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The Anticoagulation Length of Therapy and Risk of New Adverse Events In Venous Thromboembolism (ALTERNATIVE) study was designed to compare the benefits and harms of different treatment options for extended treatment of venous thromboembolism (VTE). In this paper, we describe the study cohort, survey data collection, and preliminary results. We identified 39,605 adult patients (age ≥ 18 years) from two large integrated health care delivery systems who were diagnosed with incident VTE and received initial anticoagulation therapy of 3 months or longer. A subset of the cohort (12,737) was invited to participate in a survey. Surveys were completed in English, Spanish or Mandarin via a mailed questionnaire, an online secure web link, or telephone. The survey domains included demographics, personal medical history, anticoagulant treatment history, anticoagulant treatment satisfaction, health-related quality of life and health literacy. A total of 5,017 patients participated in the survey for an overall response rate of 39.4%. The mean (SD) age of the survey respondents was 63.0 (14.5) years and self-reported race was 76.0% White/European, 11.1% Black/African American, and 3.8% Asian/Pacific Islander and 14.0% reported Hispanic ethnicity. Sixty percent of respondents completed the web survey, while 29.0% completed the mail-in paper survey, and 11.0% completed the survey via telephone. The ALTERNATIVE Study will address knowledge gaps by comparing several treatment alternatives for the extended management of VTE so that this information could be used by patients and clinicians to make more informed, patient-centered treatment choices. [ABSTRACT FROM AUTHOR]

Background: The impact of the novel coronavirus disease 2019 (COVID‐19) pandemic on diet and nutrition among older adults with chronic medical conditions have not been well‐described. Methods: We conducted a survey addressing (1) food access, (2) diet quality and composition, (3) nutritional understanding, and (4) attitudes towards research among adults with heart failure (HF) within an integrated health system. Adults (≥18 years) with diagnosed HF and at least one prior hospitalization for HF within the last 12 months were approached to complete the survey electronically or by mail. Outcomes included all‐cause and HF‐specific hospitalizations and all‐cause death was ascertained via the electronic health record. Results: Among 1212 survey respondents (32.5% of eligible patients) between May 18, 2020 and September 30, 2020, mean ± SD age was 77.9 ± 11.4 years, 50.1% were women, and median (25th–75th) left ventricular ejection fraction was 55% (40%–60%). Overall, 15.1% of respondents were food insecure, and only 65% of participants answered correctly more than half of the items assessing nutritional knowledge. Although most respondents were willing to participate in future research, that number largely declined for studies requiring blood draws (32.2%), study medication (14.4%), and/or behavior change (27.1%). Food security, diet quality, and nutritional knowledge were not independently associated with outcomes at 90 or 180 days. Conclusion: In a cohort of older adults with HF and multiple comorbidities, a significant proportion reported issues with food access, diet quality, and nutritional knowledge during the COVID‐19 pandemic. Future research should evaluate interventions targeting these domains in at‐risk individuals. Key points: Upwards of 15% of respondents screened positive for food insecurity, and only approximately 65% of respondents answered more than half of the items correctly on a questionnaire assessing nutritional understanding.Although the majority of respondents indicated that would be willing to consider participating in future research, that proportion declined markedly for studies requiring blood draws, study drugs, and/or behavior change.None of the functional domains assessed by this survey were independently associated with clinical outcomes in our cohort. [ABSTRACT FROM AUTHOR]

Purpose: Our objective was to calculate the positive predictive value (PPV) of the ICD‐9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter‐rater reliability of physician adjudication. Methods: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin‐converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician‐adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD‐9‐CM code 995.1) meeting the inclusion criteria. The inter‐rater reliability of physician teams, or kappa statistic, was also calculated. Results: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient‐years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter‐rater reliability was 0.65 (95% CI: 0.47, 0.82). Conclusions: ICD‐9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI. [ABSTRACT FROM AUTHOR]

Background: Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking.Research Question: Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19?Study Design and Methods: We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between February 2020 and August 2020 from two integrated health-care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19.Results: We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/μL.Interpretation: Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19. [ABSTRACT FROM AUTHOR]

Background: To examine the individual and combined associations of noncardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF).Methods: We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of noncardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause.Results: Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 noncardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 noncardiac conditions/mobility limitation, ≥3 noncardiac conditions/no mobility limitation, ≥3 noncardiac conditions/mobility limitation (vs) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of noncardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age.Conclusions: There is an additive association of mobility limitation, beyond the burden of noncardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies. DESIGN: Retrospective cohort study. SETTING: Seven US healthcare delivery systems. PARTICIPANTS: Adults with left ventricular systolic dysfunction receiving an implantable cardioverter‐defibrillator (ICD) for primary prevention. MEASUREMENTS: Data on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0‐3, 4‐5, 6‐7 and 8‐16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy. RESULTS: Among 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4‐8), with 98% having at least two comorbidities. During a mean 2.2 years of follow‐up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14‐3.31] for 4‐5 comorbidities; HR = 2.25 [95% CI = 1.25‐4.05] for 6‐7 comorbidities; and HR = 2.91 [95% CI = 1.54‐5.50] for 8‐16 comorbidities). Participants with 8‐16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43‐3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67‐6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07‐2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies. CONCLUSIONS: In primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation. [ABSTRACT FROM AUTHOR]

OBJECTIVES To assess multimorbidity burden and its association with clinical outcomes in adults with heart failure (HF) according to sex, age, and HF type. DESIGN Retrospective cohort study. SETTING Five healthcare delivery systems across the United States. PARTICIPANTS Adults with HF (N=114,553). MEASUREMENTS We characterized participants with respect to the presence of 26 chronic conditions categorized into quartiles based on overall burden of comorbidity (<5, 5–6, 7–8, ≥9). Outcomes included all‐cause death and hospitalization for HF or any cause. Multivariable Cox regression was used to evaluate the adjusted association between categorized burden of multimorbidity burden and outcomes. RESULTS: Individuals with more morbidities were more likely to die than those with fewer then 5 morbidities (5–6 morbidities: adjusted hazard ratio (aHR)=1.27 (95% confidence interval (CI)=1.24–1.31; 7–8 morbidities: aHR=1.52, 95% CI=1.48–1.57; ≥9 morbidities: aHR=1.92, 95% CI=1.86–1.99). There was a graded, higher adjusted rate of any‐cause hospitalization associated with 5 or 6 (aHR=1.28, 95% CI=1.25–1.30), 7 or 8 (aHR=1.47, 95% CI=1.44–1.50), or 9 or more (aHR=1.77, 95% CI=1.73–1.82) morbidities (vs <5). Similar findings were observed for HF‐specific hospitalization in those with 5 or 6 (aHR=1.22, 95% CI=1.19–1.26), 7 or 8 (aHR=1.39, 95% CI=1.34–1.44), or 9 or more (aHR 1.68, 95% CI=1.61–1.74) morbidities (vs <5). Consistent findings were seen according to sex, age group, and HF type (preserved, reduced, borderline HF), in the association between categorical burden of multimorbidity and outcomes especially prominent in individuals younger than 65. CONCLUSION: After adjustment, higher levels of multimorbidity predicted worse HF outcomes and may be an important consideration in strategies to improve clinical and person‐centered outcomes. J Am Geriatr Soc 66:2305–2313, 2018. [ABSTRACT FROM AUTHOR]

Background: Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited.Objective: To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice.Design: Retrospective cohort.Setting: National U.S. Food and Drug Administration Sentinel network.Patients: Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014.Measurements: Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score-matched patients starting treatment with dabigatran or warfarin.Results: Among 25 289 patients starting dabigatran therapy and 25 289 propensity score-matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran.Limitation: Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values).Conclusion: In matched adults with atrial fibrillation treated in practice, the incidences of stroke and bleeding with dabigatran versus warfarin were consistent with those seen in trials. The possible relationship between dabigatran and myocardial infarction warrants further investigation.Primary Funding Source: U.S. Food and Drug Administration. [ABSTRACT FROM AUTHOR]

Background: Statin therapy is highly efficacious in the prevention of fatal and nonfatal atherosclerotic events in persons at increased cardiovascular risk. However, its long-term effectiveness in practice depends on a high level of medication adherence by patients.Methods: We identified nondiabetic adults with cardiovascular risk factors between 2008 and 2010 within a large integrated health care delivery system in Northern California. Through 2013, we examined the use and adherence of newly initiated statin therapy based on data from dispensed prescriptions from outpatient pharmacy databases.Results: Among 209,704 eligible adults, 68,085 (32.5%) initiated statin therapy during the follow-up period, with 90.4% receiving low-potency statins. At 12 and 24 months after initiating statins, 84.3% and 80.2%, respectively, were actively receiving statin therapy, but only 42% and 30%, respectively, had no gaps in treatment during those time periods. There was also minimal switching between statins or use of other lipid-lowering therapies for augmentation during follow-up. Age≥50 years, Asian/Pacific Islander race, Hispanic ethnicity, prior myocardial infarction, prior ischemic stroke, hypertension, and baseline low-density lipoprotein cholesterol>100 mg/dL were associated with higher adjusted odds, whereas female gender, black race, current smoking, dementia were associated with lower adjusted odds, of active statin treatment at 12 months after initiation.Conclusions: There remain opportunities for improving prevention in patients at risk for cardiovascular events. Our study identified certain patient subgroups that may benefit from interventions to enhance medication adherence, particularly by minimizing treatment gaps and discontinuation of statin therapy within the first year of treatment. [ABSTRACT FROM AUTHOR]

Background: Ambulatory electrocardiographic (ECG) monitoring is the standard to screen for high-risk arrhythmias. We evaluated the clinical utility of a novel, leadless electrode, single-patient-use ECG monitor that stores up to 14 days of a continuous recording to measure the burden and timing of potentially high-risk arrhythmias.Methods: We examined data from 122,815 long term continuous ambulatory monitors (iRhythm ZIO® Service, San Francisco) prescribed from 2011 to 2013 and categorized potentially high-risk arrhythmias into two types: (1) ventricular arrhythmias including non-sustained and sustained ventricular tachycardia and (2) bradyarrhythmias including sinus pauses >3 s, atrial fibrillation pauses >5 s, and high-grade heart block (Mobitz Type II or third-degree heart block).Results: Of 122,815 ZIO® recordings, median wear time was 9.9 (IQR 6.8-13.8) days and median analyzable time was 9.1 (IQR 6.4-13.1) days. There were 22,443 (18.3%) with at least one episode of non-sustained ventricular tachycardia (NSVT), 238 (0.2%) with sustained VT, 1766 (1.4%) with a sinus pause >3 s (SP), 520 (0.4%) with a pause during atrial fibrillation >5 s (AFP), and 1486 (1.2%) with high-grade heart block (HGHB). Median time to first arrhythmia was 74 h (IQR 26-149 h) for NSVT, 22 h (IQR 5-73 h) for sustained VT, 22 h (IQR 7-64 h) for SP, 31 h (IQR 11-82 h) for AFP, and 40 h (SD 10-118 h) for HGHB.Conclusions: A significant percentage of potentially high-risk arrhythmias are not identified within 48-h of ambulatory ECG monitoring. Longer-term continuous ambulatory ECG monitoring provides incremental detection of these potentially clinically relevant arrhythmic events. [ABSTRACT FROM AUTHOR]

Although heart failure (HF) is a syndrome with important differences in response to therapy by left ventricular ejection fraction (LVEF), existing risk stratification models typically group all HF patients together. The relative importance of common predictor variables for important clinical outcomes across strata of LVEF is relatively unknown.We identified all members with HF between 2005 and 2008 from 4 integrated healthcare systems in the Cardiovascular Research Network. LVEF was categorized as preserved (LVEF ≥50% or normal), borderline (41%-49% or mildly reduced), and reduced (40% or moderately to severely reduced). We used Cox regression models to identify independent predictors of death and hospitalization by LVEF category. Among 30 094 ambulatory adults with HF, mean age was 74 years and 46% were women. LVEF was preserved in 49.5%, borderline in 16.2%, and reduced in 34.3% of patients. During a median follow-up of 1.8 years (interquartile range, 0.8-3.1), 8060 (26.8%) patients died, 8108 (26.9%) were hospitalized for HF, and 20 272 (67.4%) were hospitalized for any reason. In multivariable models, nearly all tested covariates performed similarly across LVEF strata for the outcome of death from any cause, as well as for HF-related and all-cause hospitalizations.We found that in a large, diverse contemporary HF population, risk assessment was strikingly similar across all LVEF categories. These data suggest that, although many HF therapies are uniquely applied to patients with reduced LVEF, individual prognostic factor performance does not seem to be significantly related to level of left ventricular systolic function. [ABSTRACT FROM AUTHOR]

Background: There is scant evidence on the effect that chronic kidney disease (CKD) confers on clinically meaningful outcomes among patients with heart failure with preserved left ventricular ejection fraction (HF-PEF).Methods and Results: We identified a community-based cohort of patients with HF. Electronic medical record data were used to divide into HF-PEF and reduced left ventricular EF on the basis of quantitative and qualitative estimates. Level of CKD was assessed by estimated glomerular filtration rate (eGFR) and by dipstick proteinuria. We followed patients for a median of 22.1 months for outcomes of death and hospitalization (HF-specific and all-cause). Multivariable Cox regression estimated the adjusted relative-risk of outcomes by level of CKD, separately for HF-PEF and HF with reduced left ventricular EF. We identified 14 579 patients with HF-PEF and 9762 with HF with reduced left ventricular EF. When compared with patients with eGFR between 60 and 89 mL/min per 1.73 m(2), lower eGFR was associated with an independent graded increased risk of death and hospitalization. For example, among patients with HF-PEF, the risk of death was nearly double for eGFR 15 to 29 mL/min per 1.73 m(2) and 7× higher for eGFR<15 mL/min per 1.73 m(2), with similar findings in those with HF with reduced left ventricular EF.Conclusions: CKD is common and an important independent predictor of death and hospitalization in adults with HF across the spectrum of left ventricular systolic function. Our study highlights the need to develop new and effective interventions for the growing number of patients with HF complicated by CKD. [ABSTRACT FROM AUTHOR]