The residual risk of inflammation and remnant cholesterol in acute coronary syndrome patients on statin treatment undergoing percutaneous coronary intervention.

BACKGROUND: Residual risk assessment for acute coronary syndrome (ACS) patients after sufficient medical management remains challenging. The usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing the level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patients needs to be evaluated. METHODS: Patients admitted for ACS on statin treatment who underwent percutaneous coronary intervention (PCI) between March 2016 and March 2019 were enrolled in the analysis. The included patients were stratified based on the levels of hsCRP and RC during hospitalization. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death. RESULTS: Among the 5778 patients, the median hsCRP concentration was 2.60 mg/L and the median RC concentration was 24.98 mg/dL. The RIR was significantly associated with ischemic events (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [aHR]: 1.52, 95% confidence interval [CI]: 1.01-2.30, P = 0.046), cardiac death (aHR: 1.77, 95% CI:1.02-3.07, P = 0.0418) and all-cause death (aHR: 2.00, 95% CI: 1.24-3.24, P = 0.0048). The RCR was also significantly associated with these outcomes, with corresponding values for the highest tertile of RC were 1.81 (1.21-2.73, P = 0.0043), 2.76 (1.57-4.86, P = 0.0004), and 1.72 (1.09-2.73, P = 0.0208), respectively. The risks of ischemic events (aHR: 2.80, 95% CI: 1.75-4.49, P < 0.0001), cardiac death (aHR: 4.10, 95% CI: 2.18-7.70, P < 0.0001), and all-cause death (aHR: 3.00, 95% CI, 1.73-5.19, P < 0.0001) were significantly greater in patients with both RIR and RCR (highest hsCRP and RC tertile) than in patients with neither RIR nor RCR (lowest hsCRP and RC tertile). Notably, the RIR and RCR was associated with an increased risk of ischemic events especially in patients with adequate low-density lipoprotein cholesterol (LDL-C) control (LDL-C < 70 mg/dl) (Pinteraction=0.04). Furthermore, the RIR and RCR provide more accurate evaluations of risk in addition to the GRACE score in these patients [areas under the curve (AUC) for ischemic events: 0.64 vs. 0.66, P = 0.003]. CONCLUSION: Among ACS patients receiving contemporary statin treatment who underwent PCI, high risks of both residual inflammation and cholesterol, as assessed by hsCRP and RC, were strongly associated with increased risks of ischemic events, cardiac death, and all-cause death.

Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial.

BACKGROUND: Previous randomised trials of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have reported conflicting results, in part because of treatment with different pharmacological regimens. We designed a large-scale trial examining bivalirudin with a post-PCI high-dose infusion compared with heparin alone, the regimens that previous studies have shown to have the best balance of safety and efficacy. METHODS: BRIGHT-4 was an investigator-initiated, open-label, randomised controlled trial conducted at 87 clinical centres in 63 cities in China. Patients with STEMI undergoing primary PCI with radial artery access within 48 h of symptom onset who had not received previous fibrinolytic therapy, anticoagulants, or glycoprotein IIb/IIIa inhibitors were randomly assigned (1:1) to receive bivalirudin with a post-PCI high-dose infusion for 2-4 h or unfractionated heparin monotherapy. There was no masking. Glycoprotein IIb/IIIa inhibitor use was reserved for procedural thrombotic complications in both groups. The primary endpoint was a composite of all-cause mortality or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. This trial is registered with ClinicalTrials.gov (NCT03822975), and is ongoing. FINDINGS: Between Feb 14, 2019, and April 7, 2022, a total of 6016 patients with STEMI undergoing primary PCI were randomly assigned to receive either bivalirudin plus a high-dose infusion after PCI (n=3009) or unfractionated heparin monotherapy (n=3007). Radial artery access was used in 5593 (93·1%) of 6008 patients. Compared with heparin monotherapy, bivalirudin reduced the 30-day rate of the primary endpoint (132 events [4·39%] in the heparin group vs 92 events [3·06%] in the bivalirudin group; difference, 1·33%, 95% CI 0·38-2·29%; hazard ratio [HR] 0·69, 95% CI 0·53-0·91; p=0·0070). All-cause mortality within 30 days occurred in 118 (3·92%) heparin-assigned patients and in 89 (2·96%) bivalirudin-assigned patients (HR 0·75; 95% CI 0·57-0·99; p=0·0420), and BARC types 3-5 bleeding occurred in 24 (0·80%) heparin-assigned patients and five (0·17%) bivalirudin-assigned patients (HR 0·21; 95% CI 0·08-0·54; p=0·0014). There were no significant differences in the 30-day rates of reinfarction, stroke, or ischaemia-driven target vessel revascularisation between the groups. Within 30 days, stent thrombosis occurred in 11 (0·37%) of bivalirudin-assigned patients and 33 (1·10%) of heparin-assigned patients (p=0·0015). INTERPRETATION: In patients with STEMI undergoing primary PCI predominantly with radial artery access, anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2-4 h significantly reduced the 30-day composite rate of all-cause mortality or BARC types 3-5 major bleeding compared with heparin monotherapy. FUNDING: Chinese Society of Cardiology Foundation (CSCF2019A01), and a research grant from Jiangsu Hengrui Pharmaceuticals.

Safety and Efficacy of Ticagrelor versus Clopidogrel in East Asian Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention Treated with Dual Antiplatelet Therapy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The treatment strategy for dual antiplatelet therapy (DAPT) with ticagrelor has been controversial in East Asian patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Our meta-analysis aimed to demonstrate whether intensified antithrombotic regimens with ticagrelor plus aspirin have more beneficial effects and fewer adverse events compared to those of clopidogrel plus aspirin in East Asian patients with ACS undergoing PCI. METHODS: We searched PubMed, Embase, Web of Science, ScienceDirect, Clinical Trials, Cochrane Library, and Chinese Clinical Trial Registry for randomized controlled trials (RCTs) comparing the efficacy of DAPT with ticagrelor or clopidogrel plus aspirin for secondary prevention of ACS in East Asian patients undergoing PCI. Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the metrics of choice for assessing treatment effects. The primary endpoint was bleeding events, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs, including cardiovascular death, nonfatal myocardial infarction [MI], and stroke), all-cause death, and definite/probable/possible stent thrombosis. The I2 index was used to assess heterogeneity. RESULTS: Six RCTs involving a total of 2,725 patients met the inclusion criteria. The incidence of all bleeding events with ticagrelor was higher than that with clopidogrel (RR, 1.65; 95% CI, 1.31-2.07), but the incidence of MACCE was not significantly different between the two groups (RR, 1.08; 95% CI, 0.54-2.16). All-cause death (RR, 1.10; 95% CI, 0.67-1.79), cardiovascular death (RR, 1.42; 95% CI, 0.68-2.98), nonfatal MI (RR, 0.92; 95% CI, 0.48-1.78), stroke (RR, 1.00; 95% CI, 0.40-2.50), and stent thrombosis (RR, 0.76; 95% CI, 0.19-2.98) were not statistically different between the two groups. CONCLUSION: Ticagrelor increased the risk of bleeding and did not increase treatment efficacy compared to that of clopidogrel in the East Asian population who have ACS treated with PCI.

Ticagrelor versus clopidogrel in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention.

OBJECTIVES: To evaluate the effectiveness and safety of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) undergoing complex percutaneous coronary intervention (PCI). BACKGROUND: It remains inconclusive whether ticagrelor is superior to clopidogrel in ACS patients undergoing complex PCI in real-world practice. METHODS: Based on an all-comers PCI registry, we compared the long-term effectiveness and safety between ticagrelor and clopidogrel in ACS patients undergoing complex PCI, defined as PCI procedures for complex lesions including bifurcation, chronic total occlusion, ostial, tortuous, calcific, diffused, thrombus-containing, and restenotic lesions. The primary ischemic outcome was a composite of cardiac death, myocardial infarction, or stroke. The safety outcome comprised Bleeding Academic Research Consortium (BARC) types 2, 3, and 5 bleeding. Propensity score matching (PSM) was performed to reduce bias. RESULTS: Among ACS patients who underwent complex PCI, 4373 (35.2%) and 8065 (64.8%) received dual antiplatelet therapy based on ticagrelor and clopidogrel, respectively. The incidences of composite ischemic events (before PSM: 1.74% vs. 2.84%; after PSM: 1.50% vs. 2.65%; p < 0.01 for both) and all-cause death (before PSM: 1.23% vs. 2.12%, p < 0.01; after PSM: 1.09% vs. 1.81%, p = 0.02) were significantly lower in the ticagrelor-treated than in the clopidogrel-treated group. There was no significant difference in BARC types 2, 3, and 5 bleeding between groups. CONCLUSIONS: Whilst the risk of major bleeding was comparable between the two drugs, ticagrelor was associated with a significantly lower risk of ischemic events than clopidogrel in ACS patients undergoing complex PCI.

Effectiveness and safety of bivalirudin in elderly patients with coronary artery disease undergoing percutaneous coronary intervention: A real-world study.

OBJECTIVE: To assess the effectiveness and safety of bivalirudin compared with heparin monotherapy in elderly patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Bivalirudin is recommended for periprocedural use in patients undergoing PCI who are of high bleeding risk. However, its safe and efficacious use in elderly patients, a typical high bleeding risk cohort, in real world practice is yet to be reported. METHODS: In this single center, real-world observational study, 4736 consecutive elderly patients who underwent PCI were enrolled. Of these, 1240 were treated with bivalirudin and 3496 with heparin according to the periprocedural anticoagulation strategies of PCI. The primary outcome was 12-month net adverse clinical events (NACE) defined as a composite of cardiac death, myocardial infarction, stroke, revascularization, or any bleeding. Propensity score matching (PSM) was used to balance baseline characteristics between groups. RESULTS: After PSM, bivalirudin was found to be associated with lower rates of NACE (19.1% vs. 24.7%, p = 0.002), cardiac death (2.7% vs. 4.3%, p = 0.038), and any bleeding (10.0% vs. 12.9%, p = 0.023) compared to heparin monotherapy. No differences were found in the incidences of myocardial infarction, stroke, revascularization, stent thrombosis (0.1% vs. 0.1%, p = 1.000), and major bleedings (0.5% vs. 0.5%, p = 1.000) between the two patient groups. CONCLUSION: In this real-world observational study, periprocedural use of bivalirudin in elderly patients who underwent PCI was associated with less cardiac death and any bleeding compared to heparin monotherapy, without increased risk of stent thrombosis.

Predictors and long-term outcomes of in-hospital switching from clopidogrel to ticagrelor among patients with acute coronary syndrome undergoing percutaneous coronary intervention.

This study evaluated clinical outcomes of switching from clopidogrel to ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). The clinical benefit of in-hospital switching from clopidogrel to ticagrelor in these patients remains unclear. Among patients with ACS initially receiving clopidogrel, logistic regression was used to identify independent predictors of switching to ticagrelor. Multivariable Cox regression was used to compare efficacy and safety between switching to ticagrelor and continuing clopidogrel. The primary endpoint was net adverse clinical events (NACEs) at 12 months, a composite of major adverse cardiovascular events (MACE) and Bleeding Academic Research Consortium (BARC) type 2/3/5 bleeding. Among 10,519 patients initially receiving clopidogrel, 1405 (13.4%) were switched to ticagrelor at discharge. Stent number, left main artery lesions, diabetes, male sex, age, estimated glomerular filtration rate of <45 ml/min/1.73 m2 , and history of PCI or stroke were identified as independent predictors of switching to ticagrelor. The rate of NACE (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.18-1.91) or BARC type 2/3/5 bleeding (HR: 2.01; 95% CI: 1.52-2.66) was significantly higher in patients switching to ticagrelor than in those continuing clopidogrel. The risk of MACE was comparable between both the groups (HR: 0.71; 95% CI: 0.41-1.22). In real-world practice, in-hospital switching from clopidogrel to ticagrelor was independently associated with several clinical factors. Patients switching to ticagrelor had a higher rate of NACE or BARC type 2/3/5 bleeding than those continuing clopidogrel, without any reduction in the MACE rate.

Determination of Optimal Fluoroscopic Angulations for Left Main Coronary Artery Ostial Interventions: 3-Dimensional Computed Tomography Validation.

Background: Current recommendations for the best views for the left main coronary artery (LMCA) ostium intervention are empirical. Objectives: To determine the optimal projection to visualize the LMCA ostium using only fluoroscopy. Methods: The optimal projection to visualize the LMCA ostium was determined using fluoroscopic images of superimposing the lowest points of the distal ends of two J tipped wires in the noncoronary cusp (NCC) and right coronary cusp (RCC). This was validated independently using 3-dimensional computed tomography (3D-CT) reconstruction. Results: Satisfactory images of the overlapping wires in NCC and RCC could be obtained in 90% (45/50). Between the fluoroscopic and the 3D-CT reconstruction approaches, the mean difference for NCC and RCC overlapping at horizontal axes is -1.8 with a 95% limit of agreement between -3.94 and 0.34 (p=0.10) and at vertical axes -1.6 with a 95% limit of agreement between -3.46 and 0.26 (p=0.09); and the mean difference for the optimal projection to visualize the LMCA ostium at horizontal axes is -3.22 with a 95% limit of agreement between -7.26 and 0.81 (p=0.11) and at vertical axes -2.31 with a 95% limit of agreement between -5.83 and 1.21 (p=0.09). The 3D angulation deviation for the optimal projection to visualize the LMCA ostium was 8.5° ± 4.7° when the LMCA ostium faced the NCC-RCC commissure (n = 32) and 22.3° ± 16.0° (p=0.009) when it did not (n = 13). Conclusions: The optimal projection for LMCA ostial intervention can be determined using fluoroscopic images of superimposing wires in the NCC and RCC when the LMCA ostium faces the NCC-RCC commissure, as was the case in 71% of the patients studied.

Impact of 6- versus 12-month dual antiplatelet therapy on clinical prognosis in patients with high bleeding risk: Insights from the 4-year results of the I LOVE IT 2 study.

OBJECTIVES: To explore the impact of 6- versus 12-month dual antiplatelet therapy (DAPT) on the clinical prognosis of high bleeding risk (HBR) patients. BACKGROUND: The optimal DAPT duration after percutaneous coronary intervention (PCI) in HBR patients is unclear. METHODS: This study is a post hoc analysis of the 4-year clinical follow-up results of the I LOVE IT 2 study. Prevalence and prognosis of HBR patients were explored, and clinical outcomes of HBR patients who underwent 6- versus 12-month DAPT were compared. The primary outcome was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The secondary outcomes were BARC type 2-5 bleeding and net clinical adverse events (NACE), defined as a composite of all-cause death, myocardial infarction (MI), ischemia-driven revascularization, stroke, stent thrombosis, or any bleeding events. RESULTS: HBR occurred in 440 of 2,737 patients (16.0%). HBR patients were associated with a higher risk of BARC type 3 or 5 bleeding (2.95 vs. 1.52%, p = .03), NACE (31.82 vs. 25.99%, p = .01), all-cause death (5.68 vs. 3.13%, p = .008) and stroke (9.09 vs. 3.83%, p < .001) than non-HBR patients at 4 years. There were no significant differences in BARC type 3 or 5 bleeding (3.07 vs. 2.76%, p = 1.00) or NACE rate (31.9 vs. 33.8%, p = .72) between patients who underwent 6- and 12-month DAPT. CONCLUSIONS: HBR patients are at a higher risk of long-term bleeding and ischemic events than non-HBR patients. The safety and efficacy of 6- and 12-month DAPT were comparable in HBR patients.

Comparison of the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome after risk stratification.

OBJECTIVE: This study aimed at comparing the effectiveness and safety of ticagrelor and clopidogrel in acute coronary artery syndrome (ACS) patients stratified by the Optimal Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) risk score. BACKGROUND: Although they provide a promising basis for treatment decisions, risk scores have not been utilized to optimize P2Y12 inhibitors for ACS patients. METHODS: In 2016-2019, 16,343 ACS patients who underwent percutaneous coronary intervention at the General Hospital of Northern Theater Command were enrolled and classified as low-risk (n = 9,841) or intermediate- to high-risk (n = 6,502) according to OPT-CAD risk score. Clinical outcomes for patients receiving clopidogrel or ticagrelor were compared within risk levels. Primary endpoint was ischemic events at 12 months. Propensity score matching (PSM) was used to balance groups. RESULTS: The risk of ischemic events (2.73% vs. 3.89%, p = .02) and all-cause mortality (1.75% vs. 2.86%, p = .01) were lower in the intermediate- to high-risk patients treated with ticagrelor than those treated with clopidogrel, without an excessive risk of major bleeding (3.71% vs. 3.95%, p = .65). Among low-risk patients, ticagrelor was associated with significantly increased bleeding risk (4.13% vs. 2.85%, p < .01) compared to clopidogrel, with no difference in ischemic risk (1.04% vs. 1.25%, p = .36). Results were consistent in PSM cohorts. CONCLUSIONS: Ticagrelor improves ischemic prognosis in intermediate- to high-risk patients but shows worse safety in low-risk patients compared to clopidogrel, supporting the effectiveness of risk score-guided decision making.

Impact of extended dual antiplatelet therapy on clinical prognosis in acute coronary syndrome patients with intermediate or high ischemic risk defined by the GRACE score.

OBJECTIVES: To evaluate the impact of extended dual antiplatelet therapy (DAPT) beyond 12 months in acute coronary syndrome (ACS) patients with intermediate-risk to high-risk of developing ischemia according to the Global Acute Coronary Event Registration (GRACE) score. BACKGROUND: The duration of optimal DAPT remains controversial in patients at higher risk of developing ischemia. METHODS: Overall, 9,309 ACS patients in the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study were stratified as low-risk ( n = 5,112) or intermediate-risk to high-risk (n = 4,197) according to the GRACE score on hospital discharge. Clinical outcomes at 12-24 months in patients with intermediate-to-high risk who completed 1-year DAPT without any adverse events were analyzed. The primary endpoint was 24-month net adverse clinical events (NACEs). RESULTS: Patients at intermediate-to-high-risk had significantly higher incidence of NACE (10.2 vs. 4.9%, p < .01) and ischemic events (8.3 vs. 3.8%, p < .01) than low-risk patients at 24 months. For patients at intermediate-to-high-risk, extended DAPT beyond 12 months was associated with lower risk of NACE (3.0 vs. 5.1%, p = .012), all-cause death (1.1 vs. 2.6%, p = .01), and cardiac death (0.6 vs. 1.8%, p = .01), without excessive risk of major bleeding events (0.3 vs. 0.5%, p = .47). Clinical outcomes in the propensity-matched cohort were consistent. CONCLUSIONS: ACS patients with intermediate-risk or high-ischemic risk may benefit from extended DAPT beyond 1 year, an outcome than requires further confirmation in large-scale randomized trials.

Impact of dual antiplatelet therapy duration on 1-year clinical outcomes in diabetic patients with acute coronary syndrome undergoing percutaneous coronary intervention: Insights from the real-world OPT-CAD study.

OBJECTIVES: To investigate the optimal dual antiplatelet therapy (DAPT) duration for diabetic patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). BACKGROUND: Diabetic patients are at high risk for ischemic and bleeding events when treated with antithrombotic agents after an ACS episode. METHODS: This post hoc study analyzed DAPT duration and clinical outcomes in diabetic patients with ACS who underwent PCI in the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) registry. The primary outcome was patient-oriented composite endpoints (PoCE) at 12 months; it was defined as a composite of all-cause mortality, all myocardial infarction (MI), stroke, or any revascularization. The safety outcome was bleeding events. RESULTS: In total, 1,773 diabetic patients with ACS were enrolled and treated with PCI in the OPT-CAD study. Premature DAPT discontinuation before 12 months was an independent PoCE predictor in diabetic patients (hazard ratio = 1.33, 95% confidence interval: 1.02-1.74, p = .006). It was associated with a significantly higher risk of PoCE (17.3 vs. 11.2%, p = .014) in diabetic patients with high risk factors (age ≥ 65 years or history of cardiovascular events including MI, stroke, or peripheral artery disease), but this association was not observed in those without high risk factors (10.4 vs. 9.1, p = .554). No excess bleeding risk was found in patients who received 12-month DAPT compared with those who discontinued DAPT prematurely. CONCLUSIONS: Premature DAPT discontinuation before 12 months was associated with increased risk of clinical events in diabetic patients with ACS after PCI, particularly in those with high-risk profiles.

Impact of six versus 12 months of dual antiplatelet therapy in patients with drug-eluting stent implantation after risk stratification with the residual SYNTAX score: Results from a secondary analysis of the I-LOVE-IT 2 trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation remains undetermined, especially for those at high risk of cardiac events postprocedure. OBJECTIVES: This study was aimed to investigate the impact of 6 versus 12 months of DAPT after DES implantation based on risk stratification with the residual SYNTAX score (rSS). METHODS: A total of 2737 patients in the I-LOVE-IT 2 trial were grouped according to rSS status (low rSS [rSS = 0, n = 1474] versus high rSS [rSS > 0, n = 1263]) and DAPT duration (6 months vs. 12 months). The primary endpoint was 12-month target lesion failure (TLF), and the major secondary endpoints were 12-month net adverse clinical events (NACE) and major bleeding. RESULTS: Incidences of TLF (5.2 vs. 7.4%, P = 0.01) and NACE (9.2 vs. 13.4%, P < 0.001) at 12 months were significantly higher in patients with high rSSs compared with patients with low rSSs. Landmark analysis showed that, in patients with high rSS, 12-month DAPT was associated with slightly lower risks of TLF (3.0% vs. 1.6%, P = 0.08) and NACE (7.0 vs. 4.4%, P = 0.054) compared with 6-month DAPT within 6 to 12 months after PCI. Patients with different DAPT durations had similar risks of bleeding both in the low and high rSS groups. CONCLUSIONS: Patients with high rSSs have an increased risk of TLF and NACE at 12 months after DES implantation. Twelve-month DAPT might be superior to 6-month DAPT in patients with high rSS for reducing adverse events within 6 to 12 months after PCI without excessive risk of bleeding. © 2017 Wiley Periodicals, Inc.

Ticagrelor vs clopidogrel when coadministered with bivalirudin in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Background: The optimal perioperative antithrombotic strategy for patients with acute coronary syndrome (ACS) during percutaneous coronary intervention (PCI) remains controversial. Objectives: To determine the safety and effectiveness of bivalirudin plus ticagrelor vs bivalirudin plus clopidogrel in patients with ACS undergoing PCI in the real world. Methods: Between March 2016 and March 2019, 7234 patients with ACS who had undergone PCI, received bivalirudin periprocedurally, and were prescribed ticagrelor or clopidogrel were enrolled in a single-center, all-comer, modern, retrospective cohort study. Incidence rates of 12-month ischemia (cardiac death, myocardial infarction, or stroke), all-cause death, Bleeding Academic Research Consortium (BARC) type 2,3,5 bleeding, and BARC type 3,5 bleeding were compared between different groups. Results: In total, 4960 patients received bivalirudin plus clopidogrel and 2274 patients received bivalirudin plus ticagrelor. Compared with bivalirudin plus clopidogrel, bivalirudin plus ticagrelor was associated with lower ischemic events (1.74% vs 2.84%; relative risk, 0.61; 95% CI, 0.41-0.91; P = .02) and stroke (0.05% vs 1.01%, P < .001) within 12 months after PCI without excessive risk of bleeding (BARC type 2,3,5 bleeding: 4.49% vs 3.76%, P = .22; BARC type 3,5 bleeding: 2.84% vs 2.02%, P = .08). The beneficial effects of bivalirudin plus ticagrelor were consistent among subgroups. Conclusion: As an initial treatment strategy, bivalirudin plus ticagrelor could reduce the 12-month risk of ischemic events compared with bivalirudin plus clopidogrel significantly without increasing the bleeding risk in ACS patients undergoing PCI.

Net clinical benefit of clopidogrel versus ticagrelor in elderly patients carrying CYP2C19 loss-of-function variants with acute coronary syndrome after percutaneous coronary intervention.

BACKGROUND AND AIMS: Elderly patients with acute coronary syndrome (ACS) tend to choose clopidogrel over potent P2Y12 receptor inhibitor such as ticagrelor after percutaneous coronary intervention (PCI) in China considering higher risks of bleeding. CYP2C19 genotype is regarded as a major factor influencing the efficacy of clopidogrel. The present study aims to investigate the efficacy and safety of ticagrelor relative to clopidogrel in elderly ACS patients after PCI in China with reduced CYP2C19 metabolism. METHODS: Between January 2016 and March 2019, 2751 ACS patients over 65 years old with CYP2C19 loss-of-function (LOF) variants after PCI were enrolled. All patients were treated with aspirin and P2Y12 receptor inhibitor, among whom 2056 received clopidogrel and 695 received ticagrelor. Net adverse clinical events (NACE), a composite of cardiac death, myocardial infarction (MI), ischemic stroke, target vessel revascularization and clinically relevant bleeding including Bleeding Academic Research Consortium (BARC) types 2, 3, 5 bleeding, were compared between the two groups at 12 months after PCI. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the two groups. RESULTS: Before and after PSM, NACE was significantly increased in ticagrelor group compared with clopidogrel group at 12 months post PCI (Before PSM, 15.18% vs. 25.61% p<0.001; After PSM, 11.66% vs. 26.01% p<0.001). MACE was comparable between the two groups (Before PSM, 5.45% vs. 5.32% p>0.999; After PSM, 3.59% vs. 5.38% p=0.146). BARC types 2, 3, 5 bleeding events were significantly increased in patients treated with ticagrelor relative to clopidogrel (Before PSM, 10.31% vs. 21.01% p<0.001; After PSM, 8.22% vs. 21.38% p<0.001), which was mainly attributed to a higher incidence of BARC type 2 bleeding events in ticagrelor group (Before PSM, 8.12% vs. 18.56% p<0.001; After PSM, 6.43% vs. 18.83% p<0.001). CONCLUSIONS: In the present real-world study, selection of ticagrelor over clopidogrel showed a significant increase in NACE with a higher incidence of bleeding and similar ischemic events in elderly ACS patients carrying CYP2C19 LOF variants after PCI.

Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia.

BACKGROUND: A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia. METHODS AND RESULTS: A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; P<0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; P<0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups. CONCLUSIONS: Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.

Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk: The OPT-BIRISK Randomized Clinical Trial.

Importance: Purinergic receptor P2Y12 (P2Y12) inhibitor monotherapy after a certain period of dual antiplatelet therapy (DAPT) may be an attractive option of maintenance antiplatelet treatment for patients undergoing percutaneous coronary intervention (PCI) who are at both high bleeding and ischemic risk (birisk). Objective: To determine if extended P2Y12 inhibitor monotherapy with clopidogrel is superior to ongoing DAPT with aspirin and clopidogrel after 9 to 12 months of DAPT after PCI in birisk patients with acute coronary syndromes (ACS). Design, Setting, and Participants: This was a multicenter, double-blind, placebo-controlled, randomized clinical trial including birisk patients with ACS who had completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months at 101 China centers between February 2018 and December 2020. Study data were analyzed from April 2023 to May 2023. Interventions: Patients were randomized either to clopidogrel plus placebo or clopidogrel plus aspirin for an additional 9 months. Main Outcomes and Measures: The primary end point was Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events (MACCE; the composite of all-cause death, myocardial infarction, stroke or clinically driven revascularization). The primary end point was tested for superiority, and the MACCE end point was tested for sequential noninferiority and superiority. Results: A total of 7758 patients (mean [SD] age, 64.8 [9.0] years; 4575 male [59.0%]) were included in this study. The primary end point of BARC types 2, 3, or 5 bleeding occurred in 95 of 3873 patients (2.5%) assigned to clopidogrel plus placebo and 127 of 3885 patients (3.3%) assigned to clopidogrel plus aspirin (hazard ratio [HR], 0.75; 95% CI, 0.57-0.97; difference, -0.8%; 95% CI, -1.6% to -0.1%; P = .03). The incidence of MACCE was 2.6% (101 of 3873 patients) in the clopidogrel plus placebo group and 3.5% (136 of 3885 patients) in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96; difference, -0.9%; 95% CI, -1.7% to -0.1%; P < .001 for noninferiority; P = .02 for superiority). Conclusions and Relevance: Among birisk patients with ACS who completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months before randomization, an extended 9-month clopidogrel monotherapy regimen was superior to continuing DAPT with clopidogrel in reducing clinically relevant bleeding without increasing ischemic events. Trial Registration: ClinicalTrials.gov Identifier: NCT03431142.

N-terminal pro-B-type natriuretic peptide improves the predictive value of CHA2 DS2 -VASc risk score for long-term cardiovascular events in acute coronary syndrome patients with atrial fibrillation.

BACKGROUND: It is important to identify patients with co-morbid acute coronary syndrome (ACS) and atrial fibrillation (AF) at high risk and adopt proper management strategies to improve their prognosis. HYPOTHESIS: The addition of N-terminal pro-B-type natriuretic peptide (NT-proBNP) could improve predictive value for long-term cardiovascular events beyond the CHA2 DS2 -VASc score in patients with co-morbid ACS and AF. METHODS: A total of 1223 patients with baseline NT-proBNP between January 2016 and December 2019 were included in the study. The primary endpoint was all-cause death at 12 months. The secondary outcomes included 12-month cardiac death and major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, or stroke. RESULTS: A higher serum of NT-proBNP levels was strongly associated with increased risks of all-cause death (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI], 1.03-1.07), cardiac death (adjusted HR: 1.05, 95% CI, 1.03-1.07), and MACCE (adjusted HR: 1.04, 95% CI, 1.02-1.06). The prognostic accuracy of the CHA2 DS2 -VASc score was improved when combined with NT-proBNP to yield a 9%, 11%, and 7% increment for the discrimination of long-term risk for all-cause mortality (area under curve [AUC]: from 0.64 to 0.73), cardiac death (AUC: from 0.65 to 0.76), and MACCE (AUC: from 0.62 to 0.69), respectively. CONCLUSIONS: In patients with ACS and AF, NT-proBNP is a potential biomarker to enhance risk discrimination for all-cause death, cardiac death, and MACCE in combination with the CHA2 DS2 -VASc score.

Rivaroxaban in patients with abdominal aortic aneurysm and high-sensitivity C-reactive protein elevation (BANBOO): study protocol for a randomized, controlled trial.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a fatal disease due to the tendency to rupture. The drug treatment for small AAA without surgical indications has been controversial. Previous studies showed that high-sensitivity C-reactive protein (hs-CRP) had become a potential biomarker of the disease, and the anti-inflammatory effect of rivaroxaban for AAA had been well established. Thus, we hypothesized that rivaroxaban could control the progression of AAA in patients with hs-CRP elevation. METHODS: The study is a prospective, open-label, randomized, controlled clinical trial. Sixty subjects are recruited from the General Hospital of Northern Theatre Command of China. Subjects are randomly assigned (1:1) to the intervention arm (rivaroxaban) or control arm (aspirin). The primary efficacy outcome is the level of serum hs-CRP at 6 months. The secondary outcomes include imaging examination (the maximal diameter of AAA, the maximal thickness of mural thrombus, and the length of aneurysm), major adverse cardiovascular and cerebrovascular events (MACCE, including AAA transformation, non-fatal myocardial infarction, acute congestive heart failure, stent thrombosis, ischemia-driven target vessel revascularization, vascular amputation, stroke, cardiovascular death, and all-cause death), and other laboratory tests (troponin T, interleukin 6, D-dimer, and coagulation function). DISCUSSION: The BANBOO trial tested the effect of rivaroxaban on the progression of AAA in patients with elevated Hs-CRP for the first time. TRIAL REGISTRATION: ChiCTR2100051990, ClinicalTrials.gov, registered on 12 October 2021.

Effect of dual antiplatelet therapy prolongation in acute coronary syndrome patients with both high ischemic and bleeding risk: insight from the OPT-CAD study.

Background: In current clinical practice, controversy remains regarding the clinical benefits of prolonged dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients facing high risks of both ischemia and bleeding ("bi-risk") following percutaneous coronary intervention (PCI). This study aimed to investigate the feasibility of identifying a group of bi-risk ACS patients after PCI using the OPT-BIRISK criteria, emphasizing extended DAPT treatment safety and efficacy beyond 12 months in these bi-risk ACS after PCI in real-world conditions. Methods: This analysis compared extended DAPT and single antiplatelet therapy (SAPT) at 12-24 months in ACS patients undergoing PCI complicated with both ischemic and bleeding risk as defined by OPT-BIRISK criteria without premature DAPT discontinuation before 9 months or major clinical adverse events within 12 months. This was a post hoc analysis of the Optimal antiPlatelet Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) study. The main research outcome was the incidence of ischemic events within 12-24 months, which was determined as a composite of stroke, myocardial infarction, and cardiac death events. Through propensity score matching (PSM), groups were balanced. For the external validation of the OPT-BIRISK criteria to identify a bi-risk ACS patient, ischemic events, BARC 2, 3, 5 bleeding events, and BARC 3, 5 bleeding events at 5 years were analyzed. Results: The total number of ACS patients analyzed in this analysis was 7,049, of whom 4,146 (58.8%) were bi-risk patients and 2,903 (41.2%) were not. The frequency of ischemic events was significantly different between the two groups at 5 years (11.70% vs. 5.55%, P < 0.001), and the incidence of BARC 2,3,5 bleeding was significantly higher in the bi-risk group (6.90% vs. 4.03%, P < 0.001) than in the non-bi-risk group. Among the bi-risk patients without any clinical adverse events within 12 months that underwent extended DAPT treatment (n = 2,374, 75.7%) exhibited a lower risk of stroke at 12-24 months (1.10% vs. 2.10%, P = 0.036) relative to those that underwent SAPT (n = 763, 24.3%), while bleeding risk did not differ significantly between these groups. PSM cohort analysis results were consistent with those of overall group analyses. Conclusion: In conclusion, the findings showed that using the OPT-BIRISK criteria could help physicians identify ACS patients at a high risk of developing recurrent ischemia and bleeding episodes after PCI. Compared to antiplatelet monotherapy, a strategy of extended DAPT may offer potential benefits in lowering the risk of stroke without carrying a disproportionately high risk of serious bleeding problems among these patients who were event-free after a year of DAPT.

Dietary Inflammatory Index and All-Cause Mortality in Older Adults with Hypertension: Results from NHANES.

Both diet and inflammation are strongly associated with hypertension. However, the relationship between the dietary inflammatory index (DII) and the prognosis of hypertensive patients over 65 years of age is unclear. The objective of this study is to investigate the correlation between DII and all-cause mortality in older adults with hypertension. Data were obtained from the 2011−2018 National Health and Nutrition Examination Survey (NHANES) and followed for survival through December 31, 2019. DII was calculated by the 24 h dietary history interview. Cox proportional hazards models were used to investigate the associations. A total of 2531 participants were finally included. During a median follow-up of 4.33 years, 471 participants were determined as all-cause mortality. After adjusting for confounding factors, DII was positively correlated with the risk of all-cause mortality (HR = 1.08, 95% CI = 1.01−1.16). Compared with the anti-inflammatory diet group (DII < 0), the pro-inflammatory diet group (DII > 0) had a 54% increased risk of all-cause death (HR = 1.54, 95% CI = 1.13−2.10). The results were robust in subgroup and sensitivity analyses. DII was positively correlated with the all-cause mortality of elderly hypertensive patients. The results provided an aid to dietary evaluation in the nonpharmacologic management of hypertension.