Effectiveness and Safety of Clopidogrel vs Aspirin in Elderly Patients With Ischemic Stroke

ObjectiveTo evaluate the risks of recurrent stroke and major bleeding events with clopidogrel and aspirin use among patients aged 80 years or older.Patients and MethodsThis retrospective cohort study was conducted using the Full Population Data of the Health and Welfare Database in Taiwan. Patients aged 80 years or older who received monotherapy with clopidogrel or aspirin following hospitalization for primary acute ischemic stroke between January 1, 2009, and December 31, 2018, were included. Inverse probability of treatment weighting was used to balance measured covariates between clopidogrel and aspirin users. Measured outcomes included recurrent acute ischemic stroke, acute myocardial infarction, composite cardiovascular events (recurrent stroke or acute myocardial infarction), intracranial hemorrhage, major gastrointestinal tract bleeding, and composite major bleeding events (intracranial hemorrhage or major gastrointestinal tract bleeding).ResultsA total of 15,045 patients were included in the study, 1979 of whom used clopidogrel and 13,066 who used aspirin following hospitalization for primary acute ischemic stroke. Clopidogrel use was associated with significantly lower risk of recurrent acute ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.83 to 0.96; P=.002), composite cardiovascular events (HR, 0.88; 95% CI, 0.82 to 0.95; P<.001), intracranial hemorrhage (HR, 0.71; 95% CI, 0.56 to 0.90; P=.005), and composite major bleeding events (HR, 0.89; 95% CI, 0.80 to 0.99; P=.04) compared with aspirin use.ConclusionIn patients aged 80 years or older with primary acute ischemic stroke, clopidogrel users had lower risks of recurrent stroke and the composite cardiovascular events compared with aspirin users. Clopidogrel users also had lower risks of intracranial hemorrhage and the composite major bleeding events compared with aspirin users.     

The Association of Sleep Apnea and Cardiorespiratory Fitness With Long-Term Major Cardiovascular Events

ObjectiveTo determine the risk of long-term major adverse cardiovascular events (MACE) when sleep-disordered breathing (SDB) and decreased cardiorespiratory fitness (CRF) co-occur.MethodsWe included consecutive patients who underwent symptom-limited cardiopulmonary exercise tests between January 1, 2005, and January 1, 2010, followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-to-severe SDB (apnea/hypopnea index ≥15 per hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO₂). Long-term MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke or transient ischemic attack (TIA), and death, assessed until May 21, 2018. Cox-proportional hazard models were adjusted for factors known to influence CRF and MACE.ResultsOf 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5 to 10.3 years). After adjusting for age, sex, beta blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking, and use of positive airway pressure (PAP), decreased CRF alone (hazard ratio [HR]=1.91, 95% confidence interval [CI], 1.15 to 3.18; P=.01), but not SDB alone (HR=1.26, 95% CI, 0.75 to 2.13, P=.39) was associated with increased risk of MACE. Those with SDB and decreased CRF had greater risk of MACE compared with patients with decreased CRF alone (HR=1.85; 95% CI, 1.21 to 2.84; P<.005) after accounting for these confounders. The risk of MACE was attenuated in those with reduced CRF alone after additionally adjusting for adequate adherence to PAP (HR=1.59; 95% CI, 0.77 to 3.31; P=.21).ConclusionThe incidence of MACE, especially mortality, was high in this sample. Moderate-to-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of possibly including CRF in the risk assessment of patients with SDB and, conversely, that of screening for SDB in patients with low peak VO₂.     

Clinical Characteristics,Management Strategies and Outcomes of Acute Myocardial Infarction Patients With Prior Coronary Artery Bypass Grafting

ObjectiveTo investigate the management strategies, temporal trends, and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery and presenting with acute myocardial infarction (MI).Patients and MethodsWe undertook a retrospective cohort study using the National Inpatient Sample database from the United States (January 2004–September 2015), identified all inpatient MI admissions (7,250,768 records) and stratified according to history of CABG (group 1, CABG-naive [94%]; group 2, prior CABG [6%]).ResultsPatients in group 2 were older, less likely to be female, had more comorbidities, and were more likely to present with non-ST-elevation myocardial infarction compared with group 1. More patients underwent coronary angiography (68% vs 48%) and percutaneous coronary intervention (PCI) (44% vs 26%) in group 1 compared with group 2. Following multivariable logistic regression analyses, the adjusted odd ratio (OR) of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.98; 95% CI, 0.95 to 1.005; P=.11), all-cause mortality (OR, 1; 95% CI, 0.98 to 1.04; P=.6) and major bleeding (OR, 0.99; 95% CI, 0.94 to 1.03; P=.54) were similar to group 1. Lower adjusted odds of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.64; 95% CI, 0.57 to 0.72; P<.001), all-cause mortality (OR, 0.45; 95% CI, 0.38 to 0.53; P<.001), and acute ischemic stroke (OR, 0.71; 95% CI, 0.59 to 0.86; P<.001) were observed in group 2 patients who underwent PCI compared with those managed medically without any increased risk of major bleeding (OR, 1.08; 95% CI, 0.94 to 1.23; P=.26).ConclusionsIn this national cohort, MI patients with prior-CABG had a higher risk profile, but similar in-hospital adverse outcomes compared with CABG-naive patients. Prior-CABG patients who received PCI had better in-hospital clinical outcomes compared to those who received medical management.     

Age-Related 2-Year Mortality After Transcatheter Aortic Valve Replacement: the YOUNG TAVR Registry

ObjectiveTo comparatively assess the natural history of patients of different ages undergoing transcatheter aortic valve replacement (TAVR).Patients and MethodsFor this study, we used the YOUNG TAVR, an international, multicenter registry investigating mortality trends up to 2 years in patients with aortic valve stenosis treated by TAVR, classified according to 3 prespecified age groups: 75 years or younger (n=179), 76 to 86 years (n=602), and older than 86 years (n=221). A total of 1002 patients undergoing TAVR were included. Demographic, clinical, and outcome data in the youngest group were compared with those of patients 76 to 86 years and older than 86 years. Patients were followed up for up to 2 years.ResultsCompared with patients 75 years or younger (reference group), patients aged 76 to 86 years and older than 86 years had nonsignificantly different 30-day mortality (odds ratio, 0.76; 95% CI, 0.41-1.38; P=.37 and odds ratio, 1.27; 95% CI, 0.62-2.60; P=.51, respectively) and 1-year mortality (hazard ratio (HR), 0.72; 95% CI, 0.48-1.09; P=.12 and HR, 1.11; 95% CI, 0.88-1.40; P=.34, respectively). Mortality at 2 years was significantly lower among patients aged 76 to 86 years (HR, 0.62; 95% CI, 0.42-0.90; P=.01) but not among the older group (HR, 1.06; 95% CI, 0.68-1.67; P=.79). The Society of Thoracic Surgeons 30-day mortality score was lower in younger patients who, however, had a significantly higher prevalence of chronic obstructive pulmonary disease (P=.005 vs the intermediate group and P=.02 vs the older group) and bicuspid aortic valves (P=.02 vs both older groups), larger left ventricles, and lower ejection fractions.ConclusionIn the present registry, mortality at 2 years after TAVR among patients 75 years or younger was higher compared with that of patients aged 75 to 86 years and was not markedly different from that of patients older than 86 years. The findings are attributable at least in part to a greater burden of comorbidities in the younger age group that are not entirely captured by current risk assessment tools.     

Long-Term Risk of Major Adverse Cardiac Events in Atrial Fibrillation Patients on Direct Oral Anticoagulants

ObjectiveTo determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF).Patients and MethodsThis study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death.ResultsThe mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (<75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses.ConclusionDOACs are associated with a lower risk of MACE in patients with AF independently from dosage.     

Arterial Thrombotic Events in Adult Inpatients With COVID-19

ObjectiveTo evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19).MethodsAll consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form.ResultsOverall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001).ConclusionA dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.     

Survival and Progression in Synucleinopathy Phenotypes With Parkinsonism: A Population-Based Study

ObjectiveTo compare survival by the presenting parkinsonism symptoms at diagnosis among patients with incident clinically diagnosed synucleinopathies.Patients and MethodsUsing the Rochester Epidemiology Project medical records–linkage system, we identified all persons residing in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from January 1, 1991, through December 31, 2010. A movement disorder specialist reviewed the complete medical records of each individual to confirm the presence of parkinsonism, determine the type of synucleinopathy, and identify the onset dates of each cardinal symptom (tremor at rest, bradykinesia, rigidity, and impaired postural reflexes). We determined the median time from age at diagnosis to death or censoring (June 30, 2015) for each presenting symptom and the age- and sex-adjusted risk of death.ResultsFrom 1991 through 2010, a total of 433 individuals had a synucleinopathy diagnosed (301 [69.5%], Parkinson disease; 68 [15.7%], dementia with Lewy bodies; 52 [12.0%], Parkinson disease dementia; and 12 [2.8%], multiple systems atrophy with parkinsonism). Overall, the risk of death in the tremor-predominant group was less than that in the bradykinesia/rigidity-only group (hazard ratio [HR], 0.59; 95% CI, 0.40-0.87; P=.007). Similarly, risk of death in the bradykinesia/rigidity-only group was significantly greater than in the tremor-predominant group (HR, 1.75; 95% CI, 1.23-2.51; P=.002) and compared with tremor before bradykinesia (HR, 1.75; 95% CI, 1.24-2.47; P=.001).ConclusionPatients with tremor as a presenting symptom have longer survival. In contrast, the presence of bradykinesia/rigidity as a presenting symptom correlates with reduced survival across all types of synucleinopathies.     

Repeat Coronary Bypass Surgery or Percutaneous Coronary Intervention After Previous Surgical Revascularization

ObjectiveTo assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG.MethodsFrom January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used.ResultsIn multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P<.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65).ConclusionRCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.     

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation,Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD.Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles).ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001].ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.     

Long-term Cardiovascular Risk in Astronauts: Comparing NASA Mission Astronauts With a Healthy Cohort From the Cooper Center Longitudinal Study

ObjectiveTo determine the long-term cardiovascular disease risk of astronauts with spaceflight exposure compared with a well-matched cohort.MethodsNational Aeronautics and Space Administration (NASA) astronauts are selected into their profession based upon education, unique skills, and health and are exposed to cardiovascular disease risk factors during spaceflight. The Cooper Center Longitudinal Study (CCLS) is a generally healthy cohort from a preventive medicine clinic in Dallas, Texas. Using a matched cohort design, astronauts who were selected beginning April 1, 1959, (and each subsequent selection class through 2009) and exposed to spaceflight were matched to CCLS participants who met astronaut selection criteria; 1514 CCLS participants matched to 303 astronauts in a 5-to-1 ratio on sex, date of birth, and age. The outcome of cardiovascular mortality through December 31, 2016, was determined by death certificate or National Death Index.ResultsThere were 11 deaths caused by cardiovascular disease (CVD) among astronauts and 46 among CCLS participants. There was no evidence of increased mortality risk in astronauts (hazard ratio [HR]=1.10; 95% confidence interval [CI], 0.50 to 2.45) with adjustment for baseline cardiovascular covariates. However, the secondary outcome of CVD events showed an increased adjusted risk in astronauts (HR=2.41; 95% CI, 1.26 to 4.63).ConclusionNo increased risk of CVD mortality was observed in astronauts with spaceflight exposure compared with a well-matched cohort, but there was evidence of increased total CVD events. Given that the duration of spaceflight will increase, particularly on missions to Mars, continued surveillance and mitigation of CVD risk is needed to ensure the safety of those who venture into space.     

Noninvasive Voice Biomarker Is Associated With Incident Coronary Artery Disease Events at Follow-up

ObjectiveTo evaluate the association between a preidentified voice biomarker and incident coronary artery disease (CAD) events.MethodsPatients referred for clinically indicated coronary angiography underwent a total of three 30-second voice recordings using the Vocalis Health smartphone application between January 1, 2015, and February 28, 2017. A pre-established voice biomarker was derived from each individual recording, and the mean biomarker value was calculated for each patient. Individuals were clinically observed through December 31, 2019. The prespecified primary outcome was a composite of presenting to the emergency department with chest pain, being admitted to the hospital with chest pain, or having an acute coronary syndrome; the prespecified secondary outcome was a composite of a positive stress test result at follow-up or the presence of CAD at follow-up coronary angiography.ResultsIn the final analysis, 108 patients were included (mean age, 59.47±11.44 years; male, 59 [54.6%]). The median follow-up time was 24 months (range, 1 to 60 months). In multivariable Cox proportional hazards models adjusting for CAD grade on baseline angiography, a high baseline mean voice biomarker was significantly associated with both the primary (hazard ratio, 2.61; 95% CI, 1.42 to 4.80; P=.002) and secondary (hazard ratio, 3.13; 95% CI, 1.13 to 8.68; P=.03) composite outcomes.ConclusionThis study found a significant association between a noninvasive voice biomarker and incident CAD events at follow-up. These results may have important clinical implications for the remote and noninvasive screening of patients to identify those at risk of coronary disease and its complications.     

Efficacy and Safety of Lower Limb Progressive Resistance Exercise for Patients With Total Knee Arthroplasty: A Meta-analysis of Randomized Controlled Trials

ObjectiveTo evaluate the efficacy and safety of progressive resistance exercise (PRE) for patients with total knee arthroplasty (TKA) in a meta-analysis.Data SourcesPubMed, MEDLINE, Cochrane’s Library, and EMBASE databases.Study SelectionRandomized controlled trials evaluating the effect of PRE on mobility and function in patients with TKA.Data ExtractionA random-effects model was applied if significant heterogeneity was detected; otherwise, a fixed-effects model was applied.Data SynthesisSeven randomized controlled trials. Compared with a rehabilitation program without PRE, physiotherapy including PRE was associated with improvements in the 6-minute walking test (weighed mean difference [WMD], 19.22m; P=.04) with a wide confidence interval (CI, 0.48～37.95). However, sensitivity analysis by omitting 1 study with preoperative rehabilitation revealed nonsignificant results (WMD, 15.15m; P=.16). Moreover, PRE did not significantly improve the maximal walking speed (WMD, 0.05m/s, 95% CI, 0.00～0.11; P=.05). However, PRE was associated with improved knee strength of extension (standardized mean difference [SMD], 0.72; 95% CI, 0.47～0.96; P<.001) and flexion (SMD, 0.47; 95% CI, 0.19～0.74; P<.001) but not self-reported physical function (SMD, ?0.17; 95% CI, ?0.37～0.03; P=.10) or changes in pain score (SMD, 0.11; 95% CI, ?0.15～0.37; P=.40). PRE did not increase the risk of adverse events (risk ratio, 1.19; 95% CI, 0.52～2.71; P=.68).ConclusionsPRE may lead to improvements in physical function among patients receiving a TKA. PRE leads to higher ultimate strength in the surgical knee and is safe to perform.     

Prognostic Interplay Between Coronary Artery Calcium Scoring and Cardiorespiratory FItness: The CAC-FIT Study

ObjectiveTo assess the incremental prognostic role of coronary artery calcium score (CACS) and exercise capacity (EC), two independent prognostic tests in the assessment of patients with coronary artery disease.MethodsThe cohort consisted of patients who had clinically indicated exercise stress testing and CACS assessment from January 1, 2015, to September 30, 2021, with a median of 27 days between each other. Exercise capacity was defined by peak metabolic equivalents of task (METs) achieved during exercise stress test. The CACS was determined by the Agatston method. Patients were observed from the latest test date to incident major adverse cardiac events (inclusive of all-cause death, nonfatal myocardial infarction, late revascularization, and admission for heart failure).ResultsThere were a` total of 1932 patients in the study population (mean age, 56±12 years; 42% female, 48% hypertension, 21% diabetes, 48% dyslipidemia). Peak METs below 6 was achieved in 8% of patients, and the median (interquartile range) CACS was 9 (0-203). In multivariable Cox regression models, both CACS (1 unit increase in log CACS: hazard ratio, 1.19; 95% CI, 1.06 to 1.34; P=.003;) and EC (1 unit increase in peak METs: hazard ratio, 0.89; 95% CI, 0.81 to 0.97; P=.01) were independently associated with outcomes. Using CACS+EC added incremental prognostic value over clinical and fitness models (C index increase from 0.68 to 0.75; P=.015). Incident event rates increased across categories of CACS and EC.ConclusionOur analysis found that CACS and EC have complementary risk-stratifying roles in coronary artery disease.     

Continuous Renal Replacement Therapy Liberation and Outcomes of Critically Ill Patients With Acute Kidney Injury

ObjectiveTo examine the association between continuous renal replacement therapy (CRRT) liberation and clinical outcomes among patients with acute kidney injury (AKI) requiring CRRT.MethodsThis single-center, retrospective cohort study included adult patients admitted to intensive care units with AKI and treated with CRRT from January 1, 2007, to May 4, 2018. Based on the survival and renal replacement therapy (RRT) status at 72 hours after the first CRRT liberation, we classified patients into liberated, reinstituted, and those who died. We observed patients for 90 days after CRRT initiation to compare the major adverse kidney events (MAKE₉₀).ResultsOf 1135 patients with AKI, 228 (20%), 437 (39%), and 470 (41%) were assigned to liberated, reinstituted, and nonsurvival groups, respectively. The MAKE₉₀, mortality, and RRT independence rates of the cohort were 62% (707 cases), 59% (674 cases), and 40% (453 cases), respectively. Compared with reinstituted patients, the liberated group had a lower MAKE₉₀ (29% vs 39%; P=.009) and higher RRT independence rate (73% vs 65%; P=.04) on day 90, but without significant difference in 90-day mortality (26% vs 33%; P=.05). After adjustments for confounders, successful CRRT liberation was not associated with lower MAKE₉₀ (odds ratio, 0.71; 95% CI, 0.48 to 1.04; P=.08) but was independently associated with improved kidney recovery at 90-day follow-up (hazard ratio, 1.81; 95% CI, 1.41 to 2.32; P<.001).ConclusionOur study demonstrated a high occurrence of CRRT liberation failure and poor 90-day outcomes in a cohort of AKI patients treated with CRRT.     

Cardioselective Versus Nonselective β-Blockers After Myocardial Infarction in Adults With Chronic Obstructive Pulmonary Disease

ObjectiveTo investigate which types of β-blockers have better efficacy and safety profiles in patients with concomitant chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI) to address concerns about use of β-blockers in COPD.MethodsWe identified 65,699 patients with COPD prescribed β-blockers after first MI in the Taiwan National Health Insurance Research Database between January 1, 2001, and December 31, 2013. Comparisons were performed using the inverse probability of treatment weighting method. The primary outcome was all-cause mortality; secondary outcomes were heart failure hospitalization, major adverse cardiac and cerebrovascular event (MACCE), and major adverse pulmonary event (MAPE).ResultsA total of 14,789 patients prescribed β-blockers were enrolled, of whom 7247 (49.0%) used cardioselective β-blockers and 7542 (51.0%) used nonselective β-blockers. The cardioselective group had lower incidence rates of mortality (hazard ratio [HR], 0.93; 95% CI, 0.89 to 0.96), MACCE (HR, 0.96; 95% CI, 0.93 to 0.998), heart failure hospitalization (subdistribution HR, 0.84; 95% CI, 0.78 to 0.91), and MAPE (HR, 0.94; 95% CI, 0.90 to 0.98) at the end of follow-up after weighting. Similar results were also found in subgroup analysis between those prescribed bisoprolol and those prescribed carvedilol.ConclusionPatients prescribed a cardioselective β-blocker may have a lower incidence of all-cause mortality, MACCE, heart failure hospitalization, and MAPE than those prescribed a nonselective β-blocker. Cardioselective β-blocker treatment during hospitalization and continuing after discharge appears to be superior to nonselective β-blocker treatment in patients with COPD after MI.     

Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials

ObjectivesTo quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention and the effect of dosage.MethodsThis study is designed as a random effects meta-analysis and meta-regression of randomized control trials with EPA/DHA supplementation. This is an update and expanded analysis of a previously published meta-analysis which covers all randomized control trials with EPA/DHA interventions and cardiovascular outcomes published before August 2019. The outcomes included are myocardial infarction (MI), coronary heart disease (CHD) events, CVD events (a composite of MI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduled cardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.ResultsA total of 40 studies with a combined 135,267 participants were included. Supplementation was associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certainty number needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certainty NNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT = 128; and CHD mortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT = 431, but not CVD events (RR, 0.95; 95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI.ConclusionCardiovascular disease remains the leading cause of death worldwide. Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.     

Macrovascular Thrombotic Events in a Mayo Clinic Enterprise-Wide Sample of Hospitalized COVID-19–Positive Compared With COVID-19–Negative Patients

ObjectiveTo determine the difference in the rate of thromboembolic complications between hospitalized coronavirus disease 2019 (COVID-19)–positive compared with COVID-19–negative patients.Patients and MethodsAdult patients hospitalized from January 1, 2020, through May 8, 2020, who had COVID-19 testing by polymerase chain reaction assay were identified through electronic health records across multiple hospitals in the Mayo Clinic enterprise. Thrombotic outcomes (venous and arterial) were identified from the hospital problem list.ResultsWe identified 3790 hospitalized patients with COVID-19 testing across 19 hospitals, 102 of whom had positive test results. The median age was lower in the COVID-positive patients (62 vs 67 years; P=.03). The median duration of hospitalization was longer in COVID-positive patients (8.5 vs 4 days; P<.001) and more required intensive care unit care (56.9% [58 of 102] vs 26.8% [987 of 3688]; P<.001). Comorbidities, including atrial fibrillation/flutter, heart failure, chronic kidney disease, and malignancy, were observed less frequently with COVID-positive admissions. Any venous thromboembolism was identified in 2.9% of COVID-positive patients (3 of 102) and 4.6% of COVID-negative patients (168 of 3688). The frequency of venous and arterial events was not different between the groups. The unadjusted odds ratio (OR) for COVID-positive–patients for any venous thromboembolism was 0.63 (95% CI, 0.19 to 2.02). A multivariable logistic regression model evaluated death within 30 days of hospital discharge; neither COVID positivity (adjusted OR, 1.12; 95% CI, 0.54 to 2.34) nor thromboembolism (adjusted OR, 0.90; 95% CI, 0.60 to 1.32) was associated with death.ConclusionEarly experience in patients with COVID-19 across multiple academic and regional hospitals representing different US regions demonstrates a lower than previously reported incidence of thrombotic events. This incidence was not higher than a contemporary COVID-negative hospitalized comparator.     

Drug Treatment,Postural Control,and Falls: An Observational Cohort Study of 504 Patients With Acute Stroke,the Fall Study of Gothenburg

ObjectiveTo identify whether, and to what extent, treatment with cardiovascular drugs and neurotropic drugs are associated with postural control and falls in patients with acute stroke.DesignObservational cohort study.SettingA stroke unit at a university hospital.ParticipantsA consecutive sample of patients (N=504) with acute stroke.InterventionsNot applicable.Main Outcome MeasuresPostural control was assessed using the modified version of the Postural Assessment Scale for Stroke Patients. Data including baseline characteristics, all drug treatments, and falls were derived from medical records. Univariable and multivariable logistic regression and Cox proportional hazards models were used to analyze the association of drug treatment and baseline characteristics with postural control and with falls.ResultsIn the multivariable logistic regression analysis, factors significantly associated with impaired postural control were treatment with neurotropic drugs (eg, opioids, sedatives, hypnotics, antidepressants) with an odds ratio (OR) of 1.73 (95% confidence interval [CI], 1.01-2.97, P=.046); treatment with opioids (OR 9.23, 95% CI, 1.58-54.00, P=0.014); age (OR 1.09, 95% CI, 1.07-1.12, P<.0001), stroke severity, which had a high National Institutes of Health Stroke Scale-score (OR 1.29, 95% CI, 1.15-1.45, P<.0001), and sedentary life style (OR 4.32, 95% CI, 1.32-14.17, P=.016). No association was found between neurotropic drugs or cardiovascular drugs and falls.ConclusionsTreatment with neurotropic drugs, particularly opioids, in the acute phase after stroke, is associated with impaired postural control. Since impaired postural control is the major cause of falls in patients with acute stroke, these results suggest opioids should be used with caution in these patients.     

The Role of Biological Effective Dose in Predicting Obliteration After Stereotactic Radiosurgery of Cerebral Arteriovenous Malformations

ObjectiveTo determine whether biological effective dose (BED) was predictive of obliteration after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs).Patients and MethodsWe studied patients undergoing single-session AVM SRS between January 1, 1990, and December 31, 2014, with at least 2 years of imaging follow-up. Excluded were patients with syndromic AVM, previous SRS or embolization, and patients treated with volume-staged SRS. Biological effective dose was calculated using a mono-exponential model described by Jones and Hopewell. The primary outcome was likelihood of total obliteration defined by digital subtraction angiography or magnetic resonance imaging (MRI). Variables were analyzed as continuous and dichotomous variables based on the maximum value of (sensitivity–[1–specificity]).ResultsThis study included 352 patients (360 AVM, median follow-up, 5.9 years). The median margin dose prescribed was 18.75 Gy (interquartile range [IQR]: 18 to 20 Gy). Two hundred fifty-nine patients (71.9%) had obliteration shown by angiography (n=176) or MRI (n=83) at a median of 36 months after SRS (IQR: 26 to 44 months). Higher BED was associated with increased likelihood of obliteration in univariate Cox regression analyses, when treated as either a dichotomous (≥133 Gy; hazard ratio [HR],1.52; 95% confidence interval [CI], 1.19 to 1.95; P<.001) or continuous variable (HR, 1.00, 95% CI, 1.0002 to 1.005; P=.04). In multivariable analyses including dichotomized BED and location, BED remained associated with obliteration (P=.001).ConclusionBiological effective dose ≥133 Gy was predictive of AVM obliteration after single-session SRS within the prescribed margin dose range 15 to 25 Gy. Further study is warranted to determine whether BED optimization should be considered as well as treatment dose for AVM SRS planning.