS: Multimodality pre-procedural imaging using grayscale intravascular ultrasound (IVUS), virtual histology-IVUS (VH-IVUS), and optical coherence tomography (OCT) were performed in 115 coronary lesions with diameter stenosis (DS) >30% and plaque burden ≥50% and compared the diagnostic accuracies for detecting thin-cap fibroatheromas (TCFA). RESULTS: A maximal arc of attenuation (40 MHz IVUS) ≥29.0° was the cutoff for predicting VH-TCFA (sensitivity 74%, specificity 66%); and OCT-TCFA (sensitivity 89%, specificity 64%), while a maximal arc attenuation ≥29.0° (20MHz IVUS) showed a poor sensitivity for predicting TCFA. Compared to the lesions with an arc of attenuation <30° as a rough cutoff value, the lesions with a maximum arc of attenuation ≥30° (40 MHz) were associated with more severe (smaller angiographic minimum lumen diameter and greater DS, smaller IVUS-MLA and a larger plaque burden) and had more unstable lesion characteristics: (1) larger remodeling index and more plaque ruptures (grayscale IVUS); (2) greater %necrotic core and more VH-TCFAs (VH-IVUS); and (3) more lipid, macrophages, cholesterol crystals, and microchannels; thinner fibrous caps; and more OCT-TCFAs, OCT-detected plaque ruptures, and red and white thrombi (OCT). Among 58 patients treated with stent implantation, postintervention peak CK-MB was higher in patients with the maximal attenuation ≥30° compared to those without (median 2.7 ng/ml [IQR 0.9-18.7 ng/ml] vs. median 0.9 ng/ml [IQR 0.7-2.1 ng/ml], P = 0.012). CONCLUSION: Attenuated plaque with a maximal attenuation ≥30° vs. <30° (40 MHz, but not 20 MHz IVUS) were more likely to be associated with unstable lesion morphology that may contribute to the immediate poststenting CK-MB elevation. © 2016 Wiley Periodicals, Inc.