Multiple Cities, Argentina

Comparison of Low-Intensity Statin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus (PROVE-DM)

Statins [3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA) inhibitors] decreases the risk of death and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). The cardiovascular benefits of high-intensity compared to low-intensity statin therapy are well demonstrated, and current guidelines recommend high-intensity statin therapy for high-risk patients with ASCVD . However, statin-related side effects are usually dose-dependent, and more frequent in patients receiving high-intensity statin therapy. A meta-analysis of 13 statin trials with 91,140 individuals reported that statin therapy is associated with an increased risk of developing diabetes mellitus (DM) over a 4-year period compared to patients randomized to placebo (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.02-1.17). The high-intensity statin was associated with an increased risk of new onset DM compared with low doses of statins (HR 1.22, 95% CI 1.15 to 1.29). In addition, meta-analysis of five intensive-dose statin trials suggested the likelihood of developing DM is also higher with high-intensity statins compared to moderate-intensity statins in 32,752 subjects over a mean follow-up of 4.9 years (OR 1.12; 95% CI 1.04-1.22). Prediabetes is a risk factor for ASCVD with a rapidly increasing prevalence worldwide (7.5% in 2019 and projected to reach 8.0% by 2030). Every year about 6.4-12.1% of these people develop diabetes and the risk increase further in the elderly, obese patients, and patients with metabolic syndrome. Considering that the risk of ASCVD increases even before the onset of DM, prediabetes patients need aggressive statin therapy for primary and secondary prevention. However, high-intensity therapy may increase the risk of new-onset DM, especially in patients with pre-diabetes. For this reason, caution is required in determining statin treatment strategies. An effectiveness of statins in reducing cardiovascular events depends on an absolute reduction in low-density lipoprotein (LDL) cholesterol levels and the duration of statin administration A combination therapy of low-dose statin and ezetimibe is an equivalent approach to high-dose statin therapy for decreasing LDL cholesterol level by 50% and achieving LDL cholesterol target level. This strategy is therefore considered attractive to reduce the risk of new-onset DM, and often used because of concerns regarding statin-induced diabetes in pre-diabetic patients. However, there are no data to compare the incidence of new onset DM as a pre-specified primary outcome between two lipid lowering strategies among prediabetic patients with ASCVD. Herein, we designed the study of comparison of low-intensity statin plus ezetimibe versus high-intensity statin therapy on risk of new-onset DM (PROVE-DM), a phase 4 trial involving patients with established atherosclerosis requiring lipid lowering (statin or ezetimibe) agents, comparing a regimen of high-intensity statin (rosuvastatin 20 mg) with the low intensity statin and ezetimibe (rosuvastatin 5 mg plus ezetimibe 10 mg)

Drug-Coated Balloon in Patients With High Bleeding Risk

Second-generation DES is the standard of care for patients with coronary artery disease who are deemed eligible for percutaneous coronary intervention (PCI). Despite many advantages, DES inevitably accompany disadvantages such as the occurrence of late stent thrombosis and the need for maintaining dual antiplatelet (DAPT) for certain period due to permanent vascular implant, which lead to both increased ischemic and bleeding events. As an alternative to DES, drug-coated balloon (DCB), a novel treatment strategy, which has benefit of having shorter DAPT maintenance duration due to the absence of metallic scaffolds and polymers, has been introduced. Based on meta-analysis based on many randomized clinical trials (RCT), its use has been established in in-stent restenosis of bare-metal stents (BMS) and DES. Furthermore, recently published RCT demonstrated efficacy and safety of DCB in de-novo coronary lesions in small vessels with reference vessel size<3.0mm. However, studies exploring the feasibility of DCB in de-novo coronary artery stenosis beyond small vessels are limited. Furthermore, there is scarce data comparing DCB with DES in patients with de-novo coronary artery stenosis and high bleeding risk (HBR), a situation in which long-term maintenance of DAPT is a clinical dilemma. In previous BASKET-SMALL 2 trial, DCB showed noninferiority to DES in patients with de-novo coronary artery stenosis and small vessel disease. However, this trial was conducted in non-HBR patients, and the number of participated patients was insufficient. In another RCT, DEBUT trial exclusively enrolled patients with HBR and de-novo coronary artery stenosis. Although the DEBUT trial showed superiority of DCB angioplasty over implantation of BMS to treat de-novo coronary artery stenosis in patients with HBR, the results could not be applicable in contemporary practice because BMS has been no longer in clinical use. Recently, multiple RCTs have proved short-term DAPT (1-3 months) has comparable efficacy to longer term DAPT in HBR patients using latest second-generation DES. On this background, the current trial aims to compare clinical outcomes between DCB and DES to treat de-novo coronary artery stenosis in patients with HBR receiving guideline-directed short-term DAPT.

A Phase 3 Study to Assess the Efficacy and Safety of PK101 in Patients With Knee Osteoarthritis

The primary purpose of this study is to evaluate the efficacy of PK101 compared with PK101-002 at Week 8 in osteoarthritis. Also evaluates the safety of PK101.

Clinical Impact of Intravascular Ultrasound-Based Artificial Intelligence Technologies (INNOVATE-PCI)

The aim of the study is to evaluate the performances and prognostic impact of coronary angiography & IVUS-based algorithms for decision making and stent optimization in a multicenter, prospective cohort. Between January 2020 and June 2025, a total of 3,000 patients who performed coronary angiography (± FFR) and have at least one coronary stenosis requiring PCI (as culprit) will be enrolled from 15 centers in South Korea. In addition, the deferred lesions with visual estimated diameter stenosis of >30% will be evaluated as non-culprits. Brief study design is as depicted in the following figure. Supervised ML algorithms include: 1) angiography- and IVUS-based algorithms for predicting FFR, 2) IVUS-based algorithm for plaque characterization, 3) IVUS-based algorithm for predicting stent expansion, and 4) post-stenting IVUS-based algorithm for predicting stent failure. In the prospective cohort, the performance of each model will be assessed. This registry trial composed of the treated (culprit) and the deferred (nonculprit) coronary lesions has two primary objectives as follow; 1) Primary objectives in treated (culprit) lesions is to see the impact of the integrated ML model on the development of culprit-related 2-year target vessel failure (TVF). 2) Primary objectives in deferred (nonculprit) lesions is to see the impact of the integrated ML model on the development of nonculprit-related 2-year TVF.

Anatomic Versus Physiologic Guidance for Complete Revascularization With DES Eluting in Patients With CAD

This is a prospective, multicenter center, open-label, randomized trial to compare QCA-guided versus FFR-guided CR strategies in patients with significant CAD who are undergoing PCI with DES. Patients with symptoms or evidence of myocardial ischemia are eligible for enrollment if there have stenotic lesions with a diameter stenosis of 50%-90% in major epicardial coronary arteries ≥ 2.25 mm in diameter by visual estimation, and CR is expected to be achievable by PCI. The detailed information for inclusion and exclusion criteria is described below in the session 4. Patients meeting inclusion criteria without any exclusion criteria will be randomized to either QCA-guided CR or FFR-guided CR group. In the QCA-guided CR group, PCI will be performed if there are lesions with diameter stenosis ≥ 50% by QCA during the index procedure (and, if necessary, planned staged procedure). In the FFR-guided CR group, FFR is measured for the target coronary lesions, and then PCI will be performed for the lesions with FFR ≤0.80. Post-PCI FFR measurement is strongly recommended. However, additional procedures are not recommended based on post-PCI FFR value because there is no consensus of the optimal cut-off value to define physiologic CR. In both QCA-guided and FFR-guided PCI groups, imaging guidance during PCI is left at the discretion of the operator. However, routine high pressure post-dilation with noncompliant balloons is recommended to achieve optimal stent expansion with minimal residual stenosis (diameter stenosis < 10% on visual estimation). Patients will be followed clinically at 1, 6, 12 months, and then upto 5 years after the index procedure

Tailored Versus Coventional AntiPlaTelet Strategy Intended After OPTIMIZEd Drug Eluting Stent

Objective: To assess the safety of tailored antiplatelet strategy (short DAPT followed by P2Y12 inhibitor alone) in patients who received optimized DES implantation guided by intravascular imaging (IVUS or OCT) Design: Prospective, open label, multi-center, dual arm, randomized trial Number of Subjects 3,944 subjects (1972:1972) Study Population: Patients with coronary artery disease undergoing imaging-guided PCI Study Design: - Eligible subjects will be randomized 1:1 to a) conventional DAPT strategy or b) tailored anti-platelet strategy (short DAPT followed by P2Y12 inhibitor alone) after optimized DES implantation guided by intravascular imaging. - All subjects will be clinically followed at 1, 6, and 12 months Co-primary Endpoints: 1. Clinically relevant bleeding (BARC 2, 3, or 5) at 12 months post-PCI 2. Ischemic composite adverse events of all-cause death, MI, ischemia-driven TVR, stent thrombosis at 12 months post-PCI 3. Net clinical outcome (NACE) of all-cause death, MI, ischemia-driven TVR, stent thrombosis, BARC 2,3,5 bleeding at 12 months post-PCI Statistics and Analysis: The study was designed to test the hypothesis that tailored antithrombotic strategy, as compared to the conventional DAPT, would be superior for clinically relevant bleeding, noninferior to the ischemic composite adverse events and NACE. The primary analysis would be evaluated by intention-to-treat analysis. With 3756 (each 1,878) patients, this study has >80% power to detect noninferiority of tailored antiplatelet strategy for ischemic composite adverse event, >85% power to detect noninferiority of tailored antiplatelet strategy for NACE, and >85% power to detect superiority of the tailored antiplatelet arm on clinically relevant bleeding. To compensate for 5% attrition rate, 3,944 (each 1,972) patients will be randomized.

Evaluation of Effectiveness and Safety of Ultimaster™ Tansei™ Stent in Routine Clinical Practice

Atrial Sensing Capability for Better Detection of Atrial Fibrillation

Implantable cardioverter defibrillators(ICD) therapy has been shown to reduce sudden cardiac death and improve survival in cardiac arrest survivors as well as in heart failure patients with left ventricular dysfunction. Atrial fibrillation (AF) is commonly found in ICD implantation patients up to 50%. AF is an independent predictor of mortality, inappropriate shock, and embolic events. Therefore, early detection of AF in patients with ICD is essential for improving the quality of life and overall prognosis of the patients. Conventional ICDs consist of a single chamber (SC) ICD with a lead only in the right ventricle (RV) and dual chamber (DC) ICD with each lead in the right atrium (RA) and RV. SC ICD has the advantage of shorter procedure time, lower cost compared to DC ICD. In contrast, DC ICD has the advantage of being able to monitor atrial arrhythmic events, but complication rates were higher and additional cost and longer procedure time are usually required than SC ICD. Sixty percent of ICD implantation patients who have are SC ICD Recently, a unique ICD lead with atrial sensing ring capable of monitoring the atrial electrical signals has been developed [Intica 7 VR-T DX ICD (Biotronik., Germany)]. Therefore, turning off the atrial sensing function makes it functionally the same as SC ICD whereas turning on makes it function similar to DC ICD without additional cost and procedure time. Therefore, Detection of AF could be made earlier with VDD ICD versus conventional SC ICD without atrial sensing capability, providing a better chance to improve the prognosis of ICD patients. However, no study exists which shows whether VDD ICD is better for detecting atrial tachyarrhythmia than conventional SC ICD. Therefore, we designed a multicenter prospective randomized study comparing the AF diagnostic efficacy of VDD ICD (with atrial sensing 'ON') against conventional SC ICD. As the second phase, we also plan to compare inappropriate therapy rate according to atrial sensing status of VDD ICD.

IRIS-Onyx Cohort in the IRIS-DES Registry

Implantable Cardioverter Defibrillator Versus Optimal Medical Therapy In Patients With Variant Angina Manifesting as Aborted Sudden Cardiac Death

All participants will be monitored over a span of five years and the time point of the year of last subject last visit. The term "year of last subject last visit" refers to the time point of the last visit for all participants. At this specific time point, event occurrence check will be conducted to determine the occurrence of endpoint events among all participants.