Intravascular Imaging-Guided or Angiography-Guided Complex PCI.

BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).

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.

Immediate versus staged complete revascularization in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: results from a prematurely discontinued randomized multicenter trial.

BACKGROUND: We aimed to compare clinical outcomes between immediate and staged complete revascularization in primary percutaneous coronary intervention (PCI) for treating ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). METHODS: A total of 248 patients were enrolled in a prospective, randomized, and multicenter registry. Immediate revascularization was defined as one-time PCI of culprit and non-culprit lesions at the initial procedure. Staged revascularization was defined as PCI of non-culprit lesions at a later date (mean, 4.4 days; interquartile range, 1-11.4), following initial culprit revascularization. The end points were major adverse cardiovascular events (MACE; composite of total death, recurrent myocardial infarction, and revascularization), any individual components of MACE, cardiac death, stent thrombosis, and stroke at 12 months. RESULTS: During a follow-up of 1 year, MACE occurred in 12 patients (11.6%) in the immediate revascularization group and in 8 patients (7.5%) in staged revascularization group (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.65-3.91). The incidence of total death was numerically higher in the immediate group than in the staged group (9.7% vs 2.8%, HR 3.53, 95% CI 0.97-12.84); There were no significant differences between the 2 groups in risks of any individual component of MACE, cardiac death, stroke, and in-hospital complications, such as need for transfusion, bleeding, acute renal failure, and acute heart failure. This study was prematurely terminated due to halt of production of everolimus-eluting stents (manufactured as PROMUS Element by Boston Scientific, Natick, Massachusetts). CONCLUSIONS: Due to its limited power, no definite conclusion can be drawn regarding complete revascularization strategy from the present study. Further large randomized clinical trials would be warranted to confirm optimal timing of complete revascularization for patients with STEMI and MVD.

Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial.

Importance: Discontinuing aspirin after short-term dual antiplatelet therapy (DAPT) was evaluated as a bleeding reduction strategy. However, the strategy of ticagrelor monotherapy has not been exclusively evaluated in patients with acute coronary syndromes (ACS). Objective: To determine whether switching to ticagrelor monotherapy after 3 months of DAPT reduces net adverse clinical events compared with ticagrelor-based 12-month DAPT in patients with ACS treated with drug-eluting stents. Design, Setting, and Participants: A randomized multicenter trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea. Follow-up was completed in October 2019. Interventions: Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529). Main Outcomes and Measures: The primary outcome was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization). Prespecified secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events. Results: Among 3056 patients who were randomized (mean age, 61 years; 628 women [20%]; 36% ST-elevation myocardial infarction), 2978 patients (97.4%) completed the trial. The primary outcome occurred in 59 patients (3.9%) receiving ticagrelor monotherapy after 3-month DAPT and in 89 patients (5.9%) receiving ticagrelor-based 12-month DAPT (absolute difference, -1.98% [95% CI, -3.50% to -0.45%]; hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.92]; P = .01). Of 10 prespecified secondary outcomes, 8 showed no significant difference. Major bleeding occurred in 1.7% of patients with ticagrelor monotherapy after 3-month DAPT and in 3.0% of patients with ticagrelor-based 12-month DAPT (HR, 0.56 [95% CI, 0.34 to 0.91]; P = .02). The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the ticagrelor monotherapy after 3-month DAPT group (2.3%) vs the ticagrelor-based 12-month DAPT group (3.4%) (HR, 0.69 [95% CI, 0.45 to 1.06]; P = .09). Conclusions and Relevance: Among patients with acute coronary syndromes treated with drug-eluting stents, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year. The study population and lower than expected event rates should be considered in interpreting the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02494895.

Comparison of Spot versus Long Stenting for Femoropopliteal Artery Disease.

BACKGROUND: Optimal stenting strategy for long femoropopliteal artery lesions still remains undefined. Longer stent length has been shown to be associated with increased risk of restenosis. We sought to compare the efficacy of spot versus long stenting in the treatment of femoropopliteal artery disease. METHODS: This study was designed as a multicenter randomized controlled trial to compare immediate and mid-term outcomes of spot versus long primary stenting for femoropopliteal arterial lesions. A total of 125 patients were randomized 1:1 to spot stenting group (n = 59) or long stenting group (n = 66). RESULTS: All lesions were treated with self-expanding bare nitinol stents. Baseline clinical and lesion characteristics were similar between the 2 groups except for male gender and current smoker. The mean lesion length was 24.1 ± 8.8 cm. Technical success was achieved in all patients. The 1-year primary patency and TLR-free (target lesion revascularization) survival did not differ significantly between the 2 groups. However, the spot stenting group showed a trend toward higher primary patency (86.1% vs. 72.7%, P = 0.158) and TLR-free survival (94.2% vs. 82.5%, P = 0.120). The total stented length (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.00-1.01, P = 0.011) and age (HR 0.94, 95% CI 0.90-1.00, P = 0.035) were independent predictors of restenosis. CONCLUSIONS: The spot stenting appears to be more favorable than the long stenting in terms of primary patency and TLR-free survival, although the difference was not statistically significant. The stented length was an independent predictor of restenosis.

P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent: The SHARE Randomized Clinical Trial.

Importance: P2Y12 inhibitor monotherapy after dual antiplatelet therapy (DAPT; a P2Y12 inhibitor plus aspirin) for a brief duration has recently emerged as an attractive alternative for patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent. Objective: To investigate whether P2Y12 inhibitor monotherapy after 3 months of DAPT was noninferior to 12 months of DAPT following PCI with a drug-eluting stent. Design, Setting, and Participants: The Short-Term Dual Antiplatelet Therapy After Deployment of Bioabsorbable Polymer Everolimus-Eluting Stent (SHARE) open-label, noninferiority randomized clinical trial was conducted from December 15, 2017, through December 14, 2020. Final 1-year clinical follow-up was completed in January 2022. This study was a multicenter trial that was conducted at 20 hospitals in South Korea. Patients who underwent successful PCI with bioabsorbable polymer everolimus-eluting stents were enrolled. Interventions: Patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (n = 694) or 12 months of DAPT (n = 693). Main Outcomes and Measures: The primary outcome was a net adverse clinical event, a composite of major bleeding (based on Bleeding Academic Research Consortium type 3 or type 5 bleeding) and major adverse cardiac and cerebrovascular events (cardiac death, myocardial infarction, stent thrombosis, stroke, or ischemia-driven target lesion revascularization) between 3 and 12 months after the index PCI. The major secondary outcomes were major adverse cardiac and cerebrovascular events and major bleeding. The noninferiority margin was 3.0%. Results: Of the total 1452 eligible patients, 65 patients were excluded before the 3-month follow-up, and 1387 patients (mean [SD] age, 63.0 [10.7] years; 1055 men [76.1%]) were assigned to P2Y12 inhibitor monotherapy (n = 694) or DAPT (n = 693). Between 3 and 12 months of follow-up, the primary outcome (using Kaplan-Meier estimates) occurred in 9 patients (1.7%) in the P2Y12 inhibitor monotherapy group and in 16 patients (2.6%) in the DAPT group (absolute difference, -0.93 [1-sided 95% CI, -2.64 to 0.77] percentage points; P < .001 for noninferiority). For the major secondary outcomes (using Kaplan-Meier estimates), major adverse cardiac and cerebrovascular events occurred in 8 patients (1.5%) in the P2Y12 inhibitor monotherapy group and in 12 patients (2.0%) in the DAPT group (absolute difference, -0.49 [95% CI, -2.07 to 1.09] percentage points; P = .54). Major bleeding occurred in 1 patient (0.2%) in the P2Y12 inhibitor monotherapy group and in 5 patients (0.8%) in the DAPT group (absolute difference, -0.60 [95% CI, -1.33 to 0.12] percentage points; P = .10). Conclusions and Relevance: In patients with coronary artery disease undergoing PCI with the latest generation of drug-eluting stents, P2Y12 inhibitor monotherapy after 3-month DAPT was not inferior to 12-month DAPT for net adverse clinical events. Considering the study population and lower-than-expected event rates, further research is required in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT03447379.

Intravascular Imaging and Angiography Guidance in Complex Percutaneous Coronary Intervention Among Patients With Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. Objective: To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes. Design, Setting, and Participants: This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024. Interventions: Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone. Main Outcomes and Measures: The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Results: Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02). Conclusions and Relevance: In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Intravascular Imaging-Guided Optimization of Complex Percutaneous Coronary Intervention by Sex: A Subgroup Analysis of the RENOVATE-COMPLEX-PCI Trial.

Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Impact of Intravascular Imaging-Guided Stent Optimization According to Clinical Presentation in Patients Undergoing Complex PCI.

BACKGROUND: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI). OBJECTIVES: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation. METHODS: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69). CONCLUSIONS: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872).

Effectiveness and Safety of a Fixed-Dose Combination of Valsartan and Rosuvastatin (Rovatitan® Tablet) in Patients with Concomitant Hypertension and Hyperlipidemia: An Observational Study.

Purpose: This study aimed to assess the effectiveness and safety of a fixed-dose combination of rosuvastatin and valsartan (Rovatitan®) in Korean patients with concomitant hypertension and hyperlipidemia. Patients and Methods: A total of 1008 eligible patients with concomitant hypertension and hyperlipidemia were enrolled and treated for 12 weeks. Both upward and downward drug dose titrations were allowed based on the investigator's discretion. This study evaluated the effectiveness of the study drug, defined by the percentage of patients achieving the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) treatment targets. Additionally, regression analyses were conducted to evaluate the factors associated with the effectiveness and safety of the study drug. Of the 1008 patients enrolled in the study, 911 were analyzed for clinical effectiveness. Results: At 12 weeks, 84.6% and 75.9% of patients treated with the study drug achieved their BP and LDL-C targets, respectively, and 64.8% of patients achieved both targets simultaneously. Furthermore, the percentage of patients who achieved their BP and LDL-C treatment targets demonstrated a trend across the respective risk groups; the higher the risk group, the lower the success of attaining the respective target. This trend was also observed regardless of the prior antihypertensive and/or lipid-lowering treatments. According to regression analysis, poor metabolic profiles, including a higher body mass index (BMI) and higher BP and LDL-C levels at baseline, were significantly associated with treatment failure for BP. Among the 1005 patients included in the safety analysis, 17 patients (1.7%) experienced serious adverse events; however, none were considered related to the study drug. Conclusion: The study drug used for the treatment of concomitant hypertension and hyperlipidemia in a real-world setting was effective and was well tolerated. Therefore, the study drug is suggested as a good alternative to increase patient convenience and compliance, particularly in those taking multiple medications.

Efficacy and safety of moderate-intensity statin with ezetimibe combination therapy in patients after percutaneous coronary intervention: a post-hoc analysis of the RACING trial.

Background: Moderate-intensity statin role with ezetimibe combination therapy following percutaneous coronary intervention (PCI) has not been thoroughly investigated, particularly compared to high-intensity statin monotherapy. We aimed to investigate the effect of ezetimibe combination with moderate-intensity statin in patients with atherosclerotic cardiovascular disease following PCI. Methods: This was a post-hoc analysis of a subset of patients who underwent PCI in the RACING trial. At 26 centres in South Korea, patients with atherosclerotic cardiovascular disease (ASCVD) were randomly assigned 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 prespecified endpoints of the RACING trial were used. The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, and nonfatal stroke. Event rates between the two groups were compared using log-rank tests, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression analysis. Consistent with the RACING trial, the primary and secondary efficacy endpoints were evaluated using an intention-to-treatment approach, and the safety endpoints were assessed in the safety population. The RACING trial was registered at ClinicalTrials.gov (NCT03044665). Findings: Between Feb 14, 2017, and Dec 18, 2018, 3780 participants were enrolled in the RACING trial. Prior history of PCI was found in 2497 patients (67%, median 64 years, 79% male), and was associated with higher rates of the primary endpoint (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.06-1.69; p = 0.014). Among patients with prior PCI, moderate-intensity statin therapy with ezetimibe combination versus high-intensity statin therapy did not increase the risk of the primary endpoint (HR, 0.95; 95% CI, 0.74-1.24; p = 0.781). The proportion of patients with low-density lipoprotein cholesterol (LDL-C) <70 mg/dL at 1, 2, and 3 years was 74%, 76%, and 73%, respectively, in the combination therapy group, and was significantly higher than that in the high-intensity statin monotherapy group (57%, 62%, and 59%, respectively, all p < 0.001). Discontinuation of lipid-lowering drugs occurred less frequently in the combination group (4.2% vs. 7.6%, p = 0.001). Interpretation: The effects of ezetimibe combination therapy observed in the RACING trial were consistently preserved among patients with ASCVD following PCI. Ezetimibe combination could be considered as a suitable therapeutic strategy to achieve strict control of LDL-C and reduce drug intolerance in patients who underwent PCI. Funding: Hanmi Pharmaceutical, Seoul, South Korea.

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.

Perioperative Antiplatelet Strategy in Patients Undergoing Noncardiac Surgery Within One Year After Percutaneous Coronary Intervention.

BACKGROUND: The optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. METHODS: Patients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. RESULTS: Among 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). CONCLUSIONS: The APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.

Clinical Benefit of Intravascular Imaging Compared With Conventional Angiography in Left Main Coronary Artery Intervention.

BACKGROUND: The RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) demonstrated that intravascular imaging-guided percutaneous coronary intervention (PCI) improved clinical outcome compared with angiography-guided PCI for patients with complex coronary artery lesions. This study aims to assess whether the prognostic benefit of intravascular imaging-guided procedural optimization persists in patients undergoing PCI for left main coronary artery disease. METHODS: Of 1639 patients enrolled in the RENOVATE-COMPLEX-PCI, 192 patients with left main coronary artery disease were selected for the current prespecified substudy. Selected patients were randomly assigned to either the intravascular imaging-guided PCI group (n=138) or the angiography-guided PCI group (n=54). The primary end point was target vessel failure defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: At a median follow-up of 2.1 years (interquartile range 1.1 to 3.0 years), intravascular imaging-guided PCI was associated with lower incidence of primary end point compared with angiography-guided PCI (6.8% versus 25.1%; hazard ratio, 0.31 [95% CI, 0.13-0.76]; P=0.010). This significant reduction in primary end point was mainly driven by a lower risk of cardiac death or spontaneous target vessel-related myocardial infarction (1.6% versus 12.7%; hazard ratio, 0.16 [95% CI, 0.03-0.82]; P=0.028). Intravascular imaging-guided PCI was independently associated with a lower risk of primary end point, even after adjusting for various clinical factors (hazard ratio, 0.29 [95% CI, 0.12-0.72]; P=0.007). CONCLUSIONS: Intravascular imaging-guided PCI showed clinical benefit over angiography-guided PCI for left main coronary artery disease in reducing the risk of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03381872.

Ticagrelor Monotherapy After 3-Month Dual Antiplatelet Therapy in Acute Coronary Syndrome by High Bleeding Risk: The Subanalysis From the TICO Trial.

BACKGROUND AND OBJECTIVES: Identifying patients with high bleeding risk (HBR) is important when making decisions for antiplatelet therapy strategy. This study evaluated the impact of ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT) according to HBR in acute coronary syndrome (ACS) patients treated with drug eluting stents (DESs). METHODS: In this post-hoc analysis of the TICO trial, HBR was defined by 2 approaches: meeting Academic Research Consortium for HBR (ARC-HBR) criteria or Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent DAPT (PRECISE-DAPT) score ≥25. The primary outcome was a 3-12 months net adverse clinical event (composite of major bleeding and adverse cardiac and cerebrovascular events). RESULTS: Of the 2,980 patients without adverse events during the first 3 months after DES implantation, 453 (15.2%) were HBR by ARC-HBR criteria and 504 (16.9%) were HBR by PRECISE-DAPT score. The primary outcome rate was higher in HBR versus non-HBR patients (by ARC-HBR criteria: hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.76-4.69; p<0.001; by PRECISE-DAPT score: HR, 3.09; 95% CI, 1.92-4.98; p<0.001). Ticagrelor monotherapy after 3-month DAPT was associated with lower primary outcome rate than ticagrelor-based 12-month DAPT regardless of HBR by ARC-HBR criteria, with similar magnitudes of therapy effect for HBR and non-HBR patients (p-interaction=0.400). Results were consistent by PRECISE-DAPT score (p-interaction=0.178). CONCLUSIONS: In ACS patients treated with DESs, ticagrelor monotherapy after 3-month DAPT was associated with lower rate of adverse clinical outcomes regardless of HBR, with similar magnitudes of therapy effect between HBR and non-HBR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02494895.

A randomized, open-label, parallel, multi-center Phase IV study to compare the efficacy and safety of atorvastatin 10 and 20 mg in high-risk Asian patients with hypercholesterolemia.

BACKGROUND: Although accumulating evidence suggests a more extensive reduction of low-density lipoprotein cholesterol (LDL-C), it is unclear whether a higher statin dose is more effective and cost-effective in the Asian population. This study compared the efficacy, safety, and cost-effectiveness of atorvastatin 20 and 10 mg in high-risk Asian patients with hypercholesterolemia. METHODS: A 12-week, open-label, parallel, multicenter, Phase IV randomized controlled trial was conducted at ten hospitals in the Republic of Korea between October 2017 and May 2019. High-risk patients with hypercholesterolemia, defined according to 2015 Korean guidelines for dyslipidemia management, were eligible to participate. We randomly assigned 250 patients at risk of atherosclerotic cardiovascular disease to receive 20 mg (n = 124) or 10 mg (n = 126) of atorvastatin. The primary endpoint was the difference in the mean percentage change in LDL-C levels from baseline after 12 weeks. Cost-effectiveness was measured as an exploratory endpoint. RESULTS: LDL-C levels were reduced more significantly by atorvastatin 20 mg than by 10 mg after 12 weeks (42.4% vs. 33.5%, p < 0.0001). Significantly more patients achieved target LDL-C levels (<100 mg/dL for high-risk patients, <70 mg/dL for very high-risk patients) with atorvastatin 20 mg than with 10 mg (40.3% vs. 25.6%, p < 0.05). Apolipoprotein B decreased significantly with atorvastatin 20mg versus 10 mg (-36.2% vs. -29.9%, p < 0.05). Lipid ratios also showed greater improvement with atorvastatin 20 mg than with 10 mg (total cholesterol/high-density lipoprotein cholesterol ratio, -33.3% vs. -29.4%, p < 0.05; apolipoprotein B/apolipoprotein A1 ratio, -36.7% vs. -31.4%, p < 0.05). Atorvastatin 20 mg was more cost-effective than atorvastatin 10 mg in terms of both the average and incremental cost-effectiveness ratios. Safety and tolerability of atorvastatin 20 mg were comparable to those of atorvastatin 10 mg. CONCLUSION: In high-risk Asian patients with hypercholesterolemia, atorvastatin 20 mg was both efficacious in reducing LDL-C and cost-effective compared with atorvastatin 10 mg.

Correction: A randomized, open-label, parallel, multi-center Phase IV study to compare the efficacy and safety of atorvastatin 10 and 20 mg in high-risk Asian patients with hypercholesterolemia.

[This corrects the article DOI: 10.1371/journal.pone.0245481.].

Impact of genetic variants on major bleeding after percutaneous coronary intervention based on a prospective multicenter registry.

Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08-5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding.Trial registration: NCT02707445 ( https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1 ).