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.

Preventive PCI or medical therapy alone for vulnerable atherosclerotic coronary plaque: Rationale and design of the randomized, controlled PREVENT trial.

BACKGROUND: Acute coronary syndromes are commonly caused by the rupture of vulnerable plaque, which often appear angiographically not severe. Although pharmacologic management is considered standard therapy for stabilizing plaque vulnerability, the potential role of preventive local treatment for vulnerable plaque has not yet been determined. The PREVENT trial was designed to compare preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) with OMT alone in patients with functionally nonsignificant high-risk vulnerable plaques. METHODS: The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized trial. Eligible patients have at least 1 angiographically significant stenosis (diameter stenosis >50% by visual estimation) without functional significance (fractional flow reserve [FFR] >0.80). Target lesions are assessed by intracoronary imaging and must meet at least 2 imaging criteria for vulnerable plaque; (1) minimal lumen area <4.0 mm2; (2) plaque burden >70%; (3) maximal lipid core burden index in a 4 mm segment >315 by near infrared spectroscopy; and (4) thin cap fibroatheroma as determined by virtual histology or optical coherence tomography. Enrolled patients are randomly assigned in a 1:1 ratio to either preventive PCI with either bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is target-vessel failure, defined as the composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years after randomization. RESULTS: Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results are expected to be available in early 2024. CONCLUSIONS: The PREVENT trial is the first large-scale, randomized trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaques containing multiple high-risk features that is appropriately powered for clinical outcomes. PREVENT will provide compelling evidence as to whether preventive PCI of vulnerable plaques plus OMT improves patient outcomes compared with OMT alone. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02316886. KEY POINTS: The PREVENT trial is the first, large-scale randomized clinical trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. It will provide compelling evidence to determine whether PCI of focal vulnerable plaques on top of OMT improves patient outcomes.

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.

Different Clinical Features between Definite and Possible Takotsubo Syndrome in a Tertiary Referral Hospital.

BACKGROUND: Although imaging examination to exclude coronary artery disease (CAD) is an indispensable step for a definite diagnosis of takotsubo syndrome (TTS), this step may be overlooked in a substantial proportion of patients with secondary TTS admitted to a tertiary hospital. However, the clinical profiles and outcomes of these patients with "possible TTS" have rarely been investigated. METHODS: Among 420 consecutive TTS patients with characteristic transient ventricular ballooning on repeated echocardiography, 244 patients (58.1%) who underwent an imaging study for CAD were diagnosed with "definite TTS," whereas the remaining 176 were designated with "possible TTS." RESULTS: Overall, hypoxia (67.6%) and dyspnea (55.5%) were predominant presentations. The possible group was characterized by higher prevalence of male gender (46.6% vs. 35.2%, p = 0.019), secondary TTS (97.2% vs. 86.5%, p < 0.001), cancer (43.2% vs. 29.1%, p = 0.003), sepsis (46.0% vs. 32.0%, p = 0.003), and nonapical ballooning pattern (30.7% vs. 21.3%, p = 0.001) with less common ST-segment elevation on electrocardiogram (18.8% vs. 34.0%, p = 0.001). The possible group showed higher frequency of mechanical ventilation (56.2% vs. 40.2%, p = 0.001), pulmonary edema (72.2% vs. 61.5%, p = 0.023), and shock management (70.5% vs. 54.1%, p = 0.001) with similar in-hospital mortality (17.2% vs. 17.0%, p = 0.964). CONCLUSIONS: In real-world clinical practice, coronary evaluation for strict diagnosis of TTS is not frequently feasible. Addition of the possible group without coronary evaluation to the clinical spectrum of TTS would be helpful for fair estimation of clinical implication of TTS.

Ten-Year Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow-Up of the PRECOMBAT Trial.

BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents and coronary-artery bypass grafting (CABG) for left main coronary artery disease are highly debated. METHODS: In the PRECOMBAT trial (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), patients with unprotected left main coronary artery disease were randomly assigned to undergo PCI with sirolimus-eluting stents (n=300) or CABG (n=300) in 13 hospitals in Korea from April 2004 to August 2009. The follow-up was extended to at least 10 years for all patients (median, 11.3 years). The primary outcome was the incidence of major adverse cardiac or cerebrovascular events (composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization). RESULTS: At 10 years, a primary outcome event occurred in 29.8% of the PCI group and in 24.7% of the CABG group (hazard ratio [HR] with PCI vs CABG, 1.25 [95% CI, 0.93-1.69]). The 10-year incidence of the composite of death, myocardial infarction, or stroke (18.2% vs 17.5%; HR 1.00 [95% CI, 0.70-1.44]) and all-cause mortality (14.5% vs 13.8%; HR 1.13 [95% CI, 0.75-1.70]) were not significantly different between the PCI and CABG groups. Ischemia-driven target-vessel revascularization was more frequent after PCI than after CABG (16.1% vs 8.0%; HR 1.98 [95% CI, 1.21-3.21). CONCLUSIONS: Ten-year follow-up of the PRECOMBAT trial of patients with left main coronary artery disease randomized to PCI or CABG did not demonstrate significant difference in the incidence of major adverse cardiac or cerebrovascular events. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03871127 and NCT00422968.

Comparison of simple versus complex stenting in patients with true distal left main bifurcation lesions.

INTRODUCTION: Distal left main (LM) bifurcation disease is one of the most challenging lesion subsets for percutaneous coronary intervention (PCI) and optimal stenting strategy for such complex lesions is still debated. This study aimed to compare clinical outcomes following single versus dual stenting for true distal LM bifurcation lesions. METHODS: Patients with true distal LM bifurcation lesions (type 1,1,1 or 0,1,1: both left anterior descending and circumflex artery >2.5 mm diameter) receiving PCI with drug-eluting stents (DES) from two large clinical registries were evaluated. The primary outcome was target-lesion failure (TLF), defined as a composite of cardiac death, target-vessel myocardial infarction (MI), or target-lesion revascularization (TLR). Outcomes were compared with the use of propensity scores and inverse probability-weighting adjustment to reduce treatment selection bias. RESULTS: Among 1,002 patients undergoing true distal LM PCI, 440 (43.9%) and 562 (56.1%) were treated with single and dual stents, respectively. The TLF rates at 3 year was 20.3% in the single-stent group and 24.1% in the dual-stenting group (log-rank p = 0.18). The adjusted risk for TLF did not differ significantly between two groups (hazard ratio [HR] with dual-stent vs. single-stent: 1.27, 95% confidence interval [CI]: 0.95-1.71). The adjusted risks for death, MI, repeat revascularization, or stent thrombosis were also similar between the single- and dual-stenting groups. CONCLUSIONS: In patients undergoing PCI for true distal LM disease, single- and dual-stent strategies showed a similar adjusted risk of TLF at 3 years. Our findings should be confirmed or refuted through large, randomized clinical trials.

Ten-year outcomes of early generation sirolimus- versus paclitaxel-eluting stents in patients with left main coronary artery disease.

To compare 10-year outcomes after implantation of sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES) for left main coronary artery (LMCA) stenosis. Very long-term outcome data of patients with LMCA disease treated with drug-eluting stents (DES) have not been well described. In 10-year extended follow-up of the MAINCOMPARE registry, we evaluated 778 patients with unprotected LMCA stenosis who were treated with SES (n = 607) or PES (n = 171) between January 2000 and June 2006. The primary composite outcome (a composite of death, myocardial infarction [MI] or target-vessel revascularization [TVR]) was compared with an inverse-probability-of-treatment-weighting (IPTW) adjustment. Clinical events have linearly accumulated over 10 years. At 10 years, there were no significant differences between SES and PES in the observed rates of the primary composite outcome (42.0% vs. 47.4%; hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.66-1.10), and definite stent thrombosis (ST) (1.9% vs. 1.8%; HR 1.02, 95% CI 0.28-3.64). In the IPTW-adjusted analyses, there were no significant differences between SES and PES in the risks for the primary composite outcome (HR 0.89, 95% CI 0.65-1.14) or definite ST (adjusted HR 1.05, 95% CI 0.29-3.90). In patients who underwent DES implantation, high overall adverse clinical event rates (with a linearly increasing event rate over time) were observed during extended follow-up. At 10 years, there were no measurable differences in outcomes between patients treated with SES vs. PES for LMCA disease. The incidence of stent thrombosis was quite low and comparable between the groups.

Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke.

Importance: Patent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, the best treatment for any individual is often unclear. Objective: To evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems. Design, Setting, and Participants: Investigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. Exposures: PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10-point scoring system in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) Classification System, which combines the RoPE Score with high-risk PFO features (either an atrial septal aneurysm or a large-sized shunt) to classify patients into 3 categories of causal relatedness: unlikely, possible, and probable. Main Outcomes and Measures: Ischemic stroke. Results: Over a median follow-up of 57 months (IQR, 24-64), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%) (adjusted hazard ratio [HR], 0.41 [95% CI, 0.28-0.60]). The subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE Score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified as unlikely, possible, and probable using the PASCAL Classification System had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was -0.7% (95% CI, -4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 after randomization with a device were 4.41% (95% CI, 1.02% to 7.80%), 1.53% (95% CI, 0.33% to 2.72%), and 0.65% (95% CI, -0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively. Conclusions and Relevance: Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of this classification system has the potential to guide individualized decision-making.

Clinical Outcome of Rotational Atherectomy in Calcified Lesions in Korea-ROCK Registry.

Background and Objectives: Data is still limited regarding clinical outcomes of rotational atherectomy (RA) after percutaneous coronary intervention. We sought to evaluate clinical outcomes of RA. Materials and Methods: This multi-center registry enrolled patients who underwent RA during PCI from nine tertiary centers in Korea between January 2010 and October 2019. The primary endpoint was target-vessel failure (TVF; the composite outcome of cardiac death, target-vessel spontaneous myocardial infarction, or target-vessel revascularization). Results: Of 540 patients (583 lesions), the mean patient age was 71.4 ± 0.4 years, 323 patients (59.8%) were men, and 305 patients (56.5%) had diabetes mellitus. Technical success rate was 96.4%. In-hospital major adverse cerebral and cardiac events occurred in 63 cases (10.8%). At 1.5 years, 72 (16.0%) of TVFs were occurred. We evaluated independent predictors of TVF, which included current smoker (hazard ratio (HR), 1.92; 95% confidence interval (CI), 1.17-3.16; p = 0.01), chronic renal disease (HR, 1.87; 95% CI, 1.14-3.08; p = 0.013), history of cerebrovascular attack (HR, 2.14; 95% CI, 1.24-3.68; p = 0.006), left ventricle ejection fraction (HR, 0.98; 95% CI, 0.97-0.999; p = 0.037), and left main disease (HR, 1.94; 95% CI, 1.11-3.37; p = 0.019). Conclusions: From this registry, we demonstrated acceptable success rates, in-hospital and mid-term clinical outcomes of RA in the DES era.

Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial.

BACKGROUND: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. METHODS: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. RESULTS: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P=0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P=0.04) and fatal bleeding (1% [4/400] vs 0%, P=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. CONCLUSIONS: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.

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.

Comparison of optical coherence tomography-guided versus intravascular ultrasound-guided percutaneous coronary intervention: Rationale and design of a randomized, controlled OCTIVUS trial.

BACKGROUND: The clinical value of intracoronary imaging for percutaneous coronary intervention (PCI) guidance is well acknowledged. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the most commonly used intravascular imaging to guide and optimize PCI in day-to-day practice. However, the comparative effectiveness of IVUS-guided versus OCT-guided PCI with respect to clinical end points remains unknown. METHODS AND DESIGN: The OCTIVUS study is a prospective, multicenter, open-label, parallel-arm, randomized trial comparing the effectiveness of 2 imaging-guided strategies in patients with stable angina or acute coronary syndromes undergoing PCI in Korea. A total of 2,000 patients are randomly assigned in a 1:1 ratio to either an OCT-guided PCI strategy or an IVUS-guided PCI strategy. The trial uses a pragmatic comparative effectiveness design with inclusion criteria designed to capture a broad range of real-world patients with diverse clinical and anatomical features. PCI optimization criteria are predefined using a common algorithm for online OCT or IVUS. The primary end point, which was tested for both noninferiority (margin, 3.1 percentage points for the risk difference) and superiority, is target-vessel failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization) at 1 year. RESULTS: Up to the end of July 2020, approximately 1,200 "real-world" PCI patients have been randomly enrolled over 2 years. Enrollment is expected to be completed around the midterm of 2021, and primary results will be available by late 2022 or early 2023. CONCLUSION: This large-scale, multicenter, pragmatic-design clinical trial will provide valuable clinical evidence on the relative efficacy and safety of OCT-guided versus IVUS-guided PCI strategies in a broad population of patients undergoing PCI in the daily clinical practice.

Pragmatic trial comparing routine versus no routine functional testing in high-risk patients who underwent percutaneous coronary intervention: Rationale and design of POST-PCI trial.

BACKGROUND: Although the need to detect restenosis has diminished in the contemporary practice of percutaneous coronary intervention (PCI) with drug-eluting stents (DES), the surveillance of ischemia owing to restenosis or disease progression deserves attention in high-risk PCI settings. It is unknown whether follow-up strategy of routine noninvasive functional testing potentially reduces the risk of major cardiovascular events in high-risk PCI patients. METHODS: The POST-PCI study is an investigator-initiated, multicenter, prospective randomized trial comparing the effectiveness of two follow-up strategies in patients with high-risk anatomic or clinical characteristics who underwent PCI. Study participants were randomly assigned to either (1) the routine noninvasive stress testing (exercise electrocardiography, nuclear stress imaging, or stress echocardiography) at 12 months post-PCI or (2) the standard-care without routine testing. In the routine stress testing group, depending on the testing results, all clinical decisions regarding subsequent diagnostic or therapeutic procedures were at the treating physician's discretion. The primary endpoint was a composite outcome of death from any causes, myocardial infarction, or hospitalization for unstable angina at 2 years post-PCI. RESULTS: More than 1700 high-risk PCI patients have been randomized over 2.0 years at 11 major cardiac centers in Korea. CONCLUSION: This pragmatic POST-PCI trial will provide valuable clinical evidence on the effectiveness of follow-up strategy of routine noninvasive stress testing in high-risk PCI patients.

Long-term (10-year) outcomes of stenting or bypass surgery for acute coronary syndromes and stable ischemic heart disease with unprotected left main coronary artery disease.

BACKGROUND: Acuity of clinical presentation may influence decision making of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease. However, it is undetermined whether clinical indication for myocardial revascularization may affect the relative long-term effect after PCI and CABG. METHODS: In the MAIN-COMPARE study including 2,240 patients with LMCA disease treated with PCI (n = 1102) or CABG (n = 1138), we examined interaction between acuity of clinical presentation (acute coronary syndromes [ACS] or non-ACS) and revascularization strategy on 10-year outcomes. Primary outcome was a composite of all-cause death, Q-wave myocardial infarction, or stroke. Secondary outcomes were all-cause death or target vessel revascularization. RESULTS: In overall patients, 1,603 patients (71.6%) presented with ACS and 637 patients (28.4%) presented with non-ACS. The 10-year adjusted risks for primary composite outcome were similar after PCI and CABG among patients who presented with non-ACS (hazard ratio [HR] 1.07; 95% CI 0.71-1.61) and those who presented with ACS (HR 1.00; 95% CI 0.81-1.24) (P for interaction = .29). The adjusted risks of death were also similar between 2 groups in non-ACS (HR 0.98; 95% CI 0.63-1.51) and ACS (HR 1.02; 95% CI 0.81-1.28) patients (P for interaction = .62). The adjusted risks of target vessel revascularization were consistently higher after PCI in non-ACS (HR 6.38; 95% CI 3.14-12.96) and ACS (HR 3.96; 95% CI 2.80-5.60) patients (P for interaction = .39). CONCLUSIONS: In patients with LMCA disease, we have identified no significant interaction between the acuity of clinical indication and the relative treatment effect of PCI versus CABG on 10-year clinical outcomes.

Long-term trends of treatment effect of stenting or bypass surgery in patients with ostial or shaft left main coronary artery disease.

BACKGROUND: Little is known about how the relative treatment effect of percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG) on clinical outcomes in ostial or shaft left main coronary artery (LMCA) disease has evolved over time. METHODS: This study included 2,112 patients with ostial or shaft LMCA disease from IRIS-MAIN registry who underwent PCI (n = 1,329) or CABG (n = 783). Patients were stratified by time period based on stent type availability: wave 1 (1995-2002, bare-metal stent [BMS] era); wave 2 (2003-2006, first-generation drug-eluting stent [DES] era); and wave 3 (2007-2014, second-generation DES era). RESULTS: Compared to CABG, PCI has been used more frequently from wave 1 to wave 3. PCI showed substantial improvements over time with respect to death (P for trend = 0.012); the composite of death, myocardial infarction (MI), or stroke (P for trend = 0.047); repeat revascularization (P for trend < 0.001); and major adverse cardiac and cerebrovascular events (MACCE; a composite of death, MI, stroke, or repeat revascularization) (P for trend < 0.001). By contrast, outcomes of CABG remained relatively stable over time. The gap between the treatment effects of CABG vs PCI for MACCE has narrowed over time; the adjusted hazard ratios for CABG compared to PCI during wave 1, 2, and 3 were 0.41 (95% confidence interval [CI]: 0.22-0.76), 0.47 (95% CI: 0.31-0.71), and 0.78 (95% CI: 0.50-1.20), respectively. CONCLUSIONS: In patients with ostial or shaft LMCA disease, significant improvements in PCI outcomes resulted in a progressive decline in the gap between the outcomes of CABG and PCI.

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.

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.