BACKGROUND:Despite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited. METHODS:In this open-label superiority trial conducted in South Korea, we randomly assigned patients with atherosclerotic cardiovascular disease in a 1:1 ratio to a target LDL cholesterol level of less than 55 mg per deciliter (1.4 mmol per liter) (intensive-targeting group) or less than 70 mg per deciliter (1.8 mmol per liter) (conventional-targeting group). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years. Safety was also assessed. RESULTS:Of 3048 patients who underwent randomization, 1526 were assigned to the intensive-targeting group and 1522 to the conventional-targeting group. The median follow-up was 3.0 years. The median LDL cholesterol level during the trial was 56 mg per deciliter (1.4 mmol per liter) in the intensive-targeting group and 66 mg per deciliter (1.7 mmol per liter) in the conventional-targeting group. A primary end-point event occurred in 100 patients (Kaplan-Meier estimate of cumulative incidence, 6.6%) in the intensive-targeting group and in 147 patients (Kaplan-Meier estimate of cumulative incidence, 9.7%) in the conventional-targeting group (hazard ratio, 0.67; 95% confidence interval, 0.52 to 0.86; P = 0.002). The incidence of prespecified safety end points was similar in the two trial groups, except for a lower incidence of creatinine elevation in the intensive-targeting group. CONCLUSIONS:Among patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg per deciliter resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70 mg per deciliter. (Funded by the Cardiovascular Research Center and Yuhan; Ez-PAVE ClinicalTrials.gov number, NCT04626973.).

Background Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) improves clinical outcomes through enhanced stent optimisation; however, whether these benefits extend to patients with multivessel disease (MVD), characterised by greater anatomical complexity and high ischaemic burden, remains unclear. Therefore, this study aimed to evaluate whether OCT guidance improves clinical outcomes in patients with MVD undergoing PCI. Methods We conducted a post hoc subgroup analysis of the OCCUPI trial, focusing on patients with MVD (diameter stenosis ≥50% in ≥2 major epicardial coronary arteries) with at least one complex lesion. The primary outcome was major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, stent thrombosis or ischaemia-driven target-vessel revascularisation over 1 year. Results Among the as-treated population in the OCCUPI trial (n=1604), 985 (61.4%) patients had MVD and 575 had single-vessel disease. In patients with MVD, OCT-guided PCI (n=515) was associated with a lower risk of 1-year MACE than angiography-guided PCI (n=470) (4.7% vs 8.9%; HR 0.51, 95% CI 0.31 to 0.85; p=0.008), with consistent treatment effects observed across disease extent (p for interaction=0.202). Among the OCT-guided patients, 355 (70.2%) achieved the prespecified OCCUPI optimisation criteria, whereas 151 (29.8%) did not. Stent optimisation was associated with significantly lower MACE rates (3.1% vs 8.6%; p=0.011) and consistent benefits were observed across MVD and single-vessel disease (p for interaction=0.521). Conclusions In patients with MVD and complex lesions, OCT-guided PCI was associated with a lower risk of 1-year MACE than angiography-guided PCI particularly when stent optimisation on OCT was achieved.

BACKGROUND:In patients with atrial fibrillation and chronic coronary syndrome beyond 12 months after percutaneous coronary intervention (PCI), oral anticoagulant monotherapy is recommended by the guideline; however, its efficacy and safety in patients with complex PCI remain uncertain. METHODS:We conducted a post hoc analysis of the randomized ADAPT AF-DES trial (Appropriate Duration of Antiplatelet and Thrombotic Strategy After 12 Months in Patients With Atrial Fibrillation Treated With Drug-Eluting Stents), which compared non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy with NOAC plus clopidogrel in patients with atrial fibrillation ≥12 months after second- or third-generation drug-eluting stent implantation. Complex PCI was defined by one of the following characteristics: ≥3 stents, ≥3 lesions, bifurcation with 2 stents, total stent length ≥60 mm, left main PCI, or chronic total occlusion PCI. Net adverse clinical events, ischemic composite outcomes, and bleeding composite outcomes were evaluated according to PCI complexity. RESULTS:Among 960 patients, 247 (25.7%) underwent complex PCI and 713 (74.3%) underwent noncomplex PCI. NOAC monotherapy was associated with a lower risk of net adverse clinical events compared with combination therapy in both the complex PCI group (9.5% versus 21.5%; hazard ratio, 0.42 [95% CI, 0.21-0.83]; P=0.01) and the noncomplex PCI group (9.6% versus 15.7%; hazard ratio, 0.59 [95% CI, 0.39-0.90]; P=0.02), with no significant interaction. Ischemic outcomes were infrequent and did not differ significantly between treatment strategies regardless of PCI complexity, whereas bleeding outcomes were consistently lower with NOAC monotherapy in both complex and noncomplex PCI groups. CONCLUSIONS:In this post hoc analysis of the randomized ADAPT AF-DES trial, NOAC monotherapy beyond 12 months after PCI was associated with a substantial reduction in bleeding regardless of PCI complexity. Although limited by low absolute event rates, ischemic outcomes did not differ significantly between treatment strategies. These findings suggest that a bleeding-focused long-term antithrombotic strategy may be reasonable in patients with atrial fibrillation and chronic coronary syndrome, including those with prior complex PCI, although prospective validation remains warranted. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04250116.

ABSTRACT BACKGROUND Peripheral artery disease (PAD) can lead to amputation in advanced cases, making cell therapy using human induced pluripotent stem cells (hiPSCs) a promising therapeutic option. hiPSC-derived endothelial cells (hiPSC-ECs) have shown favorable effects in treating experimental ischemic cardiovascular disease. An autologous approach for PAD patients is preferable to avoid immunological reactions. However, it is yet unknown whether hiPSCs and hiPSC-ECs derived from PAD patients have similar characteristics and potency compared to those derived from non-PAD donors. Therefore, we explored whether there are significant differences in the characteristics and potency of hiPSCs and hiPSC-ECs between non-PAD donors and PAD patients. METHODS We generated hiPSCs from the blood of non-PAD donors and patients with PAD. We determined the pluripotency of hiPSCs using qRT-PCR, flow cytometry, immunostaining, RNA-seq, and teratoma formation assay. The genetic stability of hiPSCs was confirmed by G-banding karyotyping. We then differentiated hiPSCs into endothelial cells (ECs) in a clinically compatible manner. We compared the characteristics and therapeutic potency of hiPSC-ECs derived from non-PAD and PAD groups using qRT-PCR, flow cytometry, immunostaining, and RNA-seq. In vitro endothelial functions were determined by nitric oxide (NO) production and capillary network formation. Therapeutic potency and incorporation of engrafted hiPSC-ECs were evaluated in a hindlimb ischemia model. RESULTS We successfully generated hiPSCs from the blood of seven non-PAD donors and eight PAD patients. Both non-PAD and PAD-derived hiPSCs exhibited similar expression levels of pluripotency markers. All hiPSCs, regardless of the group, formed teratomas and showed normal karyotypes. RNA-seq analyses revealed similar gene expression profiles between the groups. hiPSC-ECs derived from both non-PAD and PAD donors exhibited similar expression levels of EC markers at both the gene and protein levels. RNA-seq analyses showed no significant overall differences in gene expression profiles between the groups. Functional analyses demonstrated similar endothelial characteristics and function in hiPSC-ECs from both groups. Both groups showed similar perfusion recovery, limb salvage, and vessel-forming capacity. Engrafted hiPSC-ECs from both groups also exhibited similar angiogenic and vessel-forming capabilities. CONCLUSIONS Our study demonstrated no significant differences in hiPSCs and hiPSC-ECs derived from non-PAD donors and PAD patients in terms of molecular and cell biological characteristics, therapeutic effects, and vessel-forming capability. Our study indicates that hiPSCs and hiPSC-ECs derived from PAD patients can serve as a novel platform for autologous cell therapy.

The OCCUPI trial demonstrated the clinical benefit of optical coherence tomography (OCT)–guided percutaneous coronary intervention (PCI). However, whether the effect of OCT guidance differs according to diseased coronary vessel remains unclear. This prespecified substudy evaluated the consistency of clinical outcomes with OCT-guided PCI in left anterior descending (LAD) versus non-LAD lesions. Among 1,375 patients without left main disease, 888 had LAD lesions and 487 had non-LAD lesions. Patients were randomized to undergo PCI guided by either OCT or conventional angiography. The primary endpoint was 1-year major adverse cardiovascular events (MACE), defined as a composite of cardiac death, myocardial infarction, stent thrombosis, or ischemia-driven target-vessel revascularization (TVR). Outcomes were assessed by time-to-event analysis. In the LAD group, 1-year MACE occurred in 4.5 Clinical Outcomes According to Treatment Strategy Among 1,375 OCCUPI patients without left main disease, 1-year MACE did not significantly differ across OCT- vs angiography-guided PCI in LAD and non-LAD lesions (log-rank p = 0.229).

BACKGROUND:The clinical impact of optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) based on lesion characteristics remains unclear. OBJECTIVES:This study aimed to assess the impact of OCT-guided PCI for complex lesions on clinical outcomes according to lesion length and reference vessel diameter (RVD). METHODS:In the OCCUPI (Optical Coherence Tomography-guided Coronary Intervention in Patients with Complex Lesions) trial, 1,604 patients with complex lesions were classified according to the median lesion length (32 mm) and RVD (2.8 mm) measured by quantitative coronary angiography. The primary endpoint was the 1-year incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, stent thrombosis, or ischemia-driven target vessel revascularization. The median follow-up duration was 365 days (Q1-Q3: 365-365 days). RESULTS:The OCT guidance group showed a lower incidence of major adverse cardiac events than the angiography guidance group in patients with lesion length ≥32 mm (HR: 0.55; 95% CI: 0.32-0.95; P = 0.031) and RVD <2.8 mm (HR: 0.51; 95% CI: 0.28-0.92; P = 0.026). Across stratified groups based on lesion length and RVD, OCT guidance consistently demonstrated a direction of effect favoring OCT-guided PCI across all lesions (P for interaction = 0.526), with a particularly significant reduction in lesions ≥32 mm with RVD <2.8 mm (HR: 0.46; 95% CI: 0.23-0.94; P = 0.041). CONCLUSIONS:This post hoc analysis of the OCCUPI trial showed that clinical outcomes consistently favored OCT-guided PCI across varying lesion lengths and RVD, with the most pronounced benefit evident in lesions ≥32 mm with RVD <2.8 mm. (Optical CoherenCe Tomography-gUided Coronary Intervention in Patients With Complex lesIons: a Randomized Controlled Trial [OCCUPI Trial]; NCT03625908).

BACKGROUND:Evidence for non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy for older patients with atrial fibrillation (AF) and drug-eluting stents is lacking. OBJECTIVES:We aimed to evaluate the safety and efficacy of NOAC monotherapy in older AF patients with drug-eluting stents. METHODS:This is a secondary analysis of the ADAPT AF-DES randomised trial comparing NOAC monotherapy with combination therapy with NOAC plus clopidogrel in patients with AF and drug-eluting stents. Patients were stratified by age (≥75 years and <75 years). Apixaban or rivaroxaban was used as the NOAC. The primary endpoint was a net adverse clinical event at 1 year after randomisation, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism or major or clinically relevant non-major bleeding defined by the International Society on Thrombosis and Haemostasis criteria. RESULTS:Among 960 patients included in the ADAPT AF-DES trial, 376 (39.2%) patients were aged ≥75 years. In patients aged ≥75 years, the incidence of the primary endpoint was lower in the NOAC monotherapy group (9.8% vs. 22.3%; adjusted hazard ratio, 0.37; 95% confidence interval, 0.21-0.66; P < .001) than in the combination therapy group. In contrast, the incidences did not differ between treatment strategies in patients aged <75 years. The interaction between age groups and strategy groups did not reach statistical significance (P for interaction = .095). The reduction in major or clinically relevant non-major bleeding with NOAC monotherapy was consistent across age groups. In contrast, the benefit of NOAC monotherapy in major adverse cardiac and cerebrovascular events was more pronounced in patients aged ≥75 years, with a statistically significant interaction. CONCLUSIONS:In this post hoc analysis, NOAC monotherapy was associated with a lower risk of net adverse clinical events, specifically within the older age subgroup. Tailored approach regarding age and individual ischaemic risk may be needed.

To evaluate whether combined cilostazol and rosuvastatin therapy improves health-related quality of life, walking performance, and lipid profiles compared with rosuvastatin alone in patients with symptomatic lower extremity peripheral artery disease (PAD). This multicenter, double-blind, randomized placebo-controlled trial enrolled 260 patients with chronic lower extremity PAD (Rutherford category 2 or 3) at 52 sites in Korea. Participants were randomly assigned (1:1) to receive cilostazol 200 mg plus rosuvastatin or a matching placebo plus rosuvastatin for 24 weeks. The primary endpoint was the change in the Korean Peripheral Artery Questionnaire (KPAQ) summary score from baseline to week 24. A total of 257 patients were included in the full analysis set. The combination therapy group showed significantly greater improvement in the KPAQ summary score than in the rosuvastatin monotherapy group (least-squares mean change: 15.4 vs. 10.3 points; between-group difference 5.1 points, 95

BACKGROUND:Ticagrelor monotherapy following abbreviated dual antiplatelet therapy (DAPT) is an emerging strategy for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). However, the timing of aspirin discontinuation has not been directly compared in this setting. AIMS:We aimed to compare the clinical outcomes of aspirin discontinuation within 1 month versus at 3 months after PCI in patients with ACS. METHODS:This post hoc analysis used individual patient-level data from the TICO and T-PASS trials, which exclusively enrolled patients with ACS undergoing PCI. Of 2,953 patients who received ticagrelor monotherapy after abbreviated DAPT, 1,426 discontinued aspirin within 1 month and 1,527 at 3 months. After propensity score matching, 2,248 patients were included in the final analysis. The primary endpoint was a composite of all-cause death, myocardial infarction, stent thrombosis, ischaemia-driven target vessel revascularisation, stroke, and major bleeding at 1 year. RESULTS:The primary endpoint occurred less frequently in the <1-month group than in the 3-month group (3.2% vs 5.6%; hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.37-0.84; p=0.005). Ischaemic event rates were comparable (2.2% vs 2.3%; HR 0.86, 95% CI: 0.55-1.65; p=0.863), whereas major bleeding was significantly lower in the <1-month group (1.1% vs 3.3%; HR 0.32, 95% CI: 0.17-0.61; p<0.001). Landmark analysis showed that event rates diverged primarily within the first 90 days, with no significant heterogeneity between the early and late periods. CONCLUSIONS:Aspirin discontinuation within 1 month followed by ticagrelor monotherapy improved net clinical outcomes compared with 3-month discontinuation, primarily by reducing major bleeding without increasing ischaemic risk. CLINICALTRIALS:gov: NCT02494895 (TICO), NCT03797651 (T-PASS).

BACKGROUND AND AIMS:This study evaluated the incidence, determinants, and clinical impact of stent optimization after optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) for complex lesions. METHODS:From the OCCUPI randomized trial investigating the impact of OCT guidance compared to angiography guidance in complex lesions, patients who underwent OCT-guided PCI with post-stenting OCT evaluations were enrolled and classified into two groups based on whether they met the OCCUPI-OCT criteria: OCT Optimization vs OCT Sub-Optimization. The primary endpoint was the cumulative incidence of cardiac death, myocardial infarction, stent thrombosis, or ischemia-driven target vessel revascularization during one year in the as-treated population. RESULTS:Among the 773 patients who underwent OCT-guided PCI, 549 (71.0%) met the optimization criteria (OCT Optimization), whereas 224 did not (OCT Sub-Optimization). On multivariable analysis, long lesions and small-vessel disease were significant independent predictors of OCT Sub-Optimization. The occurrence of the primary endpoint was significantly lower in the OCT Optimization (2.9%) than in the OCT Sub-Optimization [9.4%, hazard ratio (HR): 0.30, 95% confidence interval (CI): 0.16-0.58, P < .001] or angiography guidance [7.5%, HR: 0.38, 95% CI: 0.22-0.66, P < .001]. Each acceptable component of OCCUPI-OCT criteria assessing stent expansion (minimal stent area, ≥80% mean reference lumen or ≥100% distal reference lumen areas; > 4.5 mm2), apposition (malapposed distance, <400 μm), and absence of major edge dissection, was significantly associated with favourable outcomes (all P < .001). CONCLUSIONS:The current study identifies long lesions or small-vessel disease as the determinants of stent optimization following OCT guidance, with the achievement of stent optimization significantly associated with improved clinical outcomes. Stent expansion, apposition, and edge dissection, the three key components of the OCCUPI-OCT criteria, were highly predictive of favourable clinical outcomes.

BACKGROUND:Adequate distal perfusion assessment is crucial for managing chronic limb-threatening ischemia (CLTI). Skin perfusion pressure (SPP) and transcutaneous oxygen pressure (TcPO2) are commonly used to evaluate perfusion and predict wound healing. The main objective of this study was to compare the effectiveness of SPP and TcPO2 in predicting early wound healing following endovascular therapy (EVT) for CLTI. METHODS:We retrospectively reviewed 99 limbs from 87 patients with Rutherford category 5 or 6 CLTI enrolled in the K-VIS ELLA registry (ClinicalTrials.gov Identifier: NCT02748226). SPP and TcPO2 were measured before and within 48 hours after EVT. Clinical outcomes included early wound healing (defined as complete epithelialization without major amputation within 3 months), major amputation, repeat revascularization, major adverse limb events (MALE), and all-cause death. RESULTS:A high post-EVT SPP (⩾ 48 mmHg) significantly predicted early wound healing and was associated with a higher proportion of wound healing and a lower risk of repeat revascularization at 6 months. TcPO2 did not significantly predict early wound healing; however, a high post-EVT TcPO2 (⩾ 27 mmHg) correlated with lower proportions of repeat revascularization and MALE at 6 months. Neither SPP nor TcPO2 was associated with mortality or major amputation. CONCLUSION:High SPP within 48 hours post-EVT was a significant predictor of early wound healing in CLTI. Although TcPO2 was not predictive of early wound healing, it was linked to other favorable limb outcomes. Further studies are required to validate our findings and define the complementary roles of SPP and TcPO2 in managing CLTI.

BACKGROUND:The effect of clopidogrel monotherapy as compared with extended dual antiplatelet therapy (DAPT) with clopidogrel and aspirin beyond 12 months after implantation of a drug-eluting stent remains uncertain in patients at high risk for recurrent ischemic events. METHODS:In this open-label noninferiority trial conducted in South Korea, we enrolled patients with high-risk clinical or lesion characteristics in whom a drug-eluting stent had been implanted 12 months earlier and randomly assigned them, in a 1:1 ratio, to receive clopidogrel monotherapy or extended DAPT (clopidogrel plus aspirin). The primary end point was net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 24 months (noninferiority margin, 2.3 percentage points). Key secondary ischemic and bleeding end points were tested in a prespecified hierarchical order. RESULTS:Of the 3203 patients who underwent randomization, 1601 were assigned to receive clopidogrel monotherapy and 1602 to receive extended DAPT. Over the course of 24 months, a primary end-point event occurred in 80 patients (5.0%) in the monotherapy group and in 81 (5.1%) in the DAPT group (risk difference, -0.1 percentage points; 90% confidence interval [CI], -1.3 to 1.2; P = 0.001 for noninferiority). Death from any cause, myocardial infarction, stent thrombosis, or stroke (the key secondary ischemic end point) occurred in 60 patients (3.7%) in the monotherapy group and in 26 (1.6%) in the DAPT group (hazard ratio, 2.33; 95% CI, 1.47 to 3.69; P<0.001). BARC type 2, 3, or 5 bleeding (the key secondary bleeding end point) occurred in 28 patients (1.8%) in the monotherapy group and in 65 (4.1%) in the DAPT group (hazard ratio, 0.43; 95% CI, 0.27 to 0.67; P<0.001). The incidence of serious adverse events was similar in the two groups. CONCLUSIONS:Among patients at high risk for ischemic events 12 months after drug-eluting stent implantation, clopidogrel monotherapy was noninferior to extended DAPT with respect to net adverse clinical events at 24 months. (Funded by Chong Kun Dang and Samjin; A-CLOSE ClinicalTrials.gov number, NCT03947229.).

BACKGROUND AND OBJECTIVES:In South Korea and other countries operating national health insurance, claims data are used to estimate the burden of acute myocardial infarction (AMI) and stroke. However, most previous studies relied on diagnostic claim codes and did not distinguish first-ever from recurrent events. To estimate nationwide trends in the incidence and fatality of AMI and stroke using validated claims-based algorithms that distinguish first-ever from recurrent events. METHODS:We analyzed National Health Insurance Service (NHIS) claims data covering the entire Korean population from 2002 to 2023. The period from 2002-2010 served as a washout period, and annual incidence and case-fatality rates were estimated for 2011-2023. AMI (ICD-10: I21-I23) and stroke (ICD-10: I60-I61, I63-I64) events were identified from hospitalization episodes using diagnostic, procedure, imaging, and mortality codes. Crude and age-standardized rates were calculated. RESULTS:Between 2011 and 2023, AMI events increased from 22,395 to 34,768, including 1,472 to 3,373 recurrent cases. Stroke events rose from 99,837 to 113,098, including 16,925 to 22,813 recurrent cases. Crude incidence increased for AMI (44.7 to 68.0 per 100,000 person-years) and stroke (199.2 to 221.1), whereas age-standardized incidence increased slightly for AMI (35.7 to 37.1) but declined markedly for stroke (158.3 to 113.2). AMI fatality rates remained stable, whereas stroke fatality rates declined initially but rose modestly in recent years. CONCLUSIONS:By linking NHIS claims with mortality statistics and applying validated algorithms, this study demonstrates that reliable national monitoring of AMI and stroke incidence and fatality is feasible without extensive hospital-based registries or active surveillance systems.

BACKGROUND AND OBJECTIVES:Coronary chronic total occlusion (CTO) is among the most challenging forms of coronary artery disease, yet large-scale real-world data remain limited. We aimed to describe contemporary CTO clinical practice and outcomes in South Korea. METHODS:The Korean Chronic Total Occlusion (K-CTO) registry 2.0 is a nationwide retrospective registry including patients diagnosed with CTO between 2003 and 2023 at 34 centers performing percutaneous coronary intervention (PCI), irrespective of CTO-PCI performance. Demographic, clinical, procedural, and outcome data were analyzed. RESULTS:Of 9,316 patients with CTO, 7,267 (78.0%) underwent PCI. The overall procedural success rate was 82.2%. The antegrade approach was used in 87.5% of cases and the retrograde in 12.5%, with procedural success rates of 82.8% and 78.5%, respectively. Intravascular ultrasonography was employed in 37.3%, and drug-eluting stents were implanted in 76.8%. Predictors of PCI attempts included younger age, prior PCI, and stable angina, whereas diabetes mellitus (DM), chronic kidney disease (CKD), prior CABG, and higher Japanese CTO scores were associated with less frequent PCI attempts. In-hospital all-cause mortality was 2.3% and periprocedural myocardial infarction (MI) 4.4%. At a median follow-up of 651 days, 5-year cumulative incidences of major adverse cardiac and cerebrovascular events, major adverse cardiac events, net adverse clinical events, and all-cause mortality were 30.4%, 28.5%, 30.9%, and 14.5%, respectively. CONCLUSIONS:In routine practice across South Korea, most patients with CTO underwent PCI with high success. These descriptive findings should not be interpreted as evidence of improved long-term outcomes. Broader adoption of advanced techniques and device accessibility may further improve results in complex CTO lesions.

BACKGROUND:Although shortened dual antiplatelet therapy (DAPT) strategies have demonstrated favorable outcomes in the general percutaneous coronary intervention (PCI) population, patients with advanced chronic kidney disease (CKD) have been underrepresented in randomized clinical trials. The optimal duration of DAPT after PCI remains uncertain in patients with CKD, who are at increased risk for both ischemic and bleeding events. METHODS:The ADAPT-CKD trial is an investigator-initiated, multicenter, open-label, randomized, superiority study designed to compare an abbreviated vs a standard DAPT strategy in patients with advanced CKD undergoing PCI with contemporary drug-eluting stents. A total of 900 patients with an estimated glomerular filtration rate <45 mL/min/1.73 m² will be randomly assigned in a 1:1 ratio to abbreviated DAPT (<3 months of DAPT after PCI) or standard DAPT (≥6 months). The primary endpoint is net adverse clinical events at 1 year, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, or major bleeding according to the Bleeding Academic Research Consortium criteria. The primary hypothesis is that abbreviated DAPT is superior to standard DAPT in reducing net adverse clinical events at 1 year after randomization. CONCLUSIONS:The ADAPT-CKD trial will provide randomized evidence on the efficacy and safety of an abbreviated DAPT strategy compared with a standard DAPT strategy in patients with advanced CKD undergoing PCI. The results are expected to inform clinical decision-making regarding optimal antiplatelet therapy in this high-risk population. CLINICAL TRIAL REGISTRATION:https://www. CLINICALTRIALS:gov. Unique identifier: NCT04708587.

Purpose: Drug-coated balloons (DCBs) have demonstrated favorable outcomes in the treatment of femoropopliteal artery (FPA) disease. A variety of DCBs are currently available, with differing doses of antiproliferative agents and types of excipients. The objective of this study was to compare the efficacy and safety of high-dose versus low-dose paclitaxel DCBs for the treatment of FPA disease. Materials and Methods: We analyzed data from the multicenter the Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS ELLA) registry, focusing on patients treated with a high-dose paclitaxel DCB (IN.PACTTM) or low-dose paclitaxel DCB (LutonixTM or RangerTM) for native vessel FPA disease. We used inverse probability of treatment weighting to adjust for confounding factors and conducted subgroup analyses based on lesion characteristics. Results: Among 820 target limbs, 626 were treated with a high-dose paclitaxel DCB, and 194 were treated with a low-dose paclitaxel DCB. At 12 months, there were no significant differences in rates of freedom from clinically driven target lesion revascularization (TLR; 91.7% vs. 89.4%, log-rank p=0.35), major adverse limb event (MALE; 91.4% vs. 89.0%, log-rank p=0.31), or all-cause mortality (93.1% vs. 93.8%, log-rank p=0.79) between high-dose and low-dose groups. On multivariable analysis, the presence of chronic heart failure and chronic kidney disease were the only independent predictors of clinically driven TLR after DCB treatment. Conclusion: In this multicenter cohort study of patients with complex FPA disease, there were no significant differences between high-dose DCB and low-dose DCB with respect to freedom from clinically driven TLR, MALE, or all-cause mortality at 12-month follow-up. Trial registration: ClinicalTrials.gov Identifier : NCT02748226

PURPOSE:We aimed to compare the visit-to-visit variability in low-density lipoprotein cholesterol (LDL-C) according to different lipid-lowering strategies and evaluate its prognostic implications using data from previous trials. MATERIALS AND METHODS:We analyzed two randomized clinical trials: the RACING trial and the LODESTAR trial. LDL-C variability was evaluated using standard deviation (SD), coefficient of variation, and variation independent of mean. The primary endpoint was a composite of death, myocardial infarction, stroke, or coronary revascularization. RESULTS:Among the 6800 patients included, when compared with patients randomized to high-intensity statins, LDL-C variability was similar in the group randomized to moderate-intensity statin plus ezetimibe combination, but it was higher in those randomized to treat-to-target strategy. The variability in LDL-C (by SD) was a predictor of primary endpoint even after adjustment for lipid-lowering strategy and mean LDL-C (hazard ratio 1.024; 95% confidence interval 1.014 to 1.035; p<0.001). Every 1-SD increase in LDL-C variability (SD) was also independently associated with higher risk of myocardial infarction by 2.1%, stroke by 3.5%, and coronary revascularization by 2.7%. CONCLUSION:Compared to high-intensity statin therapy, LDL-C variability was not increased with the moderate-intensity statin plus ezetimibe combination therapy; however, it was increased in the treat-to-target strategy. Even among those treated with moderate- or high-intensity statins or statins with a target LDL-C levels of 50-70 mg/dL, increased LDL-C variability was associated with higher risk of adverse cardiovascular outcomes.