BackgroundFrailty predicts poorer outcomes and decreased anticoagulation use in patients with nonvalvular atrial fibrillation. We sought to assess the effectiveness and safety of apixaban, dabigatran and rivaroxaban versus warfarin in frail nonvalvular atrial fibrillation patients.Methods and ResultsUsing US MarketScan claims data from November 2011 to December 2016, we identified frail oral anticoagulant‐naïve nonvalvular atrial fibrillation patients with ≥12 months of continuous insurance coverage before oral anticoagulant initiation. Frailty status was determined using the Johns Hopkins Claims‐based Frailty Indicator score (≥0.20 indicating frailty). Users of apixaban, dabigatran, or rivaroxaban were separately 1:1 matched to warfarin users via propensity‐scores, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed for up to 2 years or until an event, insurance disenrollment or end of follow‐up. Rates of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In total, 2700, 2784, and 5270 patients were included in the apixaban, dabigatran, and rivaroxaban 1:1 matched analyses to warfarin. At 2 years, neither apixaban nor dabigatran were associated with differences in the hazard of stroke or systemic embolism (HR=0.78; 95% CI=0.46–1.35 and HR=0.94; 0.60–1.45) or major bleeding (HR=0.72; 95% CI=0.49–1.06 and HR=0.87; 95% CI=0.63–1.19) versus warfarin. Rivaroxaban was associated with reduced stroke or systemic embolism at 2 years (HR=0.68; 95% CI=0.49–0.95) without significantly altering major bleeding risk (HR=1.07; 95% CI=0.81–1.32).ConclusionsOur study found rivaroxaban but not apixaban or dabigatran to be associated with reduced SSE versus warfarin in frail nonvalvular atrial fibrillation patients. No direct‐acting oral anticoagulants demonstrated a significant difference in major bleeding versus warfarin.

OBJECTIVES To assess adverse effects of pharmacologic antidepressants for treatment of major depressive disorder (MDD) in adults 65 years of age or older. DESIGN Systematic review and meta‐analysis. SETTING Specialist or generalist outpatient setting, rehabilitation facility, and nursing facilities. PARTICIPANTS Persons 65 years and older with MDD. INTERVENTION Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, or vortioxetine compared with another antidepressant, placebo, or nonpharmacologic therapy. MEASUREMENTS Adverse events, arrhythmias, cognitive impairment, falls, fractures, hospitalization, mortality, QTc prolongation, serious adverse events, and withdrawals due to adverse events. RESULTS Nineteen randomized controlled trials and two observational studies were included. Most studies evaluated treatment of the acute phase (<12 wk) of MDD of moderate severity. SSRIs led to a statistically similar frequency of overall adverse events vs placebo (moderate strength of evidence [SOE]), but SNRIs caused more overall adverse events vs placebo (high SOE) during the acute treatment phase. Both SSRIs and SNRIs led to more study withdrawals due to adverse events vs placebo (SSRIs low SOE; SNRIs moderate SOE). Duloxetine led to a more falls vs placebo (moderate SOE) during 24 weeks of acute and continuation treatment of MDD. CONCLUSION In patients 65 years of age or older with MDD, treatment of the acute phase of MDD with SNRIs, but not SSRIs, was associated with a statistically greater number of overall adverse events vs placebo. SSRIs and SNRIs led to a greater number of study withdrawals due to adverse events vs placebo. Duloxetine increased the risk of falls that as an outcome was underreported in the literature. Few studies examined head‐to‐head comparisons, most trials were not powered to evaluate adverse events, and results of observational studies may be confounded. Comparative long‐term studies reporting specific adverse events are needed to inform clinical decision making regarding choice of antidepressants in this population. J Am Geriatr Soc 67:1571–1581, 2019

Study ObjectivePatients with nonvalvular atrial fibrillation (NVAF) often have multiple comorbidities requiring concomitant medications in addition to their oral anticoagulant (OAC). The objective of this study was to evaluate the impact of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice.DesignRetrospective claims analysis.Data SourceUnited States Truven MarketScan database (November 2012–March 2017).PatientsAdults who were OAC naïve during the 12 months before the day of the first qualifying rivaroxaban or warfarin dispensing (index date); had at least two International Classification of Diseases, Ninth or Tenth Revision diagnosis codes for atrial fibrillation without codes suggesting valvular heart disease; had at least 12 months of continuous insurance coverage prior to the qualifying OAC dispensing; and were experiencing polypharmacy (concomitant prescription claims for five or more unique chronic medication claims) were included. Patients who had concomitant prescription claims for ≥ 10 unique chronic medication claims constituted the substantial polypharmacy cohort used in the secondary analysis. Patients receiving rivaroxaban were propensity‐score matched in a 1:1 ratio to patients receiving warfarin (13,981 patients in each polypharmacy OAC group, and 1765 patients in each substantial polypharmacy OAC group).Measurements and Main ResultsPatients were followed until occurrence of an event (stroke or systemic embolism [SSE] combined [primary effectiveness outcome] or major bleeding [primary safety outcome]), OAC discontinuation or switch (30‐day permissible gap), insurance disenrollment, or end of follow‐up period. Rates of SSE, ischemic stroke, and major bleeding were compared by using Cox regression, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In patients with NVAF taking five or more chronic medications, rivaroxaban was associated with a 34% (95% CI 12–50) and 40% (95% CI 16–57) hazard reduction of SSE and ischemic stroke, respectively. Occurrence of major bleeding was similar between OAC cohorts (HR 1.08, 95% CI 0.92–1.28). A secondary analysis in patients with NVAF with substantial polypharmacy (taking ≥ 10 chronic medications) was also performed. Similar trends in SSE (HR 0.44), ischemic stroke alone (HR 0.62), and major bleeding (HR 1.07) were observed in patients with NVAF who had substantial polypharmacy, although 95% CIs crossed 1.0 for each outcome in this smaller study cohort.ConclusionThis real‐world study suggests that in the setting of polypharmacy and NVAF, rivaroxaban is an effective and safe alternative to warfarin.

Purpose To compare rebleeding rates following treatment of variceal hemorrhage with TIPS alone versus TIPS with variceal embolization in the covered stent-graft era. Methods In this retrospective study, 52 patients (M:F 29:23, median age 52 years) with hepatic cirrhosis and variceal hemorrhage underwent TIPS insertion between 2003 and 2008. Median Child-Pugh and MELD scores were 8.5 and 13.5. Generally, 10-mm diameter TIPS were created using covered stent-grafts (Viatorr; W.L. Gore and Associates, Flagstaff, AZ). A total of 37 patients underwent TIPS alone, while 15 patients underwent TIPS with variceal embolization. The rates of rebleeding and survival were compared. Results All TIPS were technically successful. Median portosystemic pressure gradient reductions were 13 versus 11 mmHg in the embolization and non-embolization groups. There were no statistically significant differences in Child-Pugh and MELD score, or portosystemic pressure gradients between each group. A trend toward increased rebleeding was present in the non-embolization group, where 8/37 (21.6%) patients rebled while 1/15 (6.7%) patients in the TIPS with embolization group rebled (P = 0.159) during median follow-up periods of 199 and 252 days (P = 0.374). Rebleeding approached statistical significance among patients with acute hemorrhage, where 8/32 (25%) versus 0/14 (0%) rebled in the non-embolization and embolization groups (P = 0.055). A trend toward increased bleeding-related mortality was seen in the nonembolization group (P = 0.120).Conclusions TIPS alone showed a high incidence of rebleeding in this series, whereas TIPS with variceal embolization resulted in reduced recurrent hemorrhage. The efficacy of embolization during TIPS performed for variceal hemorrhage versus TIPS alone should be further compared with larger prospective randomized trials.

Amiodarone remains one of the preferred antiarrhythmic medications for patients with advanced heart failure awaiting cardiac transplant. However, the long half-life and rapid redistribution of this agent into donor myocardium expose heart transplant recipients to potential adverse outcomes. In reviewing the current body of literature, we found that pre-operative amiodarone exposure can increase the risk of bradycardia post-transplant; however, this is unlikely to require permanent pacemaker implant. Further, amiodarone has several serious drug-drug interactions with calcineurin inhibitors. Clinicians should therefore consider empiric reduction in initial dosing for tacrolimus or cyclosporine, and carefully monitor blood levels for at least 3 months post-transplant. Although the evidence is conflicting, amiodarone exposure pre-operatively may increase the risk of early graft failure and mortality. Amiodarone use should be minimized whenever possible; if amiodarone cannot practically be discontinued in the pre-transplant phase, judicious monitoring for QTc prolongation and ventricular arrhythmia should be implemented after transplant. As most of the studies included in this review suffered from small sample sizes and limited follow-up, additional research in this area is warranted.

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Patients with elevated inflammatory markers such as hsCRP are at risk for ASVCD events. Several drug classes have shown the ability to decrease hsCRP levels, but the extent to which this reduces ASCVD events in lieu of other drug mechanisms was not clear. Canakinumab specifically targets the inflammatory process in ASCVD and was proven to be effective in preventing ASCVD events in patients with elevated hsCRP levels.

Continuous-flow left ventricular assist devices (CF-LVADs) prolong survival in advanced heart failure patients. Anticoagulation control is critical in CF-LVAD patients due to increased thromboembolic and bleeding risk. We assessed the quality of INR control in CF-LVAD patients measured by time in therapeutic range (TTR). We performed a systematic literature search of MEDLINE and SCOPUS through July 2017 to identify studies evaluating TTR in anticoagulated adult CF-LVAD patients. Data on key characteristics and the TTR end point were then extracted from each study by two investigators using a standardized tool. Using a Hartung-Knapp random effects model, a weighted mean TTR estimate with accompanying 95% confidence interval (CI) was calculated. Statistical heterogeneity was estimated using the I statistic. Five published studies were included. All studies were single-center, retrospective investigations that calculated TTR using the Rosendaal method. Sample sizes ranged from 11 to 115 patients (total of 270 patients) with durations of follow-up ranging from 9 to 76 person-years. On meta-analysis, CF-LVAD patients had a weighted mean TTR of 46.6% (95% CI: 36.0-57.3%, I = 94%). This suggests that warfarin is difficult to manage in CF-LVAD patients, which may contribute to high rates of bleeding and thromboembolic complications.