Background The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in ...patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial. Methods We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non–central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding. Results The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio HR 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients. Conclusions and Relevance The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF.
Background Oral anticoagulation (OAC) therapy reduces the risk of thromboembolic events associated with atrial fibrillation (AF), yet a substantial proportion of patients with AF are not prescribed ...OAC. The aim of this study is to describe the frequencies of and factors associated with OAC contraindications in contemporary clinical practice. Methods We analyzed data from the ORBIT-AF study, a national, prospective, outpatient registry of incident and prevalent AF. Oral anticoagulation contraindications were uniformly collected at enrollment by site personnel using a predefined list. Baseline patient and provider characteristics were compared between participants with and without documented OAC contraindications. Results From June 2010 to August 2011, 10,130 patients 18 years or older with electrocardiographically documented AF were enrolled at 176 practices. Of these, 1,330 (13.1%) had contraindications documented at the baseline visit: prior bleed (27.7%), patient refusal/preference (27.5%), high bleeding risk (18.0%), frequent falls/frailty (17.6%), need for dual antiplatelet therapy (10.4%), unable to adhere/monitor warfarin (6.0%), comorbid illness (5.3%), prior intracranial hemorrhage (5.0%), allergy (2.4%), occupational risk (0.8%), pregnancy (0.2%), and other (12.6%). Among patients with reported contraindications, 30.3% were taking warfarin or dabigatran, as compared with 83.0% of those without reported contraindications. Besides “patient refusal/preference,” being labeled as having frequent falls or being frail was associated with the lowest OAC use among patients with high stroke risk. Conclusions Contraindications to OAC therapy among patients with AF are common but subjective. Many patients with reported contraindications were receiving OAC, suggesting that the perceived benefit outweighed the potential harm posed by the relative contraindication.
ABSTRACT This is a supplement to the Letter of Singer et al., in which we demonstrated a rapid algorithm for obtaining joint 3D estimates of sky location and luminosity distance from observations of ...binary neutron star mergers with Advanced LIGO and Virgo. We argued that combining the reconstructed volumes with positions and redshifts of possible host galaxies can provide large-aperture but small field of view instruments with a manageable list of targets to search for optical or infrared emission. In this Supplement, we document the new HEALPix-based file format for 3D localizations of gravitational-wave transients. We include Python sample code to show the reader how to perform simple manipulations of the 3D sky maps and extract ranked lists of likely host galaxies. Finally, we include mathematical details of the rapid volume reconstruction algorithm.
A prospective observational cohort study.
To assess long-term outcomes of patients with lumbar spinal stenosis treated surgically or nonsurgically.
The relative benefit of various treatments for ...lumbar spinal stenosis is uncertain. Surgical treatment has been associated with short-term improvement, but recurrence of symptoms has been documented. Few studies have compared long-term outcomes of surgical and nonsurgical treatments.
Patients recruited from the practices of orthopaedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine had baseline interviews with follow-up questionnaires mailed at regular intervals over 10 years. Clinical data were obtained at baseline from a physician questionnaire. Most patients initially undergoing surgery had a laminectomy without fusion performed. Outcomes including patient-reported symptoms of leg and back pain, functional status, and satisfaction were assessed at 8- to 10-year follow-up. Primary analyses were based on initial treatment received with secondary analyses examining actual treatment received by 10 years.
Of 148 eligible consenting patients initially enrolled, 105 were alive after 10 years (67.7% survival rate). Among surviving patients, long-term follow-up between 8 and 10 years was available for 97 of 123 (79%) patients (including 11 patients who died before the 10-year follow-up but completed a 8 or 9 year survey); 56 of 63 (89%) initially treated surgically and 41 of 60 (68%) initially treated nonsurgically. Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically. Outcomes at 1 and 4 years favored initial surgical treatment. After 8 to 10 years, a similar percentage of surgical and nonsurgical patients reported that their low back pain was improved(53% vs. 50%, P = 0.8), their predominant symptom (either back or leg pain) was improved (54% vs. 42%, P = 0.3), and they were satisfied with their current status (55% vs. 49%, P = 0.5). These treatment group findings persisted after adjustment for other determinants of outcome in multivariate models. However, patients initially treated surgically reported less severe leg pain symptoms and greater improvement in back-specific functional status after 8 to 10 years than nonsurgically treated patients. By 10 years, 23% of surgical patients had undergone at least one additional lumbar spine operation, and 39% of nonsurgical patients had at least one lumbar spine operation. Patients undergoing subsequent surgical procedures had worse outcomes than those continuing with their initial treatment. Outcomes according to actual treatment received at 10 years did not differ because individuals undergoing additional surgical procedures had worse outcomes than those continuing with their initial treatment.
Among patients with lumbar spinal stenosis completing 8- to 10-year follow-up, low back pain relief, predominant symptom improvement, and satisfaction with the current state were similar in patients initially treated surgically or nonsurgically. However, leg pain relief and greater back-related functional status continued to favor those initially receiving surgical treatment. These results support a shared decision-making approach among physicians and patients when considering treatment options for lumbar spinal stenosis.
The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation ...requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity.
To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage.
Case-control study.
Academic medical center.
170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation.
The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use.
Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 95% CI, 1.3 to 4.7; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 CI, 2.3 to 9.4; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 CI, 0.8 to 2.2).
Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder.
The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.
The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may ...provide more consistent and predictable anticoagulation than warfarin.
In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism.
In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval CI, 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.
In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and ...Embolism Trial in Atrial Fibrillation).
The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin.
The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model.
The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk.
Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767).
Electronic health record (EHR)‐discontinuity, i.e., having medical information recorded outside of the study EHR system, is associated with substantial information bias in EHR‐based comparative ...effectiveness research (CER). We aimed to develop and validate a prediction model identifying patients with high EHR‐continuity to reduce this bias. Based on 183,739 patients aged ≥65 in EHRs from two US provider networks linked with Medicare claims data from 2007–2014, we quantified EHR‐continuity by mean proportion of encounters captured (MPEC) by the EHR system. We built a prediction model for MPEC using one EHR system as training and the other as the validation set. Patients with top 20% predicted EHR‐continuity had 3.5–5.8‐fold smaller misclassification of 40 CER‐relevant variables, compared to the remaining study population. The comorbidity profiles did not differ substantially by predicted EHR‐continuity. These findings suggest that restriction of CER to patients with high predicted EHR‐continuity may confer a favorable validity to generalizability trade‐off.
Diabetes is a well-established risk factor for thromboembolism in patients with atrial fibrillation (AF), but less is known about how diabetes influences outcomes among AF patients.
This study ...assessed whether symptoms, health status, care, and outcomes differ between AF patients with and without diabetes.
The cohort study included 9,749 patients from the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, a prospective, nationwide, outpatient registry of patients with incident and prevalent AF. Outcomes included symptoms, health status, and AF treatment, as well as 2-year risk of death, hospitalization, thromboembolic events, heart failure (HF), and AF progression.
Patients with diabetes (29.5%) were younger, more likely to have hypertension, chronic kidney disease, HF, coronary heart disease, and stroke. Compared to patients without diabetes, patients with diabetes also had a lower Atrial Fibrillation Effects on Quality of Life score of 80 (interquartile range IQR: 62.5 to 92.6) versus 82.4 (IQR: 67.6 to 93.5; p = 0.025) and were more likely to receive anticoagulation (p < 0.001). Diabetes was associated with higher mortality risk, including overall (adjusted hazard ratio aHR: 1.63; 95% confidence interval CI: 1.04 to 2.56, for age <70 years vs. aHR: 1.25; 95% CI: 1.09 to 1.44, for age ≥70 years) and cardiovascular (CV) mortality (aHR: 2.20; 95% CI: 1.22 to 3.98, for age <70 years vs. 1.24; 95% CI: 1.02 to 1.51 for age ≥70 years). Diabetes conferred a higher risk of non-CV death, sudden cardiac death, hospitalization, CV hospitalization, and non-CV and nonbleeding-related hospitalization, but no increase in risks of thromboembolic events, bleeding-related hospitalization, new-onset HF, and AF progression.
Among AF patients, diabetes was associated with worse AF symptoms and lower quality of life, and increased risk of death and hospitalizations, but not thromboembolic or bleeding events.
Abstract We investigated stroke outcomes in normal weight (body mass index BMI 18.50-24.99 kg/m2 ), overweight (BMI 25.00-29.99 kg/m2 ), and obese (BMI ≥30 kg/m2 ) patients with AF treated with ...rivaroxaban and warfarin. We compared the incidence of stroke and systemic embolic events (SEE) as well as bleeding events in normal weight (n=3289), overweight (n=5535), and obese (n=5206) patients in a post-hoc analysis of the ROCKET AF trial. Stroke and SEE rates per 100 patient-years were 2.93 in the normal weight group (reference group), 2.28 in the overweight group (adjusted hazard ratio HR 0.81, 95% confidence interval CI: 0.66-0.99, p=0.04), and 1.88 in the obese group (adjusted HR 0.69, 95% CI: 0.55-0.86, p<0.001). The risk of stroke was statistically significantly lower for obese patients with BMI ≥35 compared with normal weight patients in both the rivaroxaban and warfarin groups (rivaroxaban: HR 0.62, 95% CI: 0.40-0.96, p=0.033; warfarin: HR 0.48, 95% CI: 0.31-0.74, p<0.001). In conclusion, among patients with AF treated with anticoagulant therapy, increased BMI was associated with decreased stroke risk. Warfarin and the novel anticoagulant rivaroxoban are effective in stroke prevention in all sub-groups of obese patients.
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