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To improve access to high-quality HIV care in underserved regions of Western Washington (WA) State, we collaborated with the WA State Department of Health (DOH) and community partners to launch four satellite HIV clinics. Here, we describe this innovative clinical care model, present an estimate of costs, and evaluate patient care outcomes, including virologic suppression rates. To accomplish this, we assessed virologic suppression rates 12 months before and 12 months after the satellite clinics opened, comparing people living with HIV (PLWH) who enrolled in the satellite clinics versus all PLWH in the same regions who did not. We also determined virologic suppression rates in 2015 comparing satellite clinic versus non-satellite clinic patients and compared care quality indicators between the satellite clinics and the parent academic clinic. Results demonstrate that the change in virologic suppression rate 12 months before to 12 months after the satellite clinics opened was higher for patients who enrolled in the satellite clinics compared to all those in the same region who did not (18% versus 6%, p < 0.001). Virologic suppression in 2015 was significantly higher for satellite clinic than non-satellite clinic patients at three of four sites. Care quality indicators were met at a high level at the satellite clinics, comparable to the parent academic clinic. Overall, through community partnerships and WA DOH support, the satellite clinic program increased access to best practice HIV care and improved virologic suppression rates in difficult-to-reach areas. This model could be expanded to other regions with inadequate access to HIV practitioners, though financial support is necessary. [ABSTRACT FROM AUTHOR]

Background Patients who have had a prior myocardial infarction (MI) are at increased risk for adverse outcomes after subsequent percutaneous coronary intervention (PCI). Objective The objective of this study is to examine the efficacy and safety of cangrelor, a potent intravenous P2Y 12 inhibitor, in patients with prior MI. Methods Pooled data from the CHAMPION trials were examined. Prior MI was defined as a history of MI, excluding MI events at baseline. The primary endpoint was a composite of death, MI, ischemia-driven revascularization, or stent thrombosis at 48-h post-randomization. The primary safety endpoint was GUSTO-defined severe bleeding at 48 h. Results Out of 24,691 patients, 5699 (23%) had a prior MI. The primary endpoint was higher in patients with vs. without prior MI (4.9% vs. 4.0%, p = 0.002). The primary endpoint was 4.2% with cangrelor vs. 5.7% with clopidogrel (absolute risk reduction = 1.5%; OR 0.72 [95%CI 0.57–0.92]) in patients with prior MI and 3.7% with cangrelor vs. 4.3% with clopidogrel (absolute risk reduction = 0.6%; OR 0.85 [95%CI 0.74–0.99]) in patients without prior MI ( P -interaction = 0.25). The rate of GUSTO-defined severe bleeding was 0.1% with cangrelor vs. 0.1% with clopidogrel (OR 1.39 [95%CI 0.31–6.24]) in patients with prior MI, and 0.2% with cangrelor vs. 0.2% with clopidogrel (OR 1.18 [95%CI 0.65–2.14]) in patients without prior MI ( P -interaction = 0.84). Conclusion In the CHAMPION trials, patients with prior MI had higher rates of ischemic outcomes within 48 h after PCI. Cangrelor reduced ischemic events with no significant increase in GUSTO-defined severe bleeding in patients with or without prior MI. [ABSTRACT FROM AUTHOR]

The envelope glycoproteins (Envs) of HIV-1 continuously evolve in the host by random mutations and recombination events. The resulting diversity of Env variants circulating in the population and their continuing diversification process limit the efficacy of AIDS vaccines. We examined the historic changes in Env sequence and structural features (measured by integrity of epitopes on the Env trimer) in a geographically defined population in the United States. As expected, many Env features were relatively conserved during the 1980s. From this state, some features diversified whereas others remained conserved across the years. We sought to identify “clues” to predict the observed historic diversification patterns. Comparison of viruses that cocirculate in patients at any given time revealed that each feature of Env (sequence or structural) exists at a defined level of variance. The in-host variance of each feature is highly conserved among individuals but can vary between different HIV-1 clades. We designate this property “volatility” and apply it to model evolution of features as a linear diffusion process that progresses with increasing genetic distance. Volatilities of different features are highly correlated with their divergence in longitudinally monitored patients. Volatilities of features also correlate highly with their population-level diversification. Using volatility indices measured from a small number of patient samples, we accurately predict the population diversity that developed for each feature over the course of 30 years. Amino acid variants that evolved at key antigenic sites are also predicted well. Therefore, small “fluctuations” in feature values measured in isolated patient samples accurately describe their potential for population-level diversification. These tools will likely contribute to the design of population-targeted AIDS vaccines by effectively capturing the diversity of currently circulating strains and addressing properties of variants expected to appear in the future. [ABSTRACT FROM AUTHOR]

Background: Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI).Objectives: This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs).Methods: This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization.Results: Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms.Conclusions: Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571). [ABSTRACT FROM AUTHOR]

Acute medical illnesses are associated with a prolonged elevation in inflammatory markers that predisposes patients to thrombosis beyond the duration of their hospital stay. In parallel, both observational and randomized data have demonstrated a rate of postdischarge venous thromboembolic events that often exceeds that observed in the hospital setting. Despite this significant residual risk of venous thromboembolic events following discharge among acute medically ill patients, no therapeutic strategies have been recommended to address this unmet need. Available randomized trials have demonstrated the efficacy of extending the duration of thromboprophylaxis with available anticoagulants; however, the efficacy is offset, at least in part, by an increase in bleeding events. Identification of the optimal therapeutic strategies, treatment duration, and risk assessment tools that reconcile both efficacy and safety of extended-duration thromboprophylaxis among acute medically ill patients is an area of ongoing investigation. [ABSTRACT FROM AUTHOR]

Objective: The effects of ticagrelor in the subpopulation of patients with ST-elevation myocardial infarction (STEMI) were consistent with those observed in the overall Platelet Inhibition and Patient Outcomes (PLATO) study. However, this subgroup included patients initially or ultimately treated conservatively. The aim of this study is to compare treatment using ticagrelor with treatment using clopidogrel in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).Methods: This post-hoc subgroup analysis compared ticagrelor with clopidogrel in 4949 PLATO patients with STEMI that were treated with primary PCI within 12 h of admission. The primary endpoint was cardiovascular death, myocardial infarction or stroke. The safety endpoint consisted of any major bleeding. Secondary endpoints included stent thrombosis. The analysis was not adequately powered to establish significance of any treatment effects.Results: During a median of 286 days, the primary endpoint occurred in 7.9% of ticagrelor-treated patients versus 8.6% of clopidogrel-treated patients (HR 0.91, 95% CI 0.75 to 1.12, p=0.38). Major bleeding occurred in 6.7% in ticagrelor-treated patients versus 6.8% of clopidogrel-treated patients (HR 0.97, 95% CI 0.77 to 1.22, p=0.79). No interactions were observed for the treatment effect of ticagrelor versus clopidogrel on the primary efficacy (p=0.40) and primary safety endpoints (p=0.15) as compared with the full PLATO population. Treatment with ticagrelor versus clopidogrel reduced the occurrence of definite stent thrombosis (HR 0.58, 95% CI 0.37 to 0.89, p=0.013).Conclusions: In the subset of patients with STEMI treated with primary PCI, ticagrelor compared with clopidogrel was safe, and efficacy outcomes were consistent with the overall PLATO trial.Trial Registration Number: NCT00391872; Results. [ABSTRACT FROM AUTHOR]

The article offers ways in conducting and planning the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial in the U.S. The topics discussed include the primary goal of holding ISCHEMIA trial, the grant proposed to the organization the National Heart, Lung, and Blood Institute (NHLBI), and the estimated number of patients suffering from myocardial infarction.

Objective In the Apixaban for Prevention of Acute Ischemic Events (APPRAISE-2) trial, the use of apixaban, when compared with placebo, in high-risk patients with a recent acute coronary syndrome (ACS) resulted in a significant increase in bleeding without a reduction in ischaemic events. The aim of this analysis was to provide further description of these bleeding events and to determine the baseline characteristics associated with bleeding in high-risk post-ACS patients. Methods APPRAISE-2 was a multinational clinical trial including 7392 high-risk patients with a recent ACS randomised to apixaban (5 mg twice daily) or placebo. Bleeding including Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding, International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding, and any bleeding were analysed using an on-treatment analysis. Kaplan- Meier curves were plotted to describe the timing of bleeding, and a Cox proportional hazards model was used to identify predictors of ISTH major or CRNM bleeding and any bleeding. Median follow-up was 241 days. Results The proportion of patients who experienced TIMI major or minor, ISTH major or CRNM, and any bleeding was 1.5%, 2.2% and 13.3%, respectively. The incidence of bleeding was highest in the immediate post-ACS period (0.11 in the first 30 days vs 0.03 after 30 days events per 1 patient-year); however, >60% of major bleeding events occurred >30 days after the end of the index hospitalisation. Gastrointestinal bleeding was the most common cause of major bleeding, accounting for 45.9% of TIMI major or minor and 39.5% of ISTH major or CRNM bleeding events. Independent predictors of ISTH major or CRNM bleeding events included older age, renal dysfunction, dual oral antiplatelet therapy, smoking history, increased white cell count and coronary revascularisation. Conclusions When compared with placebo, the use of apixaban is associated with an important short-term and long-term risk of bleeding in high-risk post-ACS patients, with gastrointestinal bleeding being the most common source of major bleeding. The baseline predictors of major bleeding appear to be consistent with those identified in lower-risk ACS populations with shorter-term follow-up. Clinical trial No NCT00831441. [ABSTRACT FROM AUTHOR]

Background Many patients receiving oral iron for iron deficiency anemia ( IDA) cannot tolerate or fail to respond to therapy, and existing intravenous ( IV) iron formulations often require repeated administrations. Ferric carboxymaltose ( FCM), a nondextran IV formulation, permits larger single doses. Study Design and Methods We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/ dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C ( FCM as above) or Group D (standard-of-care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper- or hypotensive events. Results Mean (± standard deviation [ SD]) Hb increase was significantly greater in Group A- FCM than Group B-oral iron: 1.57 (±1.19) g/ dL versus 0.80 (±0.80) g/ dL (p = 0.001). Post hoc comparison of Group C- FCM and Group D-IV standard of care also demonstrated significant mean (± SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/ dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups. Conclusion Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response. [ABSTRACT FROM AUTHOR]

The article presents a research study that examined regional variations in the use of in-hospital medical management strategy in non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients with significant coronary artery disease (CAD). Methods employed are described using data from the Early Glycoprotein IIb/IIIa Inhibition in EARLY ACS trial. Results are discussed highlighting global similarities in the profile and prognosis of medically managed NSTE ACS patients.

Background. Patients with iron deficiency anaemia (IDA) in the setting of non-dialysis-dependent chronic kidney disease (NDD-CKD) may benefit from treatment with intravenous (IV) iron. Ferric carboxymaltose (FCM) is a novel IV iron formulation designed to permit larger infusions compared to currently available IV standards such as Venofer® (iron sucrose). [ABSTRACT FROM PUBLISHER]

Objectives: Our purpose was to evaluate long-term mortality and identify factors associated with 1-year mortality in patients who underwent elective percutaneous coronary intervention (PCI). Background: While long-term outcomes in PCI patients have been reported previously, limited data are currently available regarding the comparative long-term outcomes in PCI patients who receive enoxaparin versus intravenous unfractionated heparin (UFH). Methods: We conducted a follow-up analysis of clinical outcomes at 1 year in patients enrolled in the STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous coronary intervention patients, an internationaL randomized Evaluation) trial of 3,528 patients undergoing elective PCI. Patients were randomized to receive either intravenous 0.50-mg/kg or 0.75-mg/kg enoxaparin or intravenous UFH during elective PCI procedures. All-cause mortality at 1 year after index PCI was the main outcome measure. Results: Mortality rates were 1.4%, 2.0%, and 1.5% from 1 month to 1 year, and 2.3%, 2.2%, and 1.9% from randomization to 1 year, after index PCI in patients receiving 0.50 mg/kg enoxaparin, 0.75 mg/kg enoxaparin, and UFH, respectively. Multivariate analysis identified nonfatal myocardial infarction and/or urgent target vessel revascularization up to 30 days after index PCI (hazard ratio: 3.5, 95% confidence interval: 1.7 to 7.3; p < 0.001), and major bleeding within 48 h (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.5; p = 0.04) as the strongest independent risk factors for 1-year mortality. Conclusions: The 1-year mortality rates were low and comparable between patients receiving enoxaparin and UFH during elective PCI. Periprocedural ischemic or bleeding events were the strongest independent predictors of 1-year mortality. (The STEEPLE Trial; NCT00077844) [Copyright &y& Elsevier]

Objective: Limited information exists on the impact of preoperative renal dysfunction on internal thoracic artery and saphenous vein graft failure and 2-year clinical outcomes in patients undergoing coronary artery bypass surgery. Methods: We studied the impact of preoperative renal dysfunction (creatinine clearance < 60 mL/min) on 1-year internal thoracic artery and saphenous vein graft failure (defined as ≥ 75% angiographic stenosis) and 2-year clinical events (death; death or myocardial infarction; and death, myocardial infarction, or revascularization) in 3014 patients undergoing coronary artery bypass surgery enrolled in the Project of Ex-vivo Vein Graft Engineering via Transfection-IV study. Results: Of 2973 patients (98.6%) with preoperative measurement of renal function, 440 (14.8%) had renal dysfunction. Most baseline comorbidities were higher in these patients. Two-year clinical events were higher in patients with preoperative renal dysfunction (adjusted death, myocardial infarction, or revascularization, hazard ratio 1.21, 95% confidence interval 0.97–1.50; adjusted death or myocardial infarction, hazard ratio 1.35, 95% confidence interval 1.05–1.74; adjusted death, hazard ratio 1.47, 95% confidence interval 0.98–2.21). However, saphenous vein graft (odds ratio 1.02, 95% confidence interval 0.79–1.33) and internal thoracic artery (odds ratio 0.76, 95% confidence interval 0.40–1.44) failure were similar in the 2 groups. Conclusion: Although the risk of adverse clinical events is higher in patients with preoperative renal dysfunction, that of internal thoracic artery and saphenous vein graft failure is not. This suggests that factors other than graft failure account for the worse clinical outcomes in this high-risk cohort. Further studies are needed to identify other mechanisms of these worse outcomes so that appropriate measures can be developed to improve long-term outcomes in patients with renal dysfunction undergoing coronary artery bypass surgery. [Copyright &y& Elsevier]

The article presents a study on long-term clinical outcomes after coronary stenting. The study aimed to compare the long-term clinical outcomes of patients receiving drug-eluting stents (DES) and the outcomes of those who were given bare metal stents (BMS). DES and BMS trials indicated a need for target lesion revascularization with no difference in death and myocardial infarction. Patients undergoing initial revascularization with DES and BMS were tested. According to the result, patients receiving DES or BMS have lower target vessel revascularization (TVR) rates.

The article focuses on the acute management of patients presenting with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS), as well as patients with percutaneous coronary intervention (PCI). Different recommendations for patients with NSTE ACS such as immediate aspirin, clopidogrel and upstream treatment, as well as suggestions for antiplatelet and anticoagulant therapies were also discussed.

The article focuses on a study testing the effectiveness and safety of the naturally occurring pyridoxine metabolite and purinergic receptor antagonist MC-1 given to patients undergoing coronary artery bypass graft (CABG) surgery. The objective of the trial was to reduce morbidity and mortality rates in CABG patients due to common complications related to ischemia-reperfusion injury and myocardial infarction (MI). Researchers concluded that MC-1 did not reduce cardiovascular death or nonfatal MI among intermediate to high-risk patients undergoing CABG surgery.

This article presents the second of three physician responses to a hypothetical case in this issue of a 65-year-old diabetic, overweight man who has been diagnosed with coronary heart disease. This physician believes the patient would get a greater benefit from revascularization than he would from medical therapy. The author believes the disease of the left anterior descending coronary artery is most likely responsible for the onset of symptoms and suggests a percutaneous coronary intervention (PCI) be performed with the placement of a drug-eluting stent.

We describe repeated episodes of hepatitis C (HCV) activation associated with initiation of highly active antiretroviral therapy (HAART) in two HIV/HCV coinfected individuals with undetectable serum HCV RNA. Both patients developed high HCV viremia (>1 million IU/mL) and elevations in aminotransferases >10 times upper limit of normal) within 4 months of starting HAART. This is the first report of clinically significant HCV activation in HCV-seropositive patients with initially undetectable HCV viremia. These observations suggest that flares of hepatitis C in the setting of the immune reconstitution inflammatory syndrome can occur even in those patients who have undetectable serum HCV levels prior to HAART initiation. [ABSTRACT FROM AUTHOR]

Background: Increasing number of patients undergo percutaneous intervention of saphenous vein grafts (SVGs). However, the clinical factors associated with long-term mortality after SVG interventions are currently less known. Accordingly, the goal of present study was to evaluate clinical correlates of long-term mortality and to develop a simple bedside tool for risk stratification in patients undergoing SVG interventions. Methods: We analyzed 1019 patients undergoing SVG interventions from the Duke Cardiovascular Disease Database (1986-2003). Cox proportional hazards model was used to identify baseline variables associated with long-term mortality, and the model variables were then used to construct a nomogram for survival probability at 4 years. Results: At a median follow-up of 4 years, 24% of those undergoing SVG interventions died (interquartile range 2-7 years). Independent correlates of death at follow-up on multivariable analysis included presenting heart rate (hazard ratio [HR] 1.02, 95% CI 1.01-1.03), diabetes (HR 1.73, 95% CI 1.37-2.18), presenting heart failure (HR 1.62, 95% CI 1.27-2.06), age (per 10-year increase, HR 1.29, 95% CI 1.13-1.46), peripheral vascular disease (HR 1.59, 95% CI 1.23-2.04), renal insufficiency (HR 2.01, 95% CI 1.36-2.97), patent internal mammary graft (HR 0.67, 95% CI 0.53-0.86), body mass index ≤25 kg/m2 (HR 0.91, 95% CI 0.85-0.97), carotid bruit (HR 1.44, 95% CI 1.12-1.85), S3 ventricular gallop (HR 1.83, 95% CI 1.11-3.03), and hypertension (HR 1.38, 95% CI 1.04-1.83) (c-index 0.83). Bootstrap validation confirmed excellent internal validity of the model (mean c-index 0.84, 95% CI 0.80-0.85). Conclusion: Long-term survival after SVG intervention is poor, with one fourth of patients dying at median follow-up of 4 years. The nomogram developed using the model variables provides a method for clinicians to advise patients undergoing SVG interventions regarding their long-term prognosis, thereby enhancing discharge and long-term follow-up planning and setting up of realistic expectations. [Copyright &y& Elsevier]

In the last decade, a variety of novel anticoagulant and antiplatelet agents that improve outcomes in patients undergoing percutaneous coronary revascularization have emerged. During the next decade, continued refinements in catheter-based device technology should lead to further increases in the number of interventional procedures. The use of optimal antithrombotic strategies is pivotal in reducing adverse events among patients undergoing percutaneous coronary intervention (PCI). Our purpose is to review the current evidence regarding the efficacy of available adjunctive anticoagulant and antiplatelet agents in treating patients undergoing percutaneous coronary revascularization. It should be borne in mind that patients undergoing PCI in the midst of an acute coronary event require a different level of coagulation and platelet aggregation inhibition than low-risk patients undergoing elective PCI for stable angina pectoris. Similarly, generalizing antithrombotic regimen safety data to a wide spectrum of catheter-based therapeutic devices should be avoided. A level of anticoagulation that is safe and effective for angioplasty and stent placement may not be sufficient for devices with longer intracoronary dwell times such as brachytherapy catheters. In light of current evidence, activated clotting times should be targeted in the 200- to 250-second range during elective PCI and in the 250- to 300-second range when intervening on a higher-risk lesion, such as one with an angiographically visible thrombus or in patients presenting with an acute coronary syndrome (ACS). Low-dose enoxaparin sodium is an attractive antithrombin strategy in PCI because it is intrinsically adjusted for renal function, age, and concomitant glycoprotein (GP) IIb/IIIa antagonist use. Other low-molecular weight heparins have also been studied as adjunctive anticoagulants during cardiac catheterization. For example, in pilot studies, dalteparin sodium was shown to have a good safety profile when used alone or in combination with abciximab during PCI. A wealth of data supports the use of a GP IIb/IIIa antagonist in patients presenting with ACS, especially those with high-risk features such as elevated cardiac markers; the systematic use of GP IIb/IIIa inhibitors in this population is therefore encouraged. Overall, the use of GP IIb/IIIa inhibitors reduces the incidence of thrombotic complications following PCI, is associated with a mortality benefit, but has no impact on the risk of restenosis. [ABSTRACT FROM AUTHOR]

Background: The 6-month clinical outcome of patients with multivessel disease enrolled in PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) is described. Patients with complete angiography data were included; multivessel disease was stratified according to the treatment strategy applied early during hospitalization, i.e. medical treatment, percutaneous coronary intervention (PCI) (balloon), PCI (stent), or coronary artery bypass grafting (CABG). Methods: Patients were divided into three groups according to the treatment strategy applied during the first 30 days of enrolment. Patients who did not undergo a percutaneous or surgical coronary intervention were classified as medically treated. Patients who underwent a PCI (prior to a possible CABG) were separated from those who underwent a CABG (prior to a possible PCI). The PCI group was further subdivided: patients receiving ≥1 coronary stents were separated from those in whom no stents were used. Results: The mortality rate at 30 days was 6.7, 3.9, 2.4 and 4.8% for the medical treatment, PCI (balloon), PCI (stent) and CABG groups, respectively (p value = 0.002). Differences as observed at 30 days were still present at 6-month follow-up with 11.1, 5.8, 5.5 and 6.5% mortality event rates for the aforementioned groups (p value = 0.002). The 30-day myocardial infarction (MI) rate according to the opinion of the Clinical Events Committee was lower among medically than non-medically treated patients, with the highest event rate observed in the CABG group (27.7%). Approximately half of the MIs in the PCI and CABG subgroups occurred within 48 h after the procedure. Conclusions: The observed differences in clinical outcomes are explained by an imbalance in baseline characteristics and comorbid conditions between the analyzed groups of patients.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To improve access to high-quality HIV care in underserved regions of Western Washington (WA) State, we collaborated with the WA State Department of Health (DOH) and community partners to launch four satellite HIV clinics. Here, we describe this innovative clinical care model, present an estimate of costs, and evaluate patient care outcomes, including virologic suppression rates. To accomplish this, we assessed virologic suppression rates 12 months before and 12 months after the satellite clinics opened, comparing people living with HIV (PLWH) who enrolled in the satellite clinics versus all PLWH in the same regions who did not. We also determined virologic suppression rates in 2015 comparing satellite clinic versus non-satellite clinic patients and compared care quality indicators between the satellite clinics and the parent academic clinic. Results demonstrate that the change in virologic suppression rate 12 months before to 12 months after the satellite clinics opened was higher for patients who enrolled in the satellite clinics compared to all those in the same region who did not (18% versus 6%, p < 0.001). Virologic suppression in 2015 was significantly higher for satellite clinic than non-satellite clinic patients at three of four sites. Care quality indicators were met at a high level at the satellite clinics, comparable to the parent academic clinic. Overall, through community partnerships and WA DOH support, the satellite clinic program increased access to best practice HIV care and improved virologic suppression rates in difficult-to-reach areas. This model could be expanded to other regions with inadequate access to HIV practitioners, though financial support is necessary. [ABSTRACT FROM AUTHOR]

Background Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss- a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial. Methods and results Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: “26–32 (All)” [lowest level], “20–25”, “15–19”, “1–14”, and “No Teeth” [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively. After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14–1.29), interleukin 6 1.14 (1.10–1.18), lipoprotein-associated phospholipase A 2 activity 1.05 (1.03–1.06), growth differentiation factor 15 1.11 (1.08–1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11–1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98–1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact. Conclusions A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers. Clinical trial registration: www.clinicaltrials.gov ; NCT00799903 . [ABSTRACT FROM AUTHOR]

Background: The Bleeding Academic Research Consortium (BARC) scale has been proposed to standardize bleeding endpoint definitions and reporting in cardiovascular trials. Validation in large cohorts of patients is needed.Objectives: This study sought to investigate the relationship between BARC-classified bleeding and mortality and compared its prognostic value against 2 validated bleeding scales: TIMI (Thrombolysis In Myocardial Infarction) and GUSTO (Global Use of Strategies to Open Occluded Arteries).Methods: We analyzed bleeding in 12,944 patients with acute coronary syndromes without ST-segment elevation, with or without early invasive strategy. The main outcome measure was all-cause death.Results: During follow-up (median: 502 days), noncoronary artery bypass graft (CABG) bleeding occurred in 1,998 (15.4%) patients according to BARC (grades 2, 3, or 5), 484 (3.7%) patients according to TIMI minor/major, and 514 (4.0%) patients according to GUSTO moderate/severe criteria. CABG-related bleeding (BARC 4) occurred in 155 (1.2%) patients. Patients with BARC (2, 3, or 4) bleeding had a significant increase in risk of death versus patients without bleeding (BARC 0 or 1); the hazard was highest in the 30 days after bleeding (hazard ratio: 7.35; 95% confidence interval: 5.59 to 9.68; p < 0.0001) and remained significant up to 1 year. The hazard of mortality increased progressively with non-CABG BARC grades. BARC 4 bleeds were significantly associated with mortality within 30 days (hazard ratio: 10.05; 95% confidence interval: 5.41 to 18.69; p < 0.0001), but not thereafter. Inclusion of BARC (2, 3, or 4) bleeding in the 1-year mortality model with baseline characteristics improved it to an extent comparable to TIMI minor/major and GUSTO moderate/severe bleeding.Conclusions: In patients with acute coronary syndromes without ST-segment elevation, bleeding assessed with the BARC scale was significantly associated with risk of subsequent death up to 1 year after the event and risk of mortality increased gradually with higher BARC grades. Our results support adoption of the BARC bleeding scale in ACS clinical trials. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER] [Study P04736]; NCT00527943). [ABSTRACT FROM AUTHOR]

Background The relationship between culprit vessel, infarct size, and outcomes in non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear. In some reports, the left circumflex artery (LCX) was more often the culprit at angiography than the right coronary artery (RCA) or left anterior descending artery (LAD), and infarcts were larger with LCX culprits. Methods We determined culprit vessel frequency and initial patency (TIMI flow grade), median fold elevation of peak troponin above the upper limit of normal, and outcomes (30-day death or myocardial infarction [MI] and 1-year mortality) by culprit vessel in high-risk NSTE ACS patients in the EARLY ACS trial. Results Of 9406 patients, 2066 (22.0%) had angiographic core laboratory data. We evaluated 1774 patients for whom the culprit artery was not the left main, a bypass graft, or branch vessel. The culprit was the LCX in 560 (31.6%), LAD in 653 (36.8%), and RCA in 561 (31.6%) patients. There were fewer women (24.1%) and more prior MI (25.5%) among patients with a culprit LCX compared with those with a culprit LAD or RCA. Patients with LCX (21.2%) and RCA (27.5%) culprits more often had an occluded artery (TIMI 0/1) than did those with LAD (11.3%). Peak troponin elevation was significantly higher for LCX than RCA or LAD culprits. LCX culprit vessels were not associated with worse 30-day or 1-year outcomes in adjusted models. Conclusions Among patients with NSTE ACS, the frequencies of LCX, LAD, and RCA culprits were similar. Although LCX lesions were associated with higher peak troponin levels, there was no difference in short- or intermediate-term outcomes by culprit artery. [ABSTRACT FROM AUTHOR]

All patients with stable ischemic heart disease (SIHD) should be managed with guideline-directed medical therapy (GDMT), which reduces progression of atherosclerosis and prevents coronary thrombosis. Revascularization is also indicated in patients with SIHD and progressive or refractory symptoms, despite medical management. Whether a strategy of routine revascularization (with percutaneous coronary intervention or coronary artery bypass graft surgery as appropriate) plus GDMT reduces rates of death or myocardial infarction, or improves quality of life compared to an initial approach of GDMT alone in patients with substantial ischemia is uncertain. Opinions run strongly on both sides, and evidence may be used to support either approach. Careful review of the data demonstrates the limitations of our current knowledge, resulting in a state of community equipoise. The ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) is being performed to determine the optimal approach to managing patients with SIHD, moderate-to-severe ischemia, and symptoms that can be controlled medically. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522). [ABSTRACT FROM AUTHOR]

Objectives: This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background: In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). Methods: A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, excluded silent MI. Results: Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). Conclusions: In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872) [Copyright &y& Elsevier]

Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial compared vorapaxar and placebo in 12,944 high-risk patients with none ST-segment elevation acute coronary syndrome. We explored aspirin (ASA) use and its association with outcomes. Kaplan-Meier event rates were compared in groups defined by ASA dose (low, medium, and high). Landmark analyses with covariate adjustment were performed for 0 to 30, 31 to 180, and 181 to 365 days. Of 12,515 participants, 7,523, 1,049, and 3,943 participants were treated with low-, medium-, and high-dose ASA at baseline, respectively. Participants enrolled in North America versus elsewhere were more often treated with a high dose at baseline (66% vs 19%) and discharge (60% vs 3%). Unadjusted cardiovascular death, myocardial infarction, stroke, hospitalization for ischemia, or urgent revascularization event rates tended to be higher with higher baseline ASA (18.45% low, 19.13% medium, and 20.27% high; p for trend [ 0.15573). Unadjusted and adjusted hazard ratios (95% confidence intervals) for effect of vorapaxar on cardiovascular (unadjusted p for interaction [ 0.065; adjusted p for interaction [ 0.140) and bleeding (unadjusted p for interaction [ 0.915; adjusted p for interaction[ 0.954) outcomes were similar across groups. Landmark analyses showed similar safety and efficacy outcomes with vorapaxar and placebo by ASA dose at each time point except for 0 to 30 days, when vorapaxar tended to be worse for efficacy (hazard ratio 1.13, 95% confidence interval 0.89 to 1.44, p for interaction [ 0.0157). In conclusion, most TRACER participants were treated with low-dose ASA, although a high dose was common in North America. High-dose participants tended to have higher rates of ischemic and bleeding outcomes. Although formal statistical testing did not reveal heterogeneity in vorapaxar’s effect across dose subgroups, consistent trends support use of low-dose ASA with other antiplatelet therapies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Data are limited on whether clinical trials have randomized higher-risk patients over time and how trends in risk profiles and evidence-based pharmacotherapies have influenced trial outcomes. We quantified changes in baseline risk, treatment, and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) randomized in 9 phase 3 clinical trials of antithrombotic therapy over 15years. Methods: We studied 58,771 patients in GUSTO IIb, PURSUIT, PARAGON-A, PARAGON-B, PRISM, PRISM-PLUS, GUSTO IV-ACS, SYNERGY, and EARLY ACS. Patient-level data were mapped to 3 pre-specified 5-year randomization periods. Temporal trends in GRACE score-predicted mortality were compared with trends in observed mortality. Results: Over time, in-hospital and discharge use of thienopyridines (p=0.001), statins (p<0.0001), and angiotensin-converting enzyme inhibitors (p<0.0001) increased, and hospital length-of-stay decreased (p=0.024). Blood transfusion use increased (8.3% [1994–98], 10.7% [1999–2003], 13% [2004–08], p=0.0002) despite stable rates of severe bleeding (0.9% [1994–98], 1.4% [1999–2003] and 1.1% [2004–08], p=0.127) and coronary artery bypass grafting (12.4% [1994–98], 13.7% [1999–2003] 13.1% [2004–08], p=0.880). Although predicted 6-month mortality increased (6.9% [1994–98], 9.0% [1999–2003], 7.9% [2004–08], p=0.017), observed 6-month mortality decreased (6.7% [1994–98], 5.8% [1999–2003], 5.1% [2004–08], p=0.025). Thirty-day myocardial infarction rates remained stable (9.2% [1994–98], 9.3% [1999–2003], 10% [2004–08], p=0.539). Conclusions: Despite enrolling higher-risk patients into these NSTE ACS trials, with better treatment, observed mortality declined over the past 15years. The appropriateness of increased blood transfusion despite unchanged bleeding rates deserves further study. [Copyright &y& Elsevier]

Objectives: The purpose of this study is to evaluate the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery (CABG), as a post-randomization strategy. Background: Ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y12-receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes, ticagrelor compared with clopidogrel significantly reduced the risk of the primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.77 to 0.92; p < 0.001). This report investigated the outcomes of patients treated with CABG during the trial. Methods: In total, 1,899 patients underwent CABG post-randomization. The protocol recommended ticagrelor/placebo to be withheld for 24 to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients underwent CABG and were receiving study drug treatment <7 days before surgery. The statistical analysis was based on events occurring from the CABG procedure until the end of the study, excluding 3 patients with CABG after study end. Results: In the 1,261 patient cohort, the relative reduction of primary composite end point at 12 months (10.6% [66 of 629] with ticagrelor versus 13.1% [79 of 629] with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent with the results of the whole trial. Total mortality was reduced from 9.7% (58 of 629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from 7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01), and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no significant difference in CABG-related major bleeding between the randomized treatments. Conclusions: In the subgroup of patients undergoing CABG within 7 days after the last study drug intake, ticagrelor compared with clopidogrel was associated with a substantial reduction in total and CV mortality without excess risk of CABG-related bleeding. [Copyright &y& Elsevier]

Antithrombotic agents are an integral component of the medical regimens and interventional strategies currently recommended to reduce thrombotic complications in patients with acute coronary syndromes (ACS). Despite great advances with these therapies, associated high risks for thrombosis and hemorrhage remain as the result of complex interactions involving patient comorbidities, drug combinations, multifaceted dosing adjustments, and the intricacies of the care environment. As such, the optimal combinations of antithrombotic therapies, their timing, and appropriate targeted subgroups remain the focus of intense research. During the last several years a number of new antithrombotic treatments have been introduced, and new data regarding established therapies have come to light. Although treatment guidelines include the most current available data, subsequent findings can be challenging to integrate. This challenge is compounded by the complexity associated with different efficacy and safety measures and the variability in study populations, presenting syndromes, physician, and patient preferences. In this work we review recent data regarding clinically available antiplatelet and anticoagulation agents used in the treatment of patients with ACS. We address issues including relative efficacy, safety, and timing of therapies with respect to conservative and invasive treatment strategies. In specific cases we will highlight remaining questions and controversies and ongoing trials, which will hopefully shed light in these areas. In addition to reviewing existing agents, we take a look forward at the most promising new antithrombotics currently in late-stage clinical development and their potential role in the context of ACS management. [Copyright &y& Elsevier]

: ObjectivesWe sought to determine whether income-based disparities in care processes and outcome exist in patients with acute coronary syndromes.: BackgroundUsing income proxies and limited clinical data, some observational studies have shown income disparities in outcome after acute myocardial infarction (MI).: MethodsUsing annual household income from the economic substudy of the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, patients were grouped into low-, middle-, and high-income categories based on the U.S. Census Bureau definition of poverty. Logistic regression analysis was used to examine the association between income category and the use of cardiac procedures and the prescription of evidence-based medications at hospital discharge. Cox regression analysis was used to examine the hazard of 30-day and six-month death or recurrent MI across income categories, after adjusting for baseline characteristics.: ResultsLow-income patients had more chronic medical conditions and were sicker at presentation. Among low-income patients, the use of some evidence-based medications and cardiac procedures was lower and the unadjusted rates of 30-day death and six-month death or MI was higher. After multivariable adjustment, there was no consistent pattern for disparity in care processes, but the trend for higher short and intermediate-term death or MI persisted for low-income patients.: ConclusionsIncome level is associated with a trend toward worse outcome among patients with acute coronary syndromes. The disparity in 30-day and six-month death or MI between low and high-income patients could not be readily explained by differences in in-hospital medical or invasive treatment, suggesting that the poor outcomes may be due to differences occurring after hospital discharge. [Copyright &y& Elsevier]

Background: Anemia is a common finding and independent predictor for adverse outcomes in hospitalized patients with medical illness. It remains unclear whether anemia is a risk factor for venous thromboembolism and whether the presence of anemia can refine risk assessment for prediction of venous thromboembolism, thereby adding incremental utility to a validated model.Methods: In the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban trial (APEX), 7513 hospitalized medical patients were randomized to receive either betrixaban or standard-of-care enoxaparin for thromboprophylaxis. Baseline hemoglobin concentrations were obtained in 6861 patients, with a follow-up of 77 days. Symptomatic venous thromboembolism events, including symptomatic deep vein thrombosis, pulmonary embolism, and venous thromboembolism-related mortality, were compared between low-hemoglobin and normal-hemoglobin groups (normal range: 12.5-17.0 g/dL for males and 11.0-15.5 g/dL for females). The relationship between anemia and venous thromboembolism events was assessed by fitting a univariable and multivariable logistic regression model composed of thromboprophylaxis and risk factors. Venous thromboembolism risk refinement by hemoglobin measurement was evaluated in the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) risk assessment model.Results: Low hemoglobin at baseline was associated with a greater risk of symptomatic venous thromboembolism (relative risk [RR] 1.94 [95% confidence interval, 1.27-2.98]; P = .002), symptomatic deep vein thrombosis (RR 2.29 [1.12-4.68]; P = .019), and nonfatal pulmonary embolism (RR 2.63 [1.22-5.65]; P = .010) but not venous thromboembolism-related mortality (RR 1.47 [0.71-3.04]; P = .30). After adjusting for thromboprophylaxis, history of previous venous thromboembolism, intensive or coronary unit admission, and D-dimer, low hemoglobin (as a categorical or continuous variable) remained associated with an increased likelihood of venous thromboembolism (adjusted odds ratio 1.71 [95% confidence interval, 1.09-2.69]; P = .020). Low hemoglobin also improved risk discrimination and reclassification after inclusion in the IMPROVE model.Conclusions: Anemia was independently associated with a greater risk of symptomatic venous thromboembolism among acutely ill medical patients despite the provision of thromboprophylaxis. Hemoglobin measurement also improved risk stratification by the IMPROVE venous thromboembolism risk score. [ABSTRACT FROM AUTHOR]