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Background Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and the most common systemic disorder associated with uveitis in childhood. Uveitis is more common in JIA patients who are antinuclear antibody (ANA)-positive, have an early-onset disease, and have oligoarticular arthritis. JIA-associated uveitis (JIA-uveitis) is typically anterior, chronic, bilateral, nongranulomatous, and asymptomatic. Visual outcomes in JIA-uveitis have improved with current screening and treatment options; however, many patients fail to respond or do not achieve long-lasting remission. Baricitinib, an oral selective Janus kinase (JAK)1 and 2 inhibitor, may impact key cytokines implicated in the pathogenesis of JIA-uveitis or ANA-positive uveitis, representing a potential novel treatment option for disease management. Methods The multicenter, phase 3 trial will be conducted using an open-label Bayesian design. The study will enroll at least 20 and up to 40 patients aged 2 to Discussion This is the first pediatric clinical trial to assess the clinical effectiveness and safety of a JAK inhibitor in JIA-uveitis or chronic ANA-positive uveitis. A novel Bayesian design is used to assess the efficacy of baricitinib, including an adalimumab reference arm, in this small patient population with unmet medical need. Trial registration EudraCT 2019-000119-10. Registered on January 4, 2019; NCT04088409. Registered on September 12, 2019

OBJECTIVE: To investigate the use of prasugrel after percutaneous coronary intervention (PCI) in African American (AA) patients presenting with acute coronary syndrome (ACS). BACKGROUND: AA patients are at higher risk for adverse cardiovascular outcomes after PCI and may derive greater benefit from the use of potent antiplatelet therapy. METHODS: Using the multicenter PROMETHEUS observational registry of ACS patients treated with PCI, we grouped patients by self-reported AA or other races. Clinical outcomes at 90-day and 1-year included non-fatal myocardial infarction (MI), major adverse cardiac events (composite of death, MI, stroke, or unplanned revascularization) and major bleeding. RESULTS: The study population included 2,125 (11%) AA and 17,707 (89%) non-AA patients. AA patients were younger, more often female (46% vs. 30%) with a higher prevalence of diabetes mellitus, chronic kidney disease, and prior coronary intervention than non-AA patients. Although AA patients more often presented with troponin (+) ACS, prasugrel use was much less common in AA vs. non-AA (11.9% vs. 21.4%, respectively, P = 0.001). In addition, the use of prasugrel increased with the severity of presentation in non-AA but not in AA patients. Multivariable logistic regression showed AA race was an independent predictor of reduced use of prasugrel (0.42 [0.37-0.49], P

BACKGROUND: Clinical trial data studies suggest superiority of prasugrel over clopidogrel in patients with diabetes. However, the use, safety and efficacy profile of prasugrel in unselected diabetic patients presenting with acute coronary syndromes (ACS) remain unclear. METHODS: PROMETHEUS was a prospective multicenter observational study of 19,919 ACS PCI patients enrolled between 2010 and 2013. The primary endpoint was 90-day major adverse cardiovascular events (MACE), comprising all-cause death, myocardial infarction, stroke or unplanned revascularization. The safety endpoint was bleeding requiring hospitalization. RESULTS: We identified 7580 (38%) subjects with and 12,329 (62%) without diabetes. Diabetic patients were older and had significantly higher rates of cardiovascular risk factors. However, they were less likely to receive prasugrel (18.2% vs. 21.7%). Use of prasugrel did not increase with the severity of clinical presentation in diabetics, whereas, among non-diabetics, prescription of prasugrel was higher in NSTEMI and STEMI compared to unstable angina. The 90-day and 1-year adjusted risk of MACE was greater in diabetics (at 1 year: 22.7% vs. 16.5%; HR 1.22 [1.14-1.33], p

BACKGROUND: Potent P2Y12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. METHODS: PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. RESULTS: The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). CONCLUSIONS: Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction.

Objectives This study sought to compare clinical outcomes in a contemporary acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) cohort stratified by chronic kidney disease (CKD) status. Background Patients with CKD exhibit high risks for both thrombotic and bleeding events, thus complicating decision making regarding antiplatelet therapy in the setting of ACS. Methods The PROMETHEUS study was a multicenter observational study comparing outcomes with prasugrel versus clopidogrel in ACS PCI patients. Major adverse cardiac events (MACE) at 90 days and at 1 year were defined as a composite of death, myocardial infarction, stroke, or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Cox regression multivariable analysis was performed for adjusted associations between CKD status and clinical outcomes. Hazard ratios for prasugrel versus clopidogrel treatment were generated using propensity score stratification. Results The total cohort included 19,832 patients, 28.3% with and 71.7% without CKD. CKD patients were older with greater comorbidities including diabetes and multivessel disease. Prasugrel was less often prescribed to CKD versus non-CKD patients (11.0% vs. 24.0%, respectively; p Conclusions Although risks for 1-year MACE were significantly higher in ACS PCI patients with versus without CKD, prasugrel use was 50% lower in patients with renal impairment. Irrespective of CKD status, outcomes associated with prasugrel use were not significant after propensity adjustment. These data highlight the need for randomized studies evaluating the optimal antiplatelet therapy in CKD patients with ACS.

BACKGROUND AND OBJECTIVES: We sought to determine the frequency of use and association between prasugrel and outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) in clinical practice. METHODS: PROMETHEUS was a multicenter observational registry of acute coronary syndrome patients undergoing PCI from 8 centers in the United States that maintained a prospective PCI registry for patient outcomes. The primary end points were major adverse cardiovascular events at 90days, a composite of all-cause death, nonfatal myocardial infarction, stroke, or unplanned revascularization. Major bleeding was defined as any bleeding requiring hospitalization or blood transfusion. Hazard ratios (HRs) were generated using multivariable Cox regression and stratified by the propensity to treat with prasugrel. RESULTS: Of 19,914 patients (mean age 64.4years, 32% female), 4,058 received prasugrel (20%) and 15,856 received clopidogrel (80%). Prasugrel-treated patients were younger with fewer comorbid risk factors compared with their counterparts receiving clopidogrel. At 90days, there was a significant association between prasugrel use and lower major adverse cardiovascular event (5.7% vs 9.6%, HR 0.58, 95% CI 0.50-0.67, P

Background Stroke represents a potentially calamitous complication among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) even though its rates are relatively low. Data on the distribution of stroke occurrence over time and its overlap with myocardial infarction (MI) and bleeding after PCI is scarce. Purpose We sought to compare the occurrence and impacts of stroke, MI and bleeding on subsequent mortality in ACS patients undergoing PCI in contemporary clinical practice. Methods A total of 19,914 ACS patients who underwent PCI in the PROMETHEUS multi-center observational study were analyzed. We calculated the cumulative stroke incidence at 30 days and 1 year using Kaplan Meier (KM) method. We also compared the distribution of stroke, myocardial infarction (MI) and bleeding across time and evaluated the overlap between their occurrences. Predictors of 1 year stroke occurrence were identified through multivariable Cox-regression and stroke, MI and bleeding were entered as time-updated covariates to estimate their individual effects on subsequent mortality. Results Of the total number of patients, 244 patients (1.5%) had a stroke within 1 year. 48 of these patients also experienced an MI while another 48 patients experienced a bleeding event. Furthermore, 14 of these overlapping patients experienced a stroke, MI and bleeding event, all within the 1-year follow-up. Patients who sustained a stroke were more likely to have a prior history of cerebrovascular disease, peripheral artery disease, MI and heart failure compared to those who did not have a stroke. Mortality risk was significantly higher among those with stroke versus those without stroke (adjusted HR 4.84, p Conclusion When compared with MI and bleeding, stroke had a substantially stronger impact on mortality that attenuated rapidly over time among ACS patients undergoing PCI. Optimization of modifiable risk factors and medication adherence are essential parts of management of stroke following PCI for ACS.

While overall mortality in cardiovascular disease has declined, some groups such as females with diabetes are still at increased risk for worse outcome after ACS. We aimed to compare 1-year outcomes between female and male ACS patients after PCI stratified by the presence of diabetes mellitus (DM

Bleeding is a risk of potent antiplatelet therapy. Anemia is associated with increased bleeding. We sought to examine the rates of prasugrel use, thienopyridine switching and clinical outcomes by presence of anemia in contemporary percutaneous coronary intervention (PCI) for acute coronary syndrome

Stent length is an independent risk factor for adverse cardiovascular events after percutaneous coronary intervention (PCI) with first generation drug eluting stents (DES). We examined the associations between stent length and clinical events in patients treated with second generation DES.

Prasugrel and ticagrelor are potent P2Y12 ADP receptor inhibitors that have greater clinical efficacy compared with clopidogrel, but more non-CABG bleeding. There are no direct comparisons of clinical outcomes between the drugs with follow-up through 1 year. This retrospective study compared 1 year

Background: Multivessel (MV) disease is present in a significant number of patients with non-ST-segment elevation myocardial infarction (NSTEMI). The optimal revascularization strategy in these patients is uncertain. Methods: PROMETHEUS was a multicenter observational study of patients undergoing

Background: African American (AA) patients are at high risk for adverse cardiovascular outcomes after PCI, thus providing a rationale for use of potent P2Y12 inhibitors in such individuals. However, whether or not race is a determinant of prasugrel versus clopidogrel use in acute coronary syndrome (

The determinants of clinical decision-making for potent platelet inhibition with prasugrel versus clopidogrel in real-world patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) remain poorly characterized. The purpose of this study was to identify factors

The contemporary incidence, associated factors and implications of stroke after acute coronary syndromes (ACS) managed with percutaneous coronary intervention (PCI) and novel antiplatelet drugs is unknown. We sought to characterize the incidence, predictors and impact of stroke on subsequent

Randomized data have shown that prasugrel is superior to clopidogrel in reducing ischemic risk including unplanned revascularization, albeit with increased bleeding. Greater stent length is also an independent correlate of adverse events after percutaneous coronary intervention (PCI). We sought to