Safety and Efficacy of Ticagrelor Monotherapy in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: An Individual Patient Data Meta-Analysis of TWILIGHT and TICO Randomized Trials.

BACKGROUND: Dual antiplatelet therapy with a potent P2Y12 inhibitor coupled with aspirin for 1 year is the recommended treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). As an alternative, monotherapy with a P2Y12 inhibitor after a short period of dual antiplatelet therapy has emerged as a bleeding reduction strategy. METHODS: We pooled individual patient data from randomized trials that included patients with ACS undergoing PCI treated with an initial 3-month course of dual antiplatelet therapy followed by ticagrelor monotherapy versus continued ticagrelor plus aspirin. Patients sustaining a major ischemic or bleeding event in the first 3 months after PCI were excluded from analysis. The primary outcome was Bleeding Academic Research Consortium type 3 or 5 bleeding occurring between 3 and 12 months after index PCI. The key secondary end point was the composite of death, myocardial infarction, or stroke. Hazard ratios and 95% CIs were generated using Cox regression with a one-stage approach in the intention-to-treat population. RESULTS: The pooled cohort (n=7529) had a mean age of 62.8 years, 23.2% were female, and 55% presented with biomarker-positive ACS. Between 3 and 12 months, ticagrelor monotherapy significantly reduced Bleeding Academic Research Consortium 3 or 5 bleeding compared with ticagrelor plus aspirin (0.8% versus 2.1%; hazard ratio, 0.37 [95% CI, 0.24-0.56]; P<0.001). Rates of all-cause death, myocardial infarction, or stroke were not significantly different between groups (2.4% versus 2.7%; hazard ratio, 0.91 [95% CI, 0.68-1.21]; P=0.515). Findings were unchanged among patients presenting with biomarker-positive ACS. CONCLUSIONS: Among patients with ACS undergoing PCI who have completed a 3-month course of dual antiplatelet therapy, discontinuation of aspirin followed by ticagrelor monotherapy significantly reduced major bleeding without incremental ischemic risk compared with ticagrelor plus aspirin. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023449646.

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.

Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial.

BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.

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).

Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

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.

Treat-to-target or high-intensity statin treatment in older adults with coronary artery disease: a post hoc analysis of the LODESTAR trial.

BACKGROUND: The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). METHODS: In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. RESULTS: Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). CONCLUSIONS: High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579499.

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial.

AIMS: This study evaluated the effect of moderate-intensity statin with ezetimibe combination therapy vs. high-intensity statin monotherapy among patients with diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: This was a pre-specified, stratified subgroup analysis of the DM cohort in the RACING trial. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. Among total patients, 1398 (37.0%) had DM at baseline. The incidence of the primary outcome was 10.0% and 11.3% among patients with DM randomized to ezetimibe combination therapy vs. high-intensity statin monotherapy (hazard ratio: 0.89; 95% confidence interval: 0.64-1.22; P = 0.460). Intolerance-related discontinuation or dose reduction of the study drug was observed in 5.2% and 8.7% of patients in each group, respectively (P = 0.014). LDL cholesterol levels <70 mg/dL at 1, 2, and 3 years were observed in 81.0%, 83.1%, and 79.9% of patients in the ezetimibe combination therapy group, and 64.1%, 70.2%, and 66.8% of patients in the high-intensity statin monotherapy group (all P < 0.001). In the total population, no significant interactions were found between DM status and therapy regarding primary outcome, intolerance-related discontinuation or dose reduction, and the proportion of patients with LDL cholesterol levels <70 mg/dL. CONCLUSION: Ezetimibe combination therapy effects observed in the RACING trial population are preserved among patients with DM. This study supports moderate-intensity statin with ezetimibe combination therapy as a suitable alternative to high-intensity statins if the latter cannot be tolerated, or further reduction in LDL cholesterol is required among patients with DM and ASCVD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier:NCT03044665.

Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial.

BACKGROUND: Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed. METHODS: In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete. FINDINGS: Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001). INTERPRETATION: Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction. FUNDING: Hanmi Pharmaceutical.

Impact of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction and Chronic Kidney Disease.

BACKGROUND: In the setting of acute myocardial infarction (AMI), there are no data regarding the benefits of intravascular ultrasound (IVUS) for chronic kidney disease (CKD) patients.Methods and Results: This study used data from the Korea Acute Myocardial Infarction Registry, a large, multicenter prospective cohort. We evaluated 1,759 patients with AMI and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and patients were classified into 2 groups: with and without IVUS. The primary outcome was target lesion failure (TLF) at 3 years. The hazard ratio (HR) of TLF according to eGFR was also analyzed. A total of 1,759 patients with AMI and CKD who underwent IVUS-guided PCI (19.2%) had a significantly lower risk of TLF at 3 years (8.9% vs. 15.3%; HR 0.55; 95% confidence interval [CI]: 0.38 to 0.81; P=0.002) than those who underwent angiography-guided PCI, regardless of their eGFR and the presence of end-stage renal disease (ESRD). The results were consistent after confounder adjustment and inversed probability weighting. CONCLUSIONS: In patients with CKD and AMI who underwent PCI with 2nd-generation DES implantation, the use of IVUS guidance was associated with a significant reduction in 3-year TLF and showed consistently favorable outcomes regardless of eGFR and ESRD.

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial.

Importance: In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. Objective: To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. Design, Setting, and Participants: A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022). Interventions: Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Main Outcomes and Measures: Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Results: Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority). Conclusions and Relevance: Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02579499.

Two-year outcomes between ST-elevation and non-ST-elevation myocardial infarction in patients with chronic kidney disease undergoing newer-generation drug-eluting stent implantation.

BACKGROUND: We evaluated the 2-year clinical outcomes of ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) in patients with chronic kidney disease (CKD) who received newer-generation drug-eluting stents (DES). METHODS: Overall, 18,875 acute myocardial infarction patients were divided into two groups: CKD (STEMI, n = 1707; NSTEMI, n = 1648) and non-CKD (STEMI, n = 8660; NSTEMI, n = 6860). The occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), any repeat coronary revascularization, and definite or probable stent thrombosis (ST), was evaluated. RESULTS: After multivariable-adjusted analysis, in the CKD group, the MACE (adjusted hazard ratio [aHR]: 1.365, p = 0.004), all-cause death (aHR: 1.503, p = 0.004), noncardiac death (non-CD; aHR: 1.960, p = 0.004), and all-cause death or MI rates (aHR: 1.458, p = 0.002) were significantly higher in the NSTEMI group than in the STEMI group. In the non-CKD group, the non-CD rate (aHR: 1.78, p = 0.006) was also higher in the NSTEMI group. The CD, re-MI, any repeat revascularization, and ST rates were similar between groups. In the CKD group, from 6 months to 2 years after the index procedure, all-cause death, non-CD, and all-cause death or MI rates were significantly higher in the NSTEMI group than in the STEMI group. These results may be related to the higher non-CD rate in the NSTEMI group. CONCLUSIONS: In the era of contemporary newer-generation DES, NSTEMI showed a relatively higher non-CD rate than STEMI in both CKD and non-CKD groups.

Long-Term Clinical Outcomes and Its Predictors Between the 1- and 2-Stent Strategy in Coronary Bifurcation Lesions　- A Baseline Clinical and Lesion Characteristic-Matched Analysis.

BACKGROUND: Differences in the impact of the 1- or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions.Methods and Results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (pinteraction=0.008) and side branch calcification (pinteraction=0.010). CONCLUSIONS: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.

Feasibility of Aortic Annular Measurements Using Noncontrast-Enhanced Cardiac Computed Tomography in Preprocedural Evaluation of Transcatheter Aortic Valve Replacement: A Comparison With Contrast-Enhanced Computed Tomography.

OBJECTIVE: Noncontrast-enhanced (NCE) cross-sectional images other than contrast-enhanced (CE)-computed tomography (CT) may be necessary for annular sizing before transcatheter aortic valve replacement (TAVR), because of the risk of contrast-induced nephropathy. We aimed to investigate the feasibility of aortic annular measurements using NCE-CT in TAVR candidates by comparing them with CE-CT measurements. METHODS: We retrospectively enrolled 46 patients who underwent CT for the purpose of pre-TAVR evaluation (17 men; mean age, 82.3 ± 5.0 years). On CE and NCE examination, measurements of the average diameter and perimeter of aortic annulus were performed by 2 observers, and coronary ostial heights were measured. Differences in annular parameters and coronary ostial heights between NCE and CE examinations were assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs). RESULTS: Aortic annulus measurement values were significantly larger in the NCE examinations compared with those in the CE examinations according to both readers (mean differences of 0.8 mm for the average diameter and 2.1 mm for the perimeter according to observer 1, and 1.1 mm for the average diameter and 3.4 mm for the perimeter according to observer 2; ICC, 0.771-0.923). The mean difference between coronary ostial height measurement on NCE and CE examination was 0.6 mm for left coronary ostium (ICC, 0.795) and 0.7 mm for right coronary ostium (ICC, 0.802). No case showed disagreement between NCE and CE examinations for hypothetical valve sizing. CONCLUSIONS: Noncontrast-enhanced cardiac CT examination may be feasible for aortic annular measurements before TAVR and provides comparable measurement values to CE examination.

Clinical implication of neointimal burden in in-stent restenosis treated with drug-coated balloon.

BACKGROUND: Although drug-coated balloon (DCB) angioplasty is a well-established drug-eluting stent (DES) in-stent restenosis (ISR) strategy, there are minimal data regarding the association of neointimal burden on optical coherence tomography (OCT) before and after DCB and adverse clinical events. This study aimed to investigate the clinical impact of neointimal burden measured with OCT in patients with DES ISR after DCB angioplasty. METHODS: From 2010 through 2013, a total of 122 patients with 122 ISR lesions were treated with DCB, which was preceded and followed by OCT examination. Major adverse cardiac events (MACE, a composite occurrence of cardiovascular cardiac death, nonfatal myocardial infarction [MI], or target lesion revascularization [TLR]) were evaluated. RESULTS: MACE occurred in 27 patients (4 nonfatal MIs and 23 TLRs) during the follow-up (median: 55.3 months, interquartile range 43.1-66.0). The mean lumen area was significantly smaller (3.21 ± 2.42 mm2 vs. 4.80 ± 2.53 mm2 , p = .005) and the mean percentage of neointimal volume derived by OCT was greater (49.3 ± 9.2% vs. 38.3 ± 17.5%, p = .006) in patients with MACE before DCB angioplasty. The pre-procedural mean percentage of neointimal volume (cut-off 50%, area under the receiver operating characteristic [ROC] curve = 0.644, 95% confidence interval [CI] = 0.531-0.758, p = .022) and post-procedural mean percentage of neointimal volume (cut-off 25%, area under ROC curve = 0.659, 95% CI = 0.546-0.773, p = .012) were identified as significant parameters to predict MACE. CONCLUSION: The OCT-derived mean percentages of neointimal volume before and after DCB angioplasty can be important parameters for predicting future MACE in patients with DES ISR.

Safety and usefulness of a novel short track sliding balloon catheter.

OBJECTIVES: To evaluate the safety and technical utility of the short track sliding (STS) balloon catheter. BACKGROUND: An STS balloon catheter is designed to ensure a low profile at the shaft and perform distal anchoring using a single guidewire. However, its clinical practice with the STS balloon catheter has not been reported. METHODS: This prospective multi-center registry enrolled 100 patients with significant coronary artery disease who had undergone percutaneous coronary intervention using an STS balloon catheter at three hospitals in Korea from March 2019 to July 2020. Overall safety was assessed as any occurrences of device-related malfunction during the pre-dilation of the lesions. Its technical success rates of the kissing balloon technique or the distal anchoring technique using a single guidewire were also evaluated. RESULTS: Of the 118 lesions pre-dilated using the STS balloon, no significant complication was observed except for three significant coronary dissections, which were completely covered with stents. There was no incidence of balloon catheter malfunction, such as fracture, entrapment, or perforation. With 13 attempts of kissing ballooning techniques with the STS balloon with a 6F guiding catheter, all cases were successful. The distal anchoring techniques were attempted in 10 cases, the stent was successfully crossed to the target lesion in all 10 cases. CONCLUSIONS: The novel STS balloon catheter can be safely applied in routine coronary intervention with minimal complications. In addition, this catheter could be useful for performing the kissing balloon technique with a small-caliber guiding catheter and distal anchoring technique with a single guidewire.

Ten-Year Clinical Outcomes of Late-Acquired Stent Malapposition After Coronary Stent Implantation.

OBJECTIVE: The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy. CONCLUSIONS: The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.

Skin Perfusion Pressure Predicts Early Wound Healing After Endovascular Therapy in Chronic Limb Threatening Ischaemia.

OBJECTIVE: Skin perfusion pressure (SPP) has been proposed as a method to predict wound healing in chronic limb threatening ischaemia (CLTI). However, studies regarding the impact of SPP before and after endovascular therapy (EVT) on wound healing are limited. This study sought to evaluate the predictive value of SPP for early wound healing in CLTI treated by EVT. METHODS: Between January 2018 and June 2020, 236 limbs (172 patients) with CLTI that underwent SPP measurement before and after EVT were included. SPP was measured before and 24 - 48 hours after the procedure. Early wound healing was defined as the achievement of complete epithelisation of all wounds without major amputation within three months of EVT. RESULTS: Early wound healing was achieved in 145 (61.4%) limbs after EVT. Baseline SPP (44.1 ± 21.0 mmHg vs. 33.5 ± 21.7 mmHg; p < .001) and post-procedural SPP (61.8 ± 18.5 mmHg vs. 37.4 ± 19.9 mmHg; p < .001) were significantly higher in the wound healing (+) group than in the wound non-healing (-) group. The area under the receiver operating characteristics curve for early wound healing was 0.82 for post-procedural SPP with a cutoff value of 50 mmHg (sensitivity 74.5%, specificity 78.0%). The early wound healing rate was significantly higher with a post-procedural SPP ≥ 50 mmHg compared with a SPP < 50 mmHg (84.4% vs. 35.0%; p < .001). CONCLUSION: Post-procedural SPP with a cutoff value of 50 mmHg was capable of predicting early wound healing after EVT in CLTI.