Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention for acute myocardial infarction with cardiogenic shock.

The benefits of intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) in the clinical context of cardiogenic shock (CS) complicating acute myocardial infarction are lacking. We aimed to investigate the impact of IVUS-guided PCI in patients with AMI and CS. From the pooled data based on a series of Korean AMI registries during 2011-2020, we identified 1418 consecutive patients who underwent PCI with second generation drug-eluting stent (DES) for AMI and CS. The primary endpoint was the 1-year rate of target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction, and ischemic-driven target lesion revascularization. In total, 294 (20.7%) and 1124 (79.3%) underwent IVUS-guided and angiography-guided PCI with second generation DES implantation, respectively. The 1-year TLF was not significantly different between groups after IPTW analysis (hazard ratio 0.93, 95% confidence interval 0.65-1.34, p = 0.70). Additionally, the adjusted landmark analysis for TLF at 30 days and between 30 days and 1 year after PCI demonstrated no significant difference between the groups. In conclusion, in patients with AMI and CS who underwent PCI with second-generation DES, IVUS-guided PCI did not improve the 1-year TLF compared with angiography-guided PCI.Registration: URL:  http://cris.nih.go.kr . KCT0000863 and KCT0008355.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results.

BACKGROUND AND OBJECTIVES: The popliteal artery is generally regarded as a "no-stent zone". Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease. METHODS: This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)-free rate. RESULTS: The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency. CONCLUSIONS: DCB treatment yielded favorable 12-month clinical primary patency and TLR-free survival outcomes in patients with popliteal artery disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02698345.

IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.

Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor-infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD-1-negative tumor non-responsive bystander T cells. However, they are non-exhausted and central memory-phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen-specific TCEs to acquire tumoricidal activity. Single-cell transcriptome analysis reveals that rhIL-7-hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.

Understanding the pharmacokinetic journey of Fc-fusion protein, rhIL-7-hyFc using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA.

Antibody-based therapeutics (ABTs), including monoclonal/polyclonal antibodies and fragment crystallizable region (Fc)-fusion proteins, are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS). Totally, four rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14C-rhIL-7-hyFc, which was prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. The TRA concentrations in organs were determined by AMS. Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. The rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed an elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc's affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method. Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offers valuable insights for the development and optimization of ABT.

Predictive value of plaque characteristics for identification of lesions causing ischemia.

BACKGROUND: Functional assessment using fractional flow reserve (FFR) and anatomical assessment using optical coherence tomography (OCT) are used in clinical practice for patients with intermediate coronary stenosis. Moreover, coronary computed tomography angiography (CTA) is a common noninvasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. This study aimed to investigate the association between FFR and plaque characteristics assessed using coronary CTA and OCT for intermediate coronary stenosis. METHODS: Based on a prospective multicenter registry, 159 patients having 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography, and both FFR measurements and OCT examinations were performed during angiography. A stenotic lesion identified with FFR ≤0.80 was deemed diagnostic of an ischemia-causing lesion. The predictive value of plaque characteristics assessed using coronary CTA and OCT for identifying lesions causing ischemia was analyzed. RESULTS: Stenosis severity and plaque characteristics on coronary CTA and OCT differed between lesions that caused ischemia and those that did not. In multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]=2.78; P=0.038), thrombus (OR=5.13; P=0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors of ischemic lesions. Increasing the number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. CONCLUSIONS: Comprehensive anatomical evaluation of coronary stenosis may provide additional supportive information for predicting the lesions causing ischemia.

Harnessing the Power of IL-7 to Boost T Cell Immunity in Experimental and Clinical Immunotherapies.

The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

rhIL-7-hyFc and hIL-2/TCB2c combination promotes an immune-stimulatory tumor microenvironment that improves antitumor efficacy of checkpoint inhibitors.

BACKGROUND: Recombinant human interleukin (rhIL)-7-hyFc (efineptakin alfa; NT-I7) is a potent T-cell amplifier, with two IL-7 molecules fused to IgD/IgG4 elements. rhIL-7-hyFc promotes extensive infiltration of CD8+ T cells into the tumor, concurrently increasing the numbers of intratumoral PD-1+CD8+ T cells. The hIL-2/TCB2 complex (SLC-3010) inhibits tumor growth by preferential activation of CD122 (IL-2Rß)high CD8+ T cells and natural killer cells, over regulatory T cells (Tregs). We investigated the underlying mechanisms of rhIL-7-hyFc and hIL-2/TCB2c antitumor activity and the potential synergistic efficacy, specifically focusing on tumor-specific CD8+ cells within the tumor and the tumor-draining lymph nodes (tdLN). METHODS: MC38 and CT26 tumor-bearing mice were administered with 10 mg/kg rhIL-7-hyFc intramuscularly and 0.9 mg/kg hIL-2/TCB2c intravenously. Anti-PD-1 monoclonal antibody was administered intraperitoneally three times at 3-day intervals at a dose of 5 mg/kg. Tumor volume was measured to assess efficacy. To compare the composition of immune cells between each monotherapy and the combination therapy, we analyzed tumors and tdLNs by flow cytometry. RESULTS: Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME). The TME is characterized by an increased infiltration of tumor-specific CD8+ T cells, and a decreased frequency of CD39highTIM-3+ Treg cells. Most importantly, rhIL-7-hyFc increases infiltration of a CD62L+Ly108+ early progenitor population of exhausted CD8+ T cells (TPEX), which may retain long-term proliferation capacity and replenish functional effector CD8+ T cells. hIL-2/TCB2c induces differentiation of CD62L+Ly108+ TPEX rapidly into CD101+ terminally differentiated subsets (terminally exhausted T cell (TEX term)). Our study also demonstrates that rhIL-7-hyFc significantly enhances the proliferation rate of TPEX in the tdLNs, positively correlating with their abundance within the tumor. Moreover, rhIL-7-hyFc and hIL-2/TCB2c can overcome the limited therapeutic effectiveness of PD-1 blockade, culminating in the complete regression of tumors. CONCLUSIONS: rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+ T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.

Long-Term Outcomes of Endovascular Repair Within and Outside the Instructions for Use in Korean Patients With Abdominal Aortic Aneurysm.

OBJECTIVE: Endovascular aneurysm repair (EVAR) has been used worldwide to treat abdominal aortic aneurysms (AAAs). Outcomes after EVAR within and outside the instruction for use (IFU) remain controversial. We analyzed long-term outcomes of EVAR within-the-IFU compared with that outside-the-IFU and baseline clinical/anatomical characteristics that influence outcomes of EVAR. METHODS: The study included 546 patients who underwent EVAR for infrarenal AAA from 1997 to 2021 at 2 Korean medical centers. The primary endpoint was graft-related adverse events (GRAEs), including type 1 or 3 endoleak, reintervention (included open conversion), aneurysm sac enlargement, aneurysm-related mortality (ARM), rupture, stent-graft migration, and stent thrombotic occlusion. RESULTS: The patients who underwent EVAR outside the IFU were 287 (52.6%). A neck angle of >60° was most common outside the IFU criteria (n=146, 50.9%). This study revealed that patients outside the IFU had a higher rate of GRAEs compared with patients within the IFU (hazard ratio [HR]: 1.879; 95% confidence interval [CI]: 1.045-2.386). A neck angle of >60° was a significant risk factor for GRAEs (adjusted HR: 2.229; 95% CI: 1.418-3.503), type 1 or 3 endoleak (adjusted HR: 2.640; 95% CI: 1.343-5.189), and reintervention (adjusted HR: 1.891; 95% CI: 1.055-3.388). CONCLUSIONS: Our study revealed EVAR with outside the IFU was associated with increased GRAEs, mainly attributed to endoleak and ARM, compared with EVAR with within the IFU. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak, and reintervention. CLINICAL IMPACT: Our study revealed endovascular aneurysm repair (EVAR) with outside-the-instruction for use (IFU) was associated with increased graft-related adverse events (GRAEs) compared with EVAR with within-the-IFU. In the low-risk population, the incidence of GRAEs and Aneurysm related mortality were higher in the outside-the-IFU group rather than within-the-IFU group. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak and reintervention.

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome and atherosclerotic cardiovascular disease: A post-hoc analysis of the RACING trial.

AIM: This study evaluated the safety and efficacy of a moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease. MATERIALS AND METHODS: In this post-hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high-density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high-intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72-1.32; p = .868). Lower rates of intolerance-related drug discontinuation or dose reduction (3.9% vs. 8.0%; p < .001) and lower low-density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p < .001) were observed with ezetimibe combination therapy versus high-intensity statin monotherapy. Furthermore, the rate of new-onset diabetes was 18.5% and 19.1% in each group (p = .822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population. CONCLUSIONS: In patients with MetS and atherosclerotic cardiovascular disease, a moderate-intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high-intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low-density lipoprotein cholesterol levels, but there was no apparent between-group difference in new-onset diabetes.

Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial.

BACKGROUND: Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome. METHODS: In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point. RESULTS: Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment-elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12-25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37-0.80]; P<0.001 for noninferiority; P=0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20-0.61]; P<0.001). CONCLUSIONS: This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non-high-risk patients, should be considered in interpreting the trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651.

Comparison of Intracardiac Echocardiography Versus Transesophageal Echocardiography for Guidance During Transcatheter Aortic Valve Replacement.

BACKGROUND AND OBJECTIVES: Evidence regarding the efficacy and safety of intracardiac echocardiography (ICE) for guidance during transcatheter aortic valve replacement (TAVR) is limited. This study aimed to compare the clinical efficacy and safety of ICE versus transesophageal echocardiography (TEE) for guiding TAVR. METHODS: This prospective cohort study included patients who underwent TAVR from August 18, 2015, to June 31, 2021. Eligible patients were stratified by echocardiographic modality (ICE or TEE) and anesthesia mode (monitored anesthesia care [MAC] or general anesthesia [GA]). Primary outcome was the 1-year composite of all-cause mortality, rehospitalization for cardiovascular cause, or stroke, according to the Valve Academic Research Consortium-3 (VARC-3) definition. Propensity score matching was performed, and study outcomes were analyzed for the matched cohorts. RESULTS: Of the 359 eligible patients, 120 patients were matched for the ICE-MAC and TEE-GA groups, respectively. The incidence of primary outcome was similar between matched groups (18.3% vs. 20.0%; adjusted hazard ratio, 0.94; 95% confidence interval [CI], 0.53-1.68; p=0.843). ICE-MAC and TEE-GA also had similar incidences of moderate-to-severe paravalvular regurgitation (PVR) (4.2% vs. 5.0%; adjusted odds ratio, 0.83; 95% CI, 0.23-2.82; p=0.758), new permanent pacemaker implantation, and VARC-3 types 2-4 bleeding. CONCLUSIONS: ICE was comparable to TEE for guidance during TAVR for the composite clinical efficacy outcome, with similar incidences of moderate-to-severe PVR, new permanent pacemaker implantation, and major bleeding. These results suggest that ICE could be a safe and effective alternative echocardiographic modality to TEE for guiding TAVR.

Optical coherence tomography-guided versus intravascular ultrasound-guided percutaneous coronary intervention in patients with acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) yields clinical outcomes comparable to intravascular ultrasound (IVUS)-guided PCI in patients with stable ischemic heart disease. However, there is a scarcity of data comparing the clinical outcomes of OCT-guided and IVUS-guided PCI in the setting of acute myocardial infarction (AMI). We sought to compare the clinical outcomes of OCT-guided vs IVUS-guided PCI for patients with AMI in the era of second-generation drug-eluting stent (DES). METHODS: We identified 5260 consecutive patients who underwent PCI with a second-generation DES for AMI under IVUS or OCT guidance from pooled data derived from a series of Korean AMI registries between 2011 and 2020. The primary endpoint was the 1-year rate of target lesion failure, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. RESULTS: A total of 535 (10.2%) and 4725 (89.8%) patients were treated under OCT and IVUS guidance, respectively. The 1-year target lesion failure rates were comparable between the OCT and IVUS groups before and after propensity score matching (hazard ratio, 0.92; 95%CI, 0.42-2.05, P=.84). The OCT utilization rate did not exceed 5% of total patients treated with second-generation DES implantation during the study period. The primary factors for the selection of OCT over IVUS were the absence of chronic kidney disease, non-left main vessel disease, single-vessel disease, stent diameter <3mm, and stent length ≤ 25mm. CONCLUSIONS: OCT-guided PCI in patients with AMI treated with a second-generation DES provided comparable clinical outcomes for 1-year target lesion failure compared with IVUS-guided PCI.

Combination therapy with moderate-intensity atorvastatin and ezetimibe versus high-intensity atorvastatin monotherapy in patients treated with percutaneous coronary intervention in practice: assessing RACING generalizability.

AIMS: Using rosuvastatin, the RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial showed the beneficial effects of combining moderate-intensity statin with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease. This study investigated whether the beneficial effects of combination lipid-lowering therapy extend to patients treated with atorvastatin, not rosuvastatin, in daily clinical practice. METHODS AND RESULTS: Using stabilized inverse probability of treatment weighting, a total of 31 993 patients who were prescribed atorvastatin after drug-eluting stent (DES) implantation were identified from a nationwide cohort database: 6 215 patients with atorvastatin 20 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 25 778 patients with atorvastatin 40-80 mg monotherapy. The primary endpoint was the 3-year composite of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or non-fatal stroke in accordance with the RACING trial design. Combination lipid-lowering therapy was associated with a lower incidence of the primary endpoint (12.9% vs. 15.1% in high-intensity atorvastatin monotherapy; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.74-0.88, p < 0.001). Compared with high-intensity atorvastatin monotherapy, combination lipid-lowering therapy was also significantly associated with lower rates of statin discontinuation (10.0% vs. 8.4%, HR 0.81, 95% CI 0.73-0.90, p < 0.001) and new-onset diabetes requiring medication (8.8% vs. 7.0%, HR 0.80, 95% CI 0.70-0.92, p = 0.002). CONCLUSIONS: In clinical practice, a combined lipid-lowering approach utilizing ezetimibe and moderate-intensity atorvastatin was correlated with favorable clinical outcomes, drug compliance, and a reduced incidence of new-onset diabetes requiring medications in patients treated with DES implantation. Trial registration: ClinicalTrial.gov (NCT04715594).

Association Between Body Mass Index and Clinical Outcomes According to Diabetes in Patients Who Underwent Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: We evaluated the effect of diabetes on the relationship between body mass index (BMI) and clinical outcomes in patients following percutaneous coronary intervention (PCI) with drug-eluting stent implantation. METHODS: A total of 6,688 patients who underwent PCI were selected from five different registries led by Korean Multicenter Angioplasty Team. They were categorized according to their BMI into the following groups: underweight (<18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight to obese (≥25.0 kg/m²). Major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of death, nonfatal myocardial infarction, stroke, and target-vessel revascularization, were compared according to the BMI categories (underweight, normal and overweight to obese group) and diabetic status. All subjects completed 1-year follow-up. RESULTS: Among the 6,688 patients, 2,561 (38%) had diabetes. The underweight group compared to normal weight group had higher 1-year MACCE rate in both non-diabetic (adjusted hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.04-4.84; p=0.039) and diabetic patients (adjusted HR, 2.86; 95% CI, 1.61-5.07; p<0.001). The overweight to obese group had a lower MACCE rate than the normal weight group in diabetic patients (adjusted HR, 0.67 [0.49-0.93]) but not in non-diabetic patients (adjusted HR, 1.06 [0.77-1.46]), with a significant interaction (p-interaction=0.025). CONCLUSIONS: Between the underweight and normal weight groups, the association between the BMI and clinical outcomes was consistent regardless of the presence of diabetes. However, better outcomes in overweight to obese over normal weight were observed only in diabetic patients. These results suggest that the association between BMI and clinical outcomes may differ according to the diabetic status.

Moderate-intensity statin plus ezetimibe vs high-intensity statin according to baseline LDL-C in the treatment of atherosclerotic cardiovascular disease: A post-hoc analysis of the RACING randomized trial.

BACKGROUND AND AIMS: Whether the effect of a combination strategy rather than increasing doses of one drug to lower low-density lipoprotein cholesterol (LDL-C) levels is consistent across baseline LDL-C levels remains uncertain. METHODS: In the RACING trial, which showed a non-inferiority of moderate-intensity statin with ezetimibe (rosuvastatin 10 mg with ezetimibe 10 mg) to high-intensity statin (rosuvastatin 20 mg) for the primary outcome (3-year composite of cardiovascular death, major cardiovascular event, or stroke), the heterogeneity in treatment effect according to baseline LDL-C levels was assessed for the primary and secondary outcomes (clinical efficacy and safety). RESULTS: Of 3780 participants, 2817 participants (74.5%) had LDL-C <100 mg/dL, and 963 participants (25.5%) had LDL-C ≥100 mg/dL. The treatment effect of combination therapy versus high-intensity statin monotherapy was similar among the lower LDL-C subset (8.8% vs. 10.2%; hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.67 to 1.08, p = 0.19) and the higher LDL-C subset (10.8% vs. 9.6 %; HR 1.14, 95% CI 0.76 to 1.7, p = 0.53) without a significant interaction (interaction p = 0.22). Of the secondary outcomes, the 1-, 2-, and 3-year achievement of LDL-C <70 mg/dL was greater in the combination therapy group regardless of baseline LDL-C levels. CONCLUSIONS: Among ASCVD patients, there was no heterogeneity in the effect of moderate-intensity statin plus ezetimibe combination therapy in the higher and lower baseline LDL-C levels for the 3-year composite of cardiovascular outcomes.

Effect of moderate-intensity statin with ezetimibe combination vs. high-intensity statin therapy according to sex in patients with atherosclerosis.

We aimed to evaluate sex differences in the effects of moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg plus ezetimibe) versus high-intensity statin (rosuvastatin 20 mg) monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). This was a sex-specific subgroup analysis of the RACING trial that evaluated the interaction between sex and treatment strategies for the primary outcome (composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years). Of 3780 patients in the RACING trial, 954 (25.2%) were women. Regardless of sex, the effect of moderate-intensity statin with ezetimibe combination therapy on primary outcome compared with high-intensity statin monotherapy was similar (hazard ratio [HR] 0.98 [0.63-1.52] in women; HR 0.90 [0.71-1.14] in men). The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P < 0.001). LDL cholesterol levels of < 70 mg/dL at 1, 2, and 3 years were more frequently achieved in the ezetimibe combination group than in the high-intensity statin monotherapy group (all P < 0.001) in both sexes. There were no significant interactions between sex and treatment groups regarding the primary outcome, discontinuation, or dose reduction of study drugs, or the proportion of achievement of LDL cholesterol levels < 70 mg/dL. The effect of ezetimibe combination therapy for the 3-year composite outcomes was not different in both men and women. The benefits of ezetimibe combination therapy on LDL cholesterol lowering and drug tolerance were similarly observed regardless of sex.Trial registration: https://clinicaltrials.gov ; Unique identifier: NCT03044665.

Association of Prophylactic Distal Perfusion Cannulation With Mortality in Patients Receiving Venoarterial Extracorporeal Membrane Oxygenation.

Prophylactic distal perfusion cannulation (PDPC) is protectively associated with limb ischemia in patients with cardiogenic shock (CS) receiving femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, evidence supporting its benefits beyond limb ischemia reduction is scarce. We aimed to investigate whether PDPC, compared with no-PDPC, is associated with a lower risk of mortality in patients receiving VA-ECMO. From a multicenter registry, we identified 479 patients who underwent VA-ECMO support for refractory CS. The association of PDPC with 30-day mortality was assessed using multiple methods, including instrumental variable analysis, overlap weighting, and propensity score matching. Of the 479 patients, 154 (32.2%) received PDPC. The 30-day mortality rate was 33.1% in the PDPC group and 53.2% in the no-PDPC group. The instrumental variable analysis showed a protective association of PDPC with 30-day mortality (absolute risk difference -16.7%, 95% confidence interval -31.3% to -2.1%; relative risk 0.68, 95% confidence interval 0.40 to 0.96). The findings were consistent in the overlap-weighted analysis (hazard ratio 0.68, 95% confidence interval 0.48 to 0.98) and in the propensity score-matched analysis (hazard ratio 0.67, 95% confidence interval 0.45 to 1.00). There were no significant differences in safety outcomes, including stroke, ECMO site bleeding, gastrointestinal bleeding, and sepsis, between PDPC and no-PDPC. In conclusion, PDPC was associated with a lower risk of mortality at 30 days in patients with CS receiving VA-ECMO. The efficacy and safety of PDPC merit evaluation in future randomized studies. Clinical trial registration: ClinicalTrials.gov; NCT02985008.

Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial.

OBJECTIVE: To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease. DESIGN: Randomised, open label, multicentre trial. SETTING: 12 hospitals in South Korea, September 2016 to November 2019. PARTICIPANTS: 4400 adults (age ≥19 years) with coronary artery disease. INTERVENTIONS: Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation. MAIN OUTCOME MEASURES: The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities. RESULTS: 4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% v 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% v 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups. CONCLUSIONS: In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT02579499.