Background There is a paucity of contemporary data estimating the incidence of major adverse cardiovascular events ( MACE ) in patients with established atherosclerotic disease or multiple risk factors managed in routine practice. We estimated 1‐ and 4‐year incidences of MACE and the association between MACE and vascular beds affected in these patients. Methods and Results Using US IBM MarketScan data from January 1, 2013 to December 31, 2017, we identified patients ≥45 years old with established coronary artery disease, cerebrovascular disease, peripheral artery disease, or the presence of ≥3 risk factors for atherosclerosis during 2013 with a minimum of 4 years of follow‐up. We calculated 1‐ and 4‐year incidences of MACE (cardiovascular death or hospitalization for myocardial infarction or ischemic stroke). A Cox proportional hazards regression model adjusted for age and sex was used to evaluate the association between vascular bed number/location(s) affected and MACE . We identified 1 302 856 patients with established atherosclerotic disease or risk factors for atherosclerosis. Coronary artery disease was present in 16.9% of patients, cerebrovascular disease in 7.6%, peripheral artery disease in 13.6%, and risk factors for atherosclerosis only in 66.0%. The 1‐ and 4‐year incidences of MACE were 1.4% and 6.9%, respectively. At 4 years, MACE was more frequent in patients with atherosclerotic disease in a single (hazard ratio=1.51, 95% CI =1.48–1.55), 2‐(hazard ratio=2.35, 95% CI =2.27–2.44), or all 3 vascular beds (hazard ratio=3.30, 95% CI =2.97–3.68) compared with having risk factors for atherosclerosis. Conclusions Patients with established atherosclerotic disease or who have multiple risk factors and are treated in contemporary, routine practice carry a substantial risk for MACE at 1‐ and 4‐ years of follow‐up. MACE risk was shown to vary based on the number and location of vascular beds involved.

Extended thromboprophylaxis with oral anticoagulation can reduce the risk of symptomatic venous thromboembolism (VTE) in high-risk patients. We sought to estimate the proportion of medically ill patients in the United States who might qualify for extended thromboprophylaxis according to the criteria used in the Medically-Ill Patient Assessment of Rivaroxaban versus Placebo in Reducing Post-Discharge Venous ThromboEmbolism Risk (MARINER) trial. We analyzed 2014 National Inpatient Sample (NIS) data that provide a 20% weighted annual sample of all discharges from US acute-care hospitals. Hospitalizations for acute medically ill patients were identified as those with a primary discharge diagnosis code for heart or respiratory failure, ischemic stroke, infection, or inflammatory diseases. Patients were excluded if they were <40 years old, admitted for surgery or trauma, had a length of stay <3-or >35-days, or were contraindicated to nonvitamin K antagonist oral anticoagulants. The modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE)-VTE score was used to stratify patients' risk for postdischarge VTE, with a score of 2 to 3 suggesting patients were at moderate-and 4 as high-risk. Of the 35 358 810 hospitalizations in the 2014 NIS, 1 849 535 were medically ill patients admitted for heart failure (10.1%), respiratory failure (12.2%), ischemic stroke (8.8%), infection (58.5%), or inflammatory diseases (10.4%). The modified IMPROVE-VTE score classified 1 186 475 (64.1%) of these hospitalizations as occurring in moderate-risk and 407 095 (22.0%) in high-risk patients. This real-world study suggests a substantial proportion of acute medically ill patients might benefit from extended thromboprophylaxis using the modified IMPROVE-VTE score and clinical elements of the MARINER trial.

Objectives We sought to evaluate the effectiveness and safety of rivaroxaban vs apixaban in non‐valvular atrial fibrillation (NVAF) patients with end‐stage renal disease (ESRD) and/or receiving dialysis in routine practice. Methods Using US MarketScan claims data from January 1, 2014, to December 31, 2017, we identified new‐users of rivaroxaban or apixaban during 2015 with at least 12 months of insurance coverage prior to oral anticoagulant (OAC) initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability‐of‐treatment weighting based on propensity scores. Patients were followed for stroke or systemic embolism (SSE) or major bleeding hospitalizations. Cox proportion hazards regression was used to compare rivaroxaban and apixaban. Analyses stratified by age, sex, CHA2DS2‐VASc score, prior stroke, prior bleed, diabetes, and reduced OAC dose were performed. Results We identified 787 rivaroxaban and 1836 apixaban users. Median (25, 75% range) age = 70 (61, 79), CHA2DS2‐VASc score = 3 (2, 4), and follow‐up = 0.87 (0.38, 1.56) years. No differences in the risks of SSE (HR = 1.18, 95% CI = 0.53‐2.63), ischemic stroke (HR = 1.12, 95%CI = 0.45‐2.76), or major bleeding (HR = 1.00, 95% CI = 0.63‐1.58) were observed. No significant interactions were observed upon subgroup analysis. Conclusion In NVAF patients with ESRD and/or receiving dialysis, rivaroxaban and apixaban were associated with similar risks of SSE and major bleeding.

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Objectives: The objectives of this study were to assess comparative effectiveness and harms of opioid and nonopioid analgesics for the treatment of moderate to severe acute pain in the prehospital setting. Methods: We searched MEDLINE V R , Embase V R , and Cochrane Central from the earliest date through May 9, 2019. Two investigators screened abstracts, reviewed full-text files, abstracted data, and assessed study level risk of bias. We performed meta-analyses when appropriate. Conclusions were made with consideration of established clinically important differences and we graded each conclusion's strength of evidence (SOE). Results: We included 52 randomized controlled trials and 13 observational studies. Due to the absence or insufficiency of prehospital evidence we based conclusions for initial analgesia on indirect evidence from the emergency department setting. As

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Introduction A paucity of contemporary data examining bleeding-related hospitalization outcomes in atrial fibrillation (AF) patients exists. Methods Adults in the Nationwide Readmissions Database (January 2016–November 2016) with AF and hospitalized for intracranial hemorrhage (ICH), gastrointestinal, genitourinary, or other bleeding were identified. Association between bleed types and outcomes were assessed using multivariable regression (gastrointestinal defined as referent) and reported as crude incidences and adjusted odds ratios (ORs) or mean differences with 95% confidence intervals (CIs). Results In total, 196,878 index bleeding-related hospitalizations were identified in this AF cohort (CHA2DS2VASc score ≥2 in 95.1%), with 70.8% classified as gastrointestinal. The overall incidences of in-hospital mortality, need for post-discharge out-of-home care, and 30-day readmission were 4.9, 50.8, and 18.2%, respectively. Multivariable regression suggested traumatic and nontraumatic ICHs were associated with higher odds of in-hospital mortality (OR = 3.99, 95% CI = 3.79, 4.19; OR = 13.09, 95% CI = 12.24, 13.99) and need for post-discharge out-of-home care (OR = 2.92, 95% CI = 2.83, 3.01; OR = 2.74, 95% CI = 2.59, 2.90), and increases in mean index hospitalization length-of-stay (8.31 days, 95% CI = 8.03, 8.60, 6.27 days, 95% CI = 5.97, 6.57) versus gastrointestinal bleeding. Genitourinary and other bleeds were associated with lower mortality (OR = 0.37, 95% CI = 0.25, 0.55; OR = 0.59, 95% CI = 0.53, 0.64) and reduced length-of-stays (−2.84 days, 95% CI =  − 2.91, −2.76; −2.06 days, 95% CI =  − 2.11, −2.01) versus gastrointestinal bleeding. Genitourinary bleeds were also associated with a reduced need for post-discharge out-of-home care (OR = 0.86, 95% CI = 0.77, 0.97). Conclusion The burden of bleeding-related hospitalizations was notably driven by relatively rare but severe and life-threatening ICH, and less morbid but more frequent gastrointestinal bleeding. There is need for continued research on bleeding risk factors and mitigation techniques to avoid bleeding-related patient hospitalizations.

Background: There is a paucity of contemporary data assessing the implications of atrial fibrillation (AF) on major adverse cardiovascular events (MACE) in patients with or at high-risk for atherosclerotic disease managed in routine practice. Hypothesis:We sought to evaluate the 4-year incidence of MACE in patients with or at risk of atherosclerotic disease in the presence of AF.Methods: Using US MarketScan data, we identified AF patients ≥45 years old with billing codes indicating established coronary artery disease, cerebrovascular disease, or peripheral artery disease or the presence of ≥3 risk factors for atherosclerotic disease from January 1, 2013 to December 31, 2013 with a minimum of 4-years of available follow-up. We calculated the 4-year incidence of MACE (cardiovascular death or hospitalization with a primary billing code for myocardial infarction or ischemic stroke). Patients were further stratified by CHA 2 DS 2 -VASc score and oral anticoagulation (OAC) use at baseline. Results:We identified 625,951 patients with 4-years of follow-up, of which 77,752 (12.4%) had comorbid AF. The median (25%, 75% range) CHA 2 DS 2 -VASc score was 4 (3, 5) and 64% of patients received an OAC at baseline. The incidence of MACE increased as CHA 2 DS 2 -VASc scores increased (P-interaction<.0001 for all). AF patients receiving an OAC were less likely to experience MACE (8.9% vs 11.6%, P < .0001) including ischemic stroke (5.4% vs 6.7%, P < .0001). Conclusion:Comorbid AF carries a substantial risk of MACE in patients with or at risk of atherosclerotic disease. MACE risk increases with higher CHA 2 DS 2 -VASc scores and is more likely in patients without OAC. K E Y W O R D S atrial fibrillation, established atherosclerotic disease, major adverse cardiovascular events