Effectiveness and safety of Dabigatran 110 mg versus 150 mg for Stroke Prevention in Patients with Atrial Fibrillation at High Bleeding Risk

PurposeThe effectiveness and tolerability of a reduced dose (110 mg) of dabigatran versus the standard dose (150 mg) were evaluated in subgroups of patients with atrial fibrillation (AF) at high bleeding risk.MethodsEligible patients were adults with AF and a creatinine clearance rate ≥30 mL/min who were initiated on treatment with dabigatran (index) between 2016 and 2018. High–bleeding-risk subgroups were identified: (1) age ≥80 years; (2) moderate renal impairment (creatinine clearance rate 30–<50 mL/min); and (3) recent bleeding or a HAS-BLED score of ≥3. Fine-Gray subdistribution hazard regression models with inverse probability of treatment weights were used to investigate associations between dabigatran dose and three outcomes: stroke or systemic embolism, major bleeding requiring hospitalization, and all-cause mortality.FindingsAmong 7858 patients with AF and a high bleeding risk (age ≥80 years, 3472; moderate renal impairment, 1574; recent bleeding or HAS-BLED score ≥3, 2812), 32.3% received reduced-dose dabigatran. Compared with the standard dose, use of the reduced dose of dabigatran was not associated with an increased risk for stroke or systemic embolism but was associated with a lower risk for major bleeding (HR = 0.65; 95% CI, 0.44–0.95) and all-cause mortality (HR = 0.78; 95% CI, 0.65–0.92) in patients aged ≥80 years. The use of reduced-dose dabigatran was associated with a lower risk for major bleeding (HR = 0.54; 95% CI, 0.30–0.95) and all-cause mortality among patients with moderate renal impairment (HR = 0.53; 95% CI, 0.40–0.71).ImplicationsLower risks for bleed and mortality associated with reduced- versus standard-dose dabigatran in patients with AF and a high bleeding risk suggest a better dosing strategy.     

≥75岁急诊心房颤动患者的预后分析——中国急诊心房颤动研究的亚组分析

目的:了解老年（年龄≥75岁）急诊心房颤动（房颤）患者的预后情况,分析不良预后的危险因素。方法:2009年至2011年在全国20家医院连续入选急诊就诊、年龄≥75岁房颤患者为本研究对象,收集患者基线资料和治疗情况,并进行1年随访,主要终点事件为全因死亡,次要终点事件为心血管死亡、卒中、大出血事件及主要不良事件。应用单因素和多因素Cox回归模型分析上述事件的独立危险因素。结果:共入选766例老年急诊房颤患者,年龄(80.76±4.66)岁,女性占56.9%。1年的全因病死率为24.3%,心血管病死率为12.8%,卒中发生率为10.6%,主要不良事件发生率33.6%,再入院率32%。多因素Cox回归模型分析显示年龄（ HR1.073,95% CI 1.042~1.105）、心率（ HR 1.008,95% CI 1.002~1.013）、痴呆/认知障碍史（ HR 1.849,95% CI 1.016~3.365）、既往慢性阻塞性肺疾病史（ HR 1.824,95% CI 1.303~2.551）为老年房颤患者1年死亡的独立危险因素。女性（ HR 1.664,95% CI 1.036~2.675）、高血压病史（ HR 2.035,95% CI 1.080~3.836）、痴呆/认知障碍史（ HR 2.773,95% CI 1.220~6.302）、为老年房颤患者1年卒中的独立危险因素。 结论:老年急诊房颤患者的预后较差,年龄、心率、痴呆/认知障碍史、慢性阻塞性肺疾病史是老年急诊房颤患者1年全因死亡和主要不良事件的独立危险因素;女性、高血压病史、痴呆/认知障碍史为老年急诊房颤患者1年卒中的独立危险因素。     

Prognostic value of GRACE and CHA2DS2-VASc score among patients with atrial fibrillation undergoing percutaneous coronary intervention

AimsThe GRACE and CHA2DS2-VASc risk score are developed for risk stratification in patients with acute coronary syndrome and AF, respectively. We aimed to assess the predictive performance of the GRACE score and CHA2DS2-VASc score among patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).MethodsConsecutive patients with a diagnosis of AF admitted to our hospital for PCI between January 2016 and December 2018 were included and followed up for at least 1 year. The primary endpoint was a composite of major adverse cardiac events (MACEs) including all-cause mortality, repeat revascularization, myocardial infarction, or ischaemic stroke.ResultsA total of 1452 patients were identified. Cox regression demonstrated that the GRACE (HR 1.014, 95% CI 1.008–1.020, p < 0.001) but not the CHA2DS2-VASc score was associated with the risk of MACEs. Both GRACE and CHA2DS2-VASc scores were predictive of all-cause mortality with HR of 1.028 (95% CI 1.020–1.037, p < 0.001) and 1.334 (95% CI 1.107–1.632, p = 0.003). Receiver operating characteristic analyses showed both scores had similar discrimination capacity for all-cause mortality (C-statistic: 0.708 for GRACE vs. 0.661 for CHA2DS2-VASc, p = 0.299). High GRACE score was also significantly associated with increased risk of ischaemic stroke (HR 1.018, 95% CI 1.005–1.031, p = 0.006) and major bleeding (HR 1.012, 95% CI 1.001–1.024, p = 0.039), whereas high CHA2DS2-VASc score was not.ConclusionsHigh GRACE score but not CHA2DS2-VASc score were both associated with an increased risk of MACEs after PCI in patients with AF. The GRACE and CHA2DS2-VASc scores have similar predictive performance for predicting all-cause mortality.

Key messages:

• In patients with AF undergoing PCI, increasing GRACE but not CHA2DS2-VASc scores was independently associated high risk of MACEs.
• The GRACE score could also help identify patients at higher risk of stroke and major bleeding.
• Both GRACE and CHA2DS2-VASc scores showed good ability in the prediction of all-cause mortality.

     

d-dimer predicts major bleeding,cardiovascular events and all-cause mortality during warfarin treatment

ObjectivesPrevious studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of d-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.Design and methodsIn a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for d-dimer, tPA, and tPA/PAI-1 complex.ResultsIn multivariate Cox regression analysis, high levels of d-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01–1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05–1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06–1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.ConclusionWe conclude that high levels of d-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment.     

Overweight is associated with improved survival and outcomes in patients with atrial fibrillation

Background

The aim of this study was to investigate the association of body mass index (BMI) with mortality and cardiovascular events in Chinese patients with atrial fibrillation (AF).

Methods and results

This study consecutively enrolled AF patients presenting to an emergency department at 20 hospitals in China from November 2008 to October 2011. A total of 2,016 AF patients was enrolled, and patients were categorized as underweight (BMI <18.5), normal (BMI 18.5 to <24), overweight (BMI 24 to <28), and obese (BMI ≥28 all kg/m²). Multivariate Cox proportional hazards regression was used on all the patients. End points of the analyses were all-cause mortality, cardiovascular mortality, and combined end events. Among overall patients, mean BMI was 23.5 ± 3.6 kg/m²; 279 (13.8 %) patients died during 12-month follow-up, and so did 23.2 % underweight, 16.3, 9.5 and 9.2 % normal weight, overweight, and obese patients, respectively (P < 0.001). Cardiovascular mortality was 8.3% in all patients, and in underweight, normal weight, overweight and obese categories were 16.5, 9.0, 5.4 and 6.9 %, respectively (P < 0.001). On multivariate analysis, as continuous variable, BMI was not a risk factor for all-cause mortality in AF patients (hazard ratio [HR] 0.94; 95 % confidence interval [CI] 0.91–0.97; P = 0.001). As categorical variable, underweight (HR 1.57, 95 % CI 1.02–2.42, P = 0.041) and normal weight (HR 1.53, 95 % CI 1.13–2.06, P = 0.005) categories were associated with higher all-cause mortality as compared with overweight category. Underweight (HR 2.01, 95 % CI 1.76–3.43, P = 0.011) and normal weight patients (HR 1.53, 95 % CI 1.03–2.28, P = 0.037) also had higher cardiovascular mortality as compared with the overweight category.

Conclusions

Obesity and overweight were not risk factors for 12-month mortality in Chinese AF patients. Overweight AF patients have better survival and outcomes than normal weight (BMI 18.5–24 kg/m²) and underweight patients.     

Prognostic value of red blood cell distribution width for mortality in patients with hypertrophic cardiomyopathy

BackgroundRed blood cell distribution width (RDW) has emerged as a useful indicator for adverse outcomes in several cardiovascular diseases. The relation between RDW and the prognosis of hypertrophic cardiomyopathy (HCM) remains to be evaluated. We examined the relation between RDW and all-cause mortality and HCM-related death in a population of adult HCM patients.MethodsWe performed clinical evaluation in 414 consecutive adult HCM patients (median age, 57.5 years; male, 54.8%).ResultsDuring a median follow-up of 3.7 years, all-cause mortality and HCM-related death occurred in 75 (18.1%) and 50 (12.1%) patients, respectively. Based on the tertiles of baseline RDW, mortality increased with higher tertile. With the tertile 1 as reference, adjusted all-cause mortality hazard ratios (HRs) were 3.9 for the tertile 2 (95% confidence interval [CI]: 1.5–10.3) and 3.1 for the tertile 3 (95% CI: 1.1–8.2). Adjusted HCM-related death HRs were higher in the tertile 2 (HR: 5.5; 95% CI: 1.2–24.4) and tertile 3 (HR: 6.6; 95% CI: 1.5–29.0) compared with the tertile 1. Further smooth curve fitting exhibited a saturation effect after adjusting for confounders, and there were a two-stage change and an inflection point. Two-piecewise Cox model suggested mortality significantly increased with RDW level up to the inflection point (about 14.0% for both all-cause mortality and HCM-related death), and RDW was not associated with mortality after the point.ConclusionIn adult HCM patients, we found increased RDW was a significant risk predictor for all-cause mortality and HCM-related death, and a saturation effect was observed.     

Failure of vital sign normalization is more strongly associated than single measures with mortality and outcomes

BackgroundModified Early Warning Systems (MEWS) scores offer proxies for morbidity and mortality that are easily acquired, but there are limited data on what changing MEWS scores within the ED indicate. We examined the correlation of changing MEWS scores during resuscitation in the ED and in-hospital morbidity and mortality.MethodsWe conducted a retrospective analysis on medical ED patients with simplified MEWS scores (without urine output or mental status) admitted to a single academic tertiary care center over one year. Triage-to-Last delta MEWS score and Triage-to-Max delta MEWS scores were calculated and correlated to in-hospital mortality, ICU admission, length of stay (LOS) and diagnosis of sepsis.ResultsOur analysis included 8322 ED patients with an ICU admission rate of 17% and a mortality rate of 2%. Every point of worsened MEWS after triage was more strongly associated with all-cause mortality (OR 2.41, 95% CI 1.96–2.97) than triage MEWS alone (OR 1.33, 95% CI 1.23–1.44; p < 0.001). Likewise, each point of worsened MEWS was associated with increased odds of ICU admission (Triage-to-Last: OR 2.12, 95% CI 1.92–2.33 and Triage-to-Max: OR 1.52, 95% CI 1.45–1.60, respectively). Among patients with suspected infection, similar associations are found.ConclusionsDynamic vital signs in the emergency department, as categorized by delta MEWS, and failure to normalize abnormalities, were associated with increased mortality, ICU admission, LOS, and the diagnosis of sepsis. Our results suggest that MEWS scores that do not normalize, from triage onward, are more strongly associated with outcome than any single score.     

On-admission anemia predicts mortality in COVID-19 patients: A single center,retrospective cohort study

ObjectivesWe investigated the impact of anemia based on admission hemoglobin (Hb) level as a prognostic risk factor for severe outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19).MethodsA single-center, retrospective cohort study was conducted from a random sample of 733 adult patients (age ≥ 18 years) obtained from a total of 4356 laboratory confirmed SARS-CoV-2 cases who presented to the Emergency Department of Montefiore Medical Center between March–June 2020. The primary outcome was a composite endpoint of in-hospital severe outcomes of COVID-19. A secondary outcome was in-hospital all-cause mortality.ResultsAmong the 733 patients included in our final analysis, 438 patients (59.8%) presented with anemia. 105 patients (14.3%) had mild, and 333 patients (45.5%) had moderate-severe anemia. Overall, 437 patients (59.6%) had a composite endpoint of severe outcomes. On-admission anemia was an independent risk factor for all-cause mortality, (Odds Ratio 1.52, 95% CI [1.01–2.30], p = 0.046) but not for composite severe outcomes. However, moderate-severe anemia (Hb < 11 g/dL) on admission was independently associated with both severe outcomes (OR1.53, 95% CI [1.05–2.23], p = 0.028) and mortality (OR 1.67, 95% CI [1.09–2.56], p = 0.019) during hospitalization.ConclusionAnemia on admission was independently associated with increased odds of all-cause mortality in patients hospitalized with COVID-19. Furthermore, moderate-severe anemia (Hb <11 g/dL) was an independent risk factor for severe COVID-19 outcomes. Moving forward, COVID-19 patient management and risk stratification may benefit from addressing anemia on admission.     

Predictors of digoxin use and risk of mortality in ED patients with atrial fibrillation

Objectives

The aim of this study was to evaluate factors of digoxin use and its relation to mortality in ED patients with atrial fibrillation (AF).

Depression or anxiety and all-cause mortality in adults with atrial fibrillation – A cohort study in Swedish primary care

Objective Our aim was to study depression and anxiety in atrial fibrillation (AF) patients as risk factors for all-cause mortality in a primary care setting.

Methods The study population included adults (n?=?12?283) of 45 years and older diagnosed with AF in 75 primary care centres in Sweden. The association between depression or anxiety and all-cause mortality was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses were conducted in men and women, adjusted for age, educational level, marital status, neighborhood socio-economic status (SES), change of neighborhood status and anxiety or depression, respectively, and cardiovascular co-morbidities. As a secondary analysis, background factors and their association with depression or anxiety were explored.

Results The risk of all-cause mortality was higher among men with depression compared to their counterparts without depression even after full adjustment (HR?=?1.28, 95% CI 1.08–1.53). For anxiety among men and anxiety or depression among women with AF, no associations were found. Cerebrovascular disease was more common among depressed AF patients.

Conclusions Increased awareness of the higher mortality among men with AF and subsequent depression is called for. We suggest a tight follow-up and treatment of both ailments in clinical practice.     

Predictive value of the National Early Warning Score–Lactate for mortality and the need for critical care among general emergency department patients

Study objectivesWhat is the predictive value of the National Early Warning Score–Lactate (NEWS-L) score for mortality and the need for critical care in general emergency department (ED) patients?MethodsIn this retrospective cohort study, we enrolled all adult patients who visited the ED of an urban academic tertiary-care university hospital in South Korea over 2 consecutive months. The primary outcome was 2-day mortality. The secondary outcomes were the need for critical care (advanced airway use, vasopressor or inotropic agent use, intensive care unit admission) during an ED stay; 2-day composite outcome (2-day mortality and the need for critical care); 7-day mortality; and in-hospital mortality.ResultsDuring the study period, 4624 adult patients visited the ED. Of these, 87 (1.9%) died within 2 days. In total, 481 patients (10.4%) required critical care during their ED stay. The 2-day composite outcome, 7-day mortality, and in-hospital mortality were 10.9% (503/4624), 2.5% (116/4624), and 3.9% (182/4624), respectively. The NEWS-L demonstrated excellent predictive value for 2-day mortality with an area under the receiver operating characteristic curve (AUROC) of 0.96 (95% confidence interval [CI], 0.94-0.98); this value was better than that of the NEWS alone (AUROC 0.94 [95% CI, 0.91-0.96], P = .002). The AUROC of the NEWS-L for the need for critical care was 0.83 (95% CI, 0.81-0.85); for the 2-day composite outcome, it was 0.84 (95% CI, 0.82-0.86); for 7-day mortality, it was 0.94 (95% CI, 0.92-0.96); and for in-hospital mortality, it was 0.87 (95% CI, 0.85-0.90). Logistic regression results confirmed that the ratio of the NEWS to the initial lactate level was 1:1. Similar results were obtained in the subgroup analyses (disease-infection, disease–vascular and heart, disease-others, and nondisease). The high-risk NEWS-L group (NEWS-L ≥ 7, 9.4% of all patients) had an adjusted odds ratio of 28.67 (12.66-64.92) for 2-day mortality in the logistic regression model adjusted for basic characteristics.ConclusionThe NEWS-L can provide excellent discriminant value for predicting 2-day mortality in general ED patients, and it has the best discriminant value regarding the need for critical care and composite outcomes. The NEWS-L may be helpful in the early identification of at-risk general ED patients.     

Osteoporosis and Its Association With Cardiovascular Disease,Respiratory Disease,and Cancer: Findings From the UK Biobank Prospective Cohort Study

ObjectiveTo investigate sex-specific associations of osteoporosis with incidence of and mortality from cardiovascular disease (CVD), respiratory disease, and cancer as well as with all-cause mortality.MethodsIn total, 305,072 participants (53% [161,383] women) of UK Biobank were included in this study (2007-2010). Self-reported diagnosis of osteoporosis at baseline was the exposure of interest. The outcomes were CVD, respiratory disease, chronic obstructive pulmonary disease (COPD), all cancer, and prostate and breast cancer incidence and mortality and all-cause mortality. Associations between osteoporosis and outcomes were investigated using Cox proportional hazards models.ResultsIn men, osteoporosis was associated with a higher incident risk of all respiratory diseases (hazard ratio [HR], 1.26; 95% CI, 1.06 to 1.50) including COPD (HR, 1.82; 95% CI, 1.38 to 2.40). Men with osteoporosis also had a higher mortality risk from all causes (HR, 1.71; 95% CI, 1.38 to 2.11), CVD (HR, 1.68; 95% CI, 1.19 to 2.37), respiratory disease (HR, 2.35; 95% CI, 1.70 to 3.24), and COPD (HR, 3.64; 95% CI, 2.24 to 5.91). These associations persisted after adjustment for age, body mass index, and comorbidities. Women with osteoporosis had a higher risk of incident CVD (HR, 1.24; 95% CI, 1.97 to 1.44), respiratory disease (HR, 1.23; 95% CI, 1.13 to 1.33), and COPD (HR, 1.29; 95% CI, 1.10 to 1.52). Women with osteoporosis also had a higher mortality risk from respiratory disease (HR, 1.31; 95% CI, 1.00 to 1.72) and breast cancer (HR, 1.60; 95% CI, 1.14 to 2.26).ConclusionCompared with women, men with osteoporosis had a higher risk of all-cause mortality, mortality from respiratory diseases including COPD, and cancer incidence. Osteoporosis was strongly associated with respiratory disease and COPD in both sexes, even after full adjustment for covariates, although men with osteoporosis experienced a higher risk of adverse outcomes.     

Efficacy and safety of traditional Chinese medicine on thromboembolic events in patients with atrial fibrillation: A systematic review and meta-analysis

ObjectivesTraditional Chinese medicine (TCM) in combination with Western medicine (WM) has been widely used worldwide. This systematic review aimed to evaluate the efficacy and safety of TCM in prevention of thromboembolic events in patients with atrial fibrillation (AF).MethodsPotential studies were searched through the Cochrane Library, PubMed, EMBASE, CBM, VIP, CNKI, and Wanfang databases up to February 2016. Randomized controlled trials (RCTs) investigating the thromboembolic events and/or safety outcome of TCM in patients with AF were included.ResultsA total of 905 AF patients from 9 RCTs were identified. Meta-analysis showed that TCM in combination with warfarin was better than warfarin alone for preventing total thromboembolic events with a 68% reduction of risk (risk ratio [RR] 0.32; 95% confidence interval [CI] 0.13–0.78) without increasing the risk of total bleeding (RR 0.71; 95% CI 0.29–1.72). Compared with warfarin, TCM therapy was associated with lower risk of total bleeding (RR 0.13; 95% CI 0.04–0.47), but increased the risk of total thromboembolic events (RR 1.84; 95% CI 1.03–3.27).ConclusionsThis meta-analysis suggests that TCM combined with warfarin is superior to warfarin alone for the prevention of total thromboembolic events in patients with AF, with equal risk of bleeding as warfarin alone.     

Risk stratification of patients with atrial fibrillation in the emergency department

Introduction and methodsEarly and accurate risk stratification of patients with atrial fibrillation (AF) in the emergency department (ED) could aid the physician in determining a timely treatment strategy appropriate to the severity of disease. We conducted a retrospective review of 243 adult patients who presented to a tertiary ED with AF in 2017. Primary outcome studied was 30-day adverse event (a composite outcome of repeat visit to the ED, cardiovascular complications, and all-cause mortality).Secondary outcome studied was 90-day all-cause mortality. We compared the performance of the RED-AF, AFTER and CHA2DS2-VASc score by plotting receiver operating characteristic (ROC) curves and estimating the areas under curves (AUC), and assessed the potential to further improve the tools with their incorporation of new variables.ResultsExisting scoring tools had poor predictive value for 30-day adverse events, with the RED-AF score performing comparatively better, followed by the AFTER and CHA2DS2-VASc score. All scores performed collectively better to predict 90-day mortality, with the AFTER score performing the best, followed by the RED-AF and CHA2DS2-VASc score. By incorporating heart rate at initial presentation to the ED as a variable into the AFTER Score, we generated a Modified AFTER Score with superior predictive performance above existing scores for 90-day mortality.ConclusionExisting scores collectively performed poorly to predict 30-day adverse outcomes, but the AFTER and Modified AFTER score showed good predictive value for 90-day mortality. Further studies should be done to validate their use in guiding clinician’s disposition of patients with AF in the ED.     

Revascularization in Patients With Non-ST Elevation Myocardial Infarction and Advanced Chronic Kidney Disease

ObjectiveTo investigate the impact of revascularization on long-term survival and renal outcome in non–ST-elevation myocardial infarction (NSTEMI) patients with severe chronic kidney disease (CKD).Patients and MethodsThis study includes NSTEMI patients with an estimated glomerular filtration rate <30 mL/min per 1.73 m², including those on chronic hemodialysis who were identified from the multicenter Chang Gung Research Database from January 1, 2007, to December 31, 2017. Inverse probability of treatment weighting was used to generate comparable groups. The survival and the risk of progression to chronic hemodialysis between those receiving revascularization, either percutaneous coronary intervention or coronary artery bypass graft, and those receiving medical therapy during index hospitalization were compared.ResultsA total of 2821 NSTEMI patients with severe CKD, including 1141 patients on chronic hemodialysis, were identified. Of these, 1149 patients received revascularization and 1672 received medical therapies. The differences in demographics, comorbidities, and presentations between groups were balanced after inverse probability of treatment weighting. After a mean follow-up of 1.82 years, revascularization was associated with a lower risk of all-cause mortality (adjusted HR, 0.61; 95% CI, 0.54-0.70). For non–dialysis-dependent patients who had survival to discharge, revascularization had a higher risk of progression to chronic hemodialysis (adjusted HR, 1.83; 95% CI, 1.49-2.26) after a mean follow-up of 2.3 years.ConclusionRevascularization was associated with a lower risk of all-cause mortality in NSTEMI patients with severe CKD. For non–dialysis-dependent patients who survived to discharge, revascularization was associated with a higher risk of progression to chronic hemodialysis.     

Poor outcomes associated with antithrombotic undertreatment in patients with atrial fibrillation attending Gondar University Hospital: a retrospective cohort study

Background

Atrial fibrillation (AF) is a major risk factor for stroke as it increases the incidence of stroke nearly fivefold. Antithrombotic treatment is recommended for the prevention of stroke in AF patients. However, majorly due to fear of risk of bleeding, adherence to recommendations is not observed. The aim of this study was to investigate the impact of antithrombotic undertreatment, on ischemic stroke and/or all-cause mortality in patients with AF.

Methods

A retrospective cohort study was conducted from January 7, 2017 to April 30 2017 using medical records of patients with AF attending Gondar University Hospital (GUH) between November 2012 and September 2016. Patients receiving appropriate antithrombotic management and those on undertreatment, were followed for development of ischemic stroke and/or all-cause mortality. Kaplan-Meier and a log-rank test was used to plot the survival analysis curve. Cox regression was used to determine the predictors of guideline-adherent antithrombotic therapy.

Results

The final analysis included 159 AF patients with a median age of 60 years. Of these, nearly two third (64.78%) of patients were receiving undertreatment for antithrombotic medications. Upon multivariate analysis, history of ischemic stroke/transient ischemic attack (TIA) was associated with lower incidence of antithrombotic undertreatment. A significant increase (HR: 8.194, 95% CI: 2.911–23.066)] in the incidence of ischemic stroke and/or all-cause mortality was observed in patients with undertreatment. Up-on multivariate analysis, only increased age was associated with a statistically significant increase incidence of ischemic stroke and/or all-cause mortality, while only history of ischemic stroke/TIA was associated with a decrease in the risk of ischemic stroke and/or all-cause mortality.

Conclusion

Adherence to antithrombotic guideline recommendations was found to be crucial in reducing the incidence of ischemic stroke and/or all-cause mortality in patients with AF without increasing the risk of bleeding. However, undertreatment to antithrombotic medications was found to be high (64.78%) and was associated with poorer outcomes in terms of ischemic stroke and/or all-cause mortality. Impact on practice: This research highlighted the magnitude of antithrombotic undertreatment and its impact on ischemic stroke and/or all-cause mortality in patients with AF. This article has to alert prescribers to routinely evaluate AF patients’ risk for ischemic stroke and provide appropriate interventions based on guideline recommendations.

     

Superiority of high sensitivity cardiac troponin T vs. I for long-term prognostic value in patients with chest pain; data from the Akershus cardiac Examination (ACE) 3 study

BackgroundCardiac troponins (cTn) are essential in the diagnostic assessment of non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Elevated concentrations of cTnT and cTnI predict cardiovascular events in non-acute settings, but the individual troponin isotype association with long-term mortality in patients with suspected unstable angina pectoris (UAP) is less clear.MethodsPatients hospitalized with chest pain between June 2009 and December 2010 were included in the Akershus Cardiac Examination 3 Study and followed for median 6.6 (IQR 6.2-7.1) years. The index diagnosis was adjudicated by an independent committee as NSTE-myocardial infarction (NSTEMI), UAP or non-ACS. Blood samples were collected within 24 h of admission and analyzed with high sensitivity assays for cTnT (hs-cTnT, Roche) and cTnI (hs-cTnI, Singulex).ResultsOf 402 patients included, 74 (18%) were classified as NSTEMI, 88 (22%) UAP and 240 (60%) non-ACS. hs-cTnI concentrations were detectable in all patients (median 3 [IQR 1–11] ng/L), while hs-cTnT concentrations were above the level of blank in 205 (51%) (median 3 [IQR 3–16] ng/L). In patients with UAP, both log₂-transformed hs-cTnT and hs-cTnI were associated with all-cause mortality in analyses that adjusted for other risk factors: HR 2.40 [95% CI 1.75–3.30], p < 0.001 and HR 1.44 [1.14–1.81], p = 0.002. There were no significant sex-dependent differences in the association between hs-cTnT or hs-cTnI and outcome. Time dependent receiver-operating characteristics area under the curve was 0.85 (95% CI 0.79–0.92) for hs-cTnT and 0.74 (0.64–0.84) for hs-cTnI, p = 0.008 for difference between values.ConclusionsHigher concentrations of hs-cTnT and hs-cTnI were both associated with all-cause mortality in patients with UAP, but the association with outcome was stronger for hs-cTnT than for hs-cTnI.     

The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock

BackgroundEarly antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes.MethodsED-treated adults (≥18 years; n = 1075) with severe sepsis or septic shock receiving ≥2 doses of intravenous antibiotics were assessed, retrospectively, for second-dose antibiotic delays (dose time > 25% of recommended interval). Predictors of delay and impact on outcomes were determined, controlling for MEDS score, 30 mL/kg fluids and antibiotics within three hours of sepsis onset, lactate, and renal failure, among others.ResultsIn total, 335 (31.2%) patients had delayed second-dose antibiotics. A total of 1864 second-dose antibiotics were included, with 354 (19.0%) delays identified by interval (delayed/total doses): 6-h (36/67) = 53.7%; 8-h (165/544) = 30.3%; 12-h (114/436) = 26.1%; 24-h (21/190) = 8.2%; 48-h (0/16) = 0%. In-hospital mortality in the timely group was 15.5% (shock-17.6%) and 13.7% in the delayed group (shock-16.9%). Increased odds of delay were observed for ED boarding (OR 2.54, 95% 1.81–3.55), shorter dosing intervals (6/8-h- OR 2.99, 95% CI 1.95–4.57; 12-h- OR 2.46, 95% CI 1.72–3.51), receiving 30 mL/kg fluids by three hours (OR 1.42, 95% CI 1.06–1.90), and renal failure (OR 2.57, 95% CI 1.50–4.39). Delays were not associated with increased mortality (OR 0.87, 95% CI 0.58–1.29) or other outcomes.ConclusionsFactors associated with delayed second-dose antibiotics include ED boarding, antibiotics requiring more frequent dosing, receiving 30 mL/kg fluid, and renal failure. Delays in second-dose administration were not associated with mortality or other outcomes.     

Lower Extremity Arterial Disease as a Predictor of Incident Atrial Fibrillation and Cardiovascular Events

ObjectiveTo evaluate the relationship between peripheral arterial disease (PAD) and incident atrial fibrillation (AF) and its clinical and pathophysiologic implications on ischemic stroke and all-cause mortality.Patients and MethodsWe identified all adult patients in the Mayo Clinic Health System without a previous diagnosis of AF undergoing ankle-brachial index (ABI) testing for any indication from January 1, 1996, to June 30, 2018. Retrospective extraction of ABI data and baseline echocardiographic data was performed. The primary outcome of interest was incident AF. The secondary outcomes of interest were incident ischemic stroke and all-cause mortality.ResultsA total of 33,734 patients were included in the study. After adjusting for demographic and comorbidity variables, compared with patients who had normal ABI (1.0 to 1.39), there was an increased risk of incident AF in patients with low ABI (<1.0) (adjusted hazard ratio, 1.14; 95% CI, 1.06 to 1.22) and elevated ABI (≥1.4) (adjusted hazard ratio, 1.18; 95% CI, 1.06 to 1.31). The risk was greater in patients with increasing severity of PAD. Patients with abnormal ABIs had an increased risk of ischemic stroke and all-cause mortality. We found that patients with PAD and incident AF have certain baseline echocardiographic abnormalities.ConclusionIn this large cohort of ambulatory patients undergoing ABI measurement, patients with PAD were at increased risk for incident AF, ischemic stroke, and mortality. In these high-risk patients with abnormal ABI, particularly severe PAD and cardiac structural abnormalities, routine monitoring for AF and management of cardiovascular risk factors may be warranted.