Association of Age- and Body Mass Index-Stratified High On-Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients.

BACKGROUND: Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on-treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. METHODS AND RESULTS: The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m2 or >22.6 kg/m2). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P=0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P=0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P=0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140-1.688]; P=0.001). No differences were shown in major bleeding. CONCLUSIONS: HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

The Use of Coronary Imaging for Predicting Future Cardiovascular Events.

Background: Despite advancements in coronary artery disease (CAD) treatment with drug-eluting stent, its morbidity and mortality remain high. In context, intravascular imaging-guided percutaneous coronary intervention (PCI) is increasingly recommended for better clinical outcomes in patient with CAD. Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), as one of the intravascular imaging methods, is effective in detecting lipid-rich plaques, which is crucial for identifying high-risk or vulnerable plaques employing near-infrared light. High lipid core burden, as identified by NIRS-IVUS, correlates with an increased risk of adverse cardiac events and shows varying degrees of efficacy in plaque management and event prevention. Summary: This article addresses about how NIRS-IVUS can be used to predict event of CAD. The study highlights the crucial role of NIRS-IVUS in predicting future cardiovascular events. Findings indicate that the presence of high lipid core burden is related to increased risks of periprocedural myocardial infarction and reduced coronary flow during PCI. The study also outlines the predictive value of NIRS-IVUS in non-culprit lesions, where plaques with high lipid core burden significantly increase the occurrence of major adverse cardiac events as demonstrated in the PROSPECT II trial. In terms of therapeutic strategies, the study reviews the effectiveness of high-intensity lipid-lowering strategies in stabilizing vulnerable plaques, as evidenced in trials such as the YELLOW and PACMAN AMI trials. Key Messages: NIRS-IVUS emerges as a valuable diagnostic tool in treating CAD. It effectively identifies vulnerable plaques and aids in predicting and preventing future adverse cardiac events. However, to enhance its practicality and promote widespread adoption in clinical settings, further long-term outcome research of NIRS-IVUS-guided PCI is necessary. These efforts can potentially make NIRS-IVUS a more accessible and indispensable tool in cardiovascular disease management.

Quantitative Coronary Angiography vs Intravascular Ultrasonography to Guide Drug-Eluting Stent Implantation: A Randomized Clinical Trial.

Importance: Although intravascular ultrasonography (IVUS) guidance promotes favorable outcomes after percutaneous coronary intervention (PCI), many catheterization laboratories worldwide lack access. Objective: To investigate whether systematic implementation of quantitative coronary angiography (QCA) to assist angiography-guided PCI could be an alternative strategy to IVUS guidance during stent implantation. Design, Setting, and Participants: This randomized, open-label, noninferiority clinical trial enrolled adults (aged ≥18 years) with chronic or acute coronary syndrome and angiographically confirmed native coronary artery stenosis requiring PCI. Patients were enrolled in 6 cardiac centers in Korea from February 23, 2017, to August 23, 2021, and follow-up occurred through August 25, 2022. All principal analyses were performed according to the intention-to-treat principle. Interventions: After successful guidewire crossing of the first target lesion, patients were randomized in a 1:1 ratio to receive either QCA- or IVUS-guided PCI. Main Outcomes and Measures: The primary outcome was target lesion failure at 12 months, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. The trial was designed assuming an event rate of 8%, with the upper limit of the 1-sided 97.5% CI of the absolute difference in 12-month target lesion failure (QCA-guided PCI minus IVUS-guided PCI) to be less than 3.5 percentage points for noninferiority. Results: The trial included 1528 patients who underwent PCI with QCA guidance (763; mean [SD] age, 64.1 [9.9] years; 574 males [75.2%]) or IVUS guidance (765; mean [SD] age, 64.6 [9.5] years; 622 males [81.3%]). The post-PCI mean (SD) minimum lumen diameter was similar between the QCA- and IVUS-guided PCI groups (2.57 [0.55] vs 2.60 [0.58] mm, P = .26). Target lesion failure at 12 months occurred in 29 of 763 patients (3.81%) in the QCA-guided PCI group and 29 of 765 patients (3.80%) in the IVUS-guided PCI group (absolute risk difference, 0.01 percentage points [95% CI, -1.91 to 1.93 percentage points]; hazard ratio, 1.00 [95% CI, 0.60-1.68]; P = .99). There was no difference in the rates of stent edge dissection (1.2% vs 0.7%, P = .25), coronary perforation (0.2% vs 0.4%, P = .41), or stent thrombosis (0.53% vs 0.66%, P = .74) between the QCA- and IVUS-guided PCI groups. The risk of the primary end point was consistent regardless of subgroup, with no significant interaction. Conclusions and Relevance: Findings of this randomized clinical trial indicate that QCA and IVUS guidance during PCI showed similar rates of target lesion failure at 12 months. However, due to the lower-than-expected rates of target lesion failure in this trial, the findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT02978456.

Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial.

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.

Prediction of In-Hospital Mortality for Ischemic Cardiogenic Shock Requiring Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Clinical outcome of ischemic cardiogenic shock (CS) requiring extracorporeal membrane oxygenation is highly variable, necessitating appropriate assessment of prognosis. However, a systemic predictive model estimating the mortality of refractory ischemic CS is lacking. The PRECISE (Prediction of In-Hospital Mortality for Patients With Refractory Ischemic Cardiogenic Shock Requiring Veno-Arterial Extracorporeal Membrane Oxygenation Support) score was developed to predict the prognosis of refractory ischemic CS due to acute myocardial infarction. METHODS AND RESULTS: Data were obtained from the multicenter CS registry RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) that consists of 322 patients with acute myocardial infarction complicated by refractory ischemic CS requiring extracorporeal membrane oxygenation support. Fifteen parameters were selected to assess in-hospital mortality. The developed model was validated internally and externally using an independent external cohort (n=138). Among 322 patients, 138 (42.9%) survived postdischarge. Fifteen predictors were included for model development: age, diastolic blood pressure, hypertension, chronic kidney disease, peak lactic acid, serum creatinine, lowest left ventricular ejection fraction, vasoactive inotropic score, shock to extracorporeal membrane oxygenation insertion time, extracorporeal cardiopulmonary resuscitation, use of intra-aortic balloon pump, continuous renal replacement therapy, mechanical ventilator, successful coronary revascularization, and staged percutaneous coronary intervention. The PRECISE score yielded a high area under the receiver-operating characteristic curve (0.894 [95% CI, 0.860-0.927]). External validation and calibration resulted in competent sensitivity (area under the receiver-operating characteristic curve, 0.895 [95% CI, 0.853-0.930]). CONCLUSIONS: The PRECISE score demonstrated high predictive performance and directly translates into the expected in-hospital mortality rate. The PRECISE score may be used to support clinical decision-making in ischemic CS (www.theprecisescore.com). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

High platelet reactivity strongly predicts early stent thrombosis in patients with drug-eluting stent implantation.

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58-16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07-21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028.

Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound.

BACKGROUND: Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have shown comparable outcomes in guiding percutaneous coronary intervention (PCI). However, their comparative effectiveness in complex coronary artery lesions remains unclear. OBJECTIVES: This study compared the effectiveness and safety of OCT-guided vs IVUS-guided PCI for complex coronary artery lesions. METHODS: This was a prespecified, main subgroup analysis of complex coronary artery lesions in the OCTIVUS (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention) trial, which included unprotected left main disease, bifurcation disease, an aorto-ostial lesion, a chronic total occlusion, a severely calcified lesion, an in-stent restenotic lesion, a diffuse long lesion, or multivessel PCI. The primary endpoint was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization. RESULTS: In 2,008 randomized patients, 1,475 (73.5%) underwent imaging-guided PCI for complex coronary artery lesions; 719 (48.7%) received OCT-guided and 756 (51.3%) IVUS-guided PCI. At a median follow-up of 2.0 years, primary endpoint event had occurred in 47 patients (6.5%) in the OCT-guided group and in 56 patients (7.4%) in the IVUS-guided group (HR: 0.87; 95% CI: 0.59-1.29; P = 0.50). These findings were consistent in adjusted analyses. The incidence of contrast-induced nephropathy was similar between the 2 groups (1.9% vs 1.5%; P = 0.46). The incidence of major procedural complications was lower in the OCT-guided group than in the IVUS-guided group (1.7% vs 3.4%; P = 0.03). CONCLUSIONS: Among patients with complex coronary artery lesions, OCT-guided PCI showed a similar risk of primary composite event of death from cardiac causes, target vessel-related myocardial infarction, or target vessel revascularization as compared with IVUS-guided PCI. (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention [OCTIVUS]; NCT03394079).

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

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.

Predictors of in-hospital mortality after successful weaning of venoarterial extracorporeal membrane oxygenation in cardiogenic shock.

Limited knowledge exists regarding the predictors of mortality after successful weaning of venoarterial extracorporeal membrane oxygenation (ECMO). We aimed to identify predictors of in-hospital mortality in patients with cardiogenic shock (CS) after successful weaning from ECMO. Data were obtained from a multicenter registry of CS. Successful ECMO weaning was defined as survival with minimal mean arterial pressure (> 65 mmHg) for > 24 h after ECMO removal. The primary outcome was in-hospital mortality after successful ECMO weaning. Among 1247 patients with CS, 485 received ECMO, and 262 were successfully weaned from ECMO. In-hospital mortality occurred in 48 patients (18.3%). Survivors at discharge differed significantly from non-survivors in age, cardiovascular comorbidities, cause of CS, left ventricular ejection fraction, and use of adjunctive therapy. Five independent predictors for in-hospital mortality were identified: use of continuous renal replacement therapy (odds ratio 5.429, 95% confidence interval [CI] 2.468-11.940; p < 0.001), use of intra-aortic balloon pump (3.204, 1.105-9.287; p = 0.032), diabetes mellitus (3.152, 1.414-7.023; p = 0.005), age (1.050, 1.016-1.084; p = 0.003), and left ventricular ejection fraction after ECMO insertion (0.957, 0.927-0.987; p = 0.006). Even after successful weaning of ECMO, patients with irreversible risk factors should be recognized, and careful monitoring should be done for sign of deconditioning.

Impact of diabetes on long-term outcomes of bifurcation percutaneous coronary intervention. An analysis from the BIFURCAT registry.

BACKGROUND: It is still unclear the impact of diabetes mellitus (DM) in complex coronary lesions treated with percutaneous coronary intervention (PCI) which themselves are at increased incidence of adverse events. METHODS: BIFURCAT registry encompassed patients treated with PCI for coronary bifurcation lesion from the COBIS III and the RAIN registry. The primary endpoint was the occurrence of major cardiovascular adverse event (MACE), a composite and mutual exclusive of all-cause death or myocardial infarction (MI) or target-lesion revascularization (TLR). A total of 5537 patients were included in the analysis and 1834 (33%) suffered from DM. RESULTS: After a median follow-up of 21 months, diabetic patients had a higher incidence of MACE (17% vs. 9%, p < 0.001), all-cause mortality (9% vs. 4%, p < 0.001), TLR (5% vs. 3%, p = 0.001), MI (4% vs. 2%, p < 0.001), and stent thrombosis (ST) (2% vs. 1%, p = 0.007). After multivariate analysis, diabetes remained significantly associated with MACE (hazard ratio [HR]: 1.37; confidence interval [CI]: 1.13-1.65; p = 0.001), all-cause death (HR: 1.65; 95% CI: 1.24-2.19, p = 0.001), TLR (HR: 1.45; CI: 1.03-2.04; p = 0.031) and ST (HR: 1.73, CI: 1.04-2.88; p = 0.036), but not with MI (HR: 1.34; CI: 0.93-1.92; p = 0.11). Among diabetics, chronic kidney disease (HR: 2.99; CI: 2.21-4.04), baseline left ventricular ejection fraction (HR: 0.98; CI: 0.97-0.99), femoral access (HR: 1.62; CI: 1.23-2.15), left main coronary artery (HR: 1.44; CI: 1.06-1.94), main branch diameter (HR: 0.79; CI: 0.66-0.94) and final kissing balloon (HR: 0.70; CI: 0.52-0.93) were independent predictors of MACE at follow-up. CONCLUSIONS: Patients with DM treated with PCI for coronary bifurcations have a worse prognosis due to higher incidence of MACE, all-cause mortality, TLR and ST compared to the non-diabetics.

Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Moderate-Intensity Statin With Ezetimibe Combination Therapy vs High-Intensity Statin Monotherapy in Patients at Very High Risk of Atherosclerotic Cardiovascular Disease: A Post Hoc Analysis From the RACING Randomized Clinical Trial.

Importance: High-intensity statin is strongly recommended in patients at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD). However, concerns about statin-associated adverse effects result in underuse of this strategy in practice. Objective: To evaluate the outcomes of a moderate-intensity statin with ezetimibe combination in VHR and non-VHR patients with ASCVD. Design, Setting, and Participants: This was a post hoc analysis of the Randomized Comparison of Efficacy and Safety of Lipid Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease (RACING) open-label, multicenter, randomized clinical trial. The study was conducted from February 2017 to December 2018 at 26 centers in Korea. Study participants included patients with documented ASCVD. Data were analyzed from April to June 2022. Interventions: Patients were randomly assigned to moderate-intensity statin with ezetimibe (rosuvastatin, 10 mg, with ezetimibe, 10 mg) or high-intensity statin monotherapy (rosuvastatin, 20 mg). Patients at VHR for ASCVD were defined according to the 2018 American Heart Association/American College of Cardiology guidelines. Main Outcomes and Measures: The primary end point was the 3-year outcome of cardiovascular death, coronary or peripheral revascularization, hospitalization of cardiovascular events, or nonfatal stroke. Results: A total of 3780 patients (mean [SD] age, 64 [10] years; 2826 male [75%]) in the RACING trial, 1511 (40.0%) were categorized as VHR, which was associated with a greater occurrence of the primary end point (hazard ratio [HR], 1.42; 95% CI, 1.15-1.75). There was no significant difference in the primary end point between those who received combination therapy and high-intensity statin monotherapy among patients with VHR disease (11.2% vs 11.7%; HR, 0.96; 95% CI, 0.71-1.30) and non-VHR disease (7.7% vs 8.7%; HR, 0.88; 95% CI, 0.66-1.18). The median low-density lipoprotein cholesterol (LDL-C) level was significantly lower in the combination therapy group than in the high-intensity statin group (VHR, 1 year: 57 [47-71] mg/dL vs 65 [53-78] mg/dL; non-VHR, 1 year: 58 mg/dL vs 68 mg/dL; P < .001). Furthermore, in both the VHR and non-VHR groups, combination therapy was associated with a significantly greater mean change in LDL-C level (VHR, 1 year: -19.1 mg/dL vs -10.1 mg/dL; 2 years: -22.3 mg/dL vs -13.0 mg/dL; 3 years: -18.8 mg/dL vs -9.7 mg/dL; non-VHR, 1 year: -23.7 mg/dL vs -12.5 mg/dL; 2 years: -25.2 mg/dL vs -15.1 mg/dL; 3 years: -23.5 mg/dL vs -12.6 mg/dL; all P < .001) and proportion of patients with LDL-C level less than 70 mg/dL (VHR, 1 year: 73% vs 58%; non-VHR, 1 year: 72% vs 53%; P < .001). Discontinuation or dose reduction of the lipid-lowering drug due to intolerance occurred less frequently in the combination therapy group (VHR, 4.6% vs 7.7%; P = .02; non-VHR, 5.0% vs 8.7%; P = .001). Conclusions and Relevance: Results suggest that the outcomes of ezetimibe combination observed in the RACING trial were consistent among patients at VHR of ASCVD. Trial Registration: ClinicalTrials.gov Identifier: NCT03044665.

Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: The OCTIVUS Randomized Clinical Trial.

BACKGROUND: Intravascular imaging-guided percutaneous coronary intervention (PCI) with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) showed superior clinical outcomes compared with angiography-guided PCI. However, the comparative effectiveness of OCT-guided and IVUS-guided PCI regarding clinical outcomes is unknown. METHODS: In this prospective, multicenter, open-label, pragmatic trial, we randomly assigned 2008 patients with significant coronary artery lesions undergoing PCI in a 1:1 ratio to undergo either an OCT-guided or IVUS-guided PCI. The primary end point was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year, which was powered for noninferiority of the OCT group compared with the IVUS group. Safety outcomes were also assessed. RESULTS: At 1 year, primary end point events occurred in 25 of 1005 patients (Kaplan-Meier estimate, 2.5%) in the OCT group and in 31 of 1003 patients (Kaplan-Meier estimate, 3.1%) in the IVUS group (absolute difference, -0.6 percentage points; upper boundary of one-sided 97.5% CI, 0.97 percentage points; P<0.001 for noninferiority). The incidence of contrast-induced nephropathy was similar (14 patients [1.4%] in the OCT group versus 15 patients [1.5%] in the IVUS group; P=0.85). The incidence of major procedural complications was lower in the OCT group than in the IVUS group (22 [2.2%] versus 37 [3.7%]; P=0.047), although imaging procedure-related complications were not observed. CONCLUSIONS: In patients with significant coronary artery lesions, OCT-guided PCI was noninferior to IVUS-guided PCI with respect to the incidence of a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year. The selected study population and lower-than-expected event rates should be considered in interpreting the trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique number: NCT03394079.

A Randomized, Multicenter, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Quadruple Combination of Amlodipine, Losartan, Rosuvastatin, and Ezetimibe in Patients with Concomitant Essential Hypertension and Dyslipidemia.

BACKGROUND: Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia. OBJECTIVE: We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia. METHODS: This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145 patients were randomized to receive A/L/R/E, A/L, or L/R/E. The primary endpoints were the average change in the low-density lipoprotein cholesterol (LDL-C) level in the A/L/R/E and A/L groups and the sitting systolic blood pressure (sitSBP) in the A/L/R/E and L/R/E groups. The numbers of patients with adverse drug reactions (ADRs) were compared as safety variables. RESULTS: The average percentage change in the LDL-C level as the least squares mean (LSM) from the baseline LDL-C level at the end of the 8-week treatment was - 59.0% in the A/L/R/E group and 0.2% in the A/L group (LSM difference - 59.2, 95% confidence interval [CI] - 68.1 to - 50.4; p < 0.0001). The average change in the sitSBP as the LSM was - 15.8 mmHg in the A/L/R/E group and -4.7 mmHg in the L/R/E group (LSM difference - 11.1, 95% CI - 16.8 to - 5.4; p = 0.0002). No ADRs occurred in the A/L/R/E group. CONCLUSIONS: A/L/R/E as an SPC could be an effective treatment for patients with hypertension and dyslipidemia without significant safety issues. CLINICAL TRIALS REGISTRATION: NCT04074551 (registered 30 August 2019).

Effect of Cilostazol on Patients With Diabetes Who Underwent Endovascular Treatment for Peripheral Artery Disease.

Background No large-scale study has compared the clinical impact of triple antiplatelet therapy (TAPT: aspirin, clopidogrel, and cilostazol) and dual antiplatelet therapy (DAPT) on adverse limb events in patients with diabetes after endovascular therapy (EVT) for peripheral artery disease. Thus, we investigate the effect of cilostazol added to a DAPT on the clinical outcomes after EVT in patients with diabetes using a nationwide, multicenter, real-world registry. Methods and Results A total of 990 patients with diabetes who underwent EVT were enrolled from the retrospective cohorts of a Korean multicenter EVT registry and were divided according to the antiplatelet regimen (TAPT [n=350; 35.4%] versus DAPT [n=640; 64.6%]). After propensity score matching based on clinical characteristics, a total of 350 pairs were compared for clinical outcomes. The primary end points were major adverse limb events, a composite of major amputation, minor amputation, and reintervention. For the matched study groups, the lesion length was 125.4±102.0 mm, and severe calcification was observed in 47.4%. The technical success rate (96.9% versus 94.0%; P=0.102) and the complication rate (6.9% versus 6.6%; P>0.999) were similar between the TAPT and DAPT groups. At 2-year follow-up, the incidence of major adverse limb events (16.6% versus 19.4%; P=0.260) did not differ between the 2 groups. However, the TAPT group showed less minor amputation than the DAPT group (2.0% versus 6.3%; P=0.004). In multivariate analysis, TAPT was an independent predictor of minor amputation (adjusted hazard ratio, 0.354 [95% CI, 0.158-0.794]; P=0.012). Conclusions In patients with diabetes undergoing EVT for peripheral artery disease, TAPT did not decrease the incidence of major adverse limb events but may be associated with a decreased risk of minor amputation.

Two-Year clinical outcomes after coronary bifurcation stenting in older patients from Korea and Italy.

Background: Older patients who treated by percutaneous coronary intervention (PCI) are at a higher risk of adverse cardiac outcomes. We sought to investigate the clinical impact of bifurcation PCI in older patients from Korea and Italy. Methods: We selected 5,537 patients who underwent bifurcation PCI from the BIFURCAT (comBined Insights from the Unified RAIN and COBIS bifurcAtion regisTries) database. The primary outcome was a composite of target vessel myocardial infarction, clinically driven target lesion revascularization, and stent thrombosis at two years. Results: In patients aged ≥75 years, the mean age was 80.1 ± 4.0 years, 65.2% were men, and 33.7% had diabetes. Older patients more frequently presented with chronic kidney disease (CKD), severe coronary calcification, and left main coronary artery disease (LMCA). During a median follow-up of 2.1 years, older patients showed similar adverse clinical outcomes compared to younger patients (the primary outcome, 5.7% vs. 4.5%; p = 0.21). Advanced age was not an independent predictor of the primary outcome (p = 0.93) in overall patients. Both CKD and LMCA were independent predictors regardless of age group. Conclusions: Older patients (≥75 years) showed similar clinical outcomes to those of younger patients after bifurcation PCI. Advanced age alone should not deter physicians from performing complex PCIs for bifurcation disease.

Comparison of efficacy and safety between third-dose triple and third-dose dual antihypertensive combination therapies in patients with hypertension.

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.

Effect of rosuvastatin 20 mg versus rosuvastatin 5 mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial.

BACKGROUND: Current guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients. TRIAL DESIGN: This investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months. CONCLUSIONS: The SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.