Erin R. Weeda

External Validation of the Hestia Criteria for Identifying Acute Pulmonary Embolism Patients at Low Risk of Early Mortality

Introduction: There are limited studies evaluating the ability of the Hestia criteria to accurately identify patients with acute pulmonary embolism (PE) at low risk of early mortality. We sought to externally validate the Hestia criteria for predicting in-hospital and 30-day post-PE mortality. Methods: We retrospectively identified consecutive, adult, objectively confirmed PE patients presenting to the emergency department at our institution from November 21, 2010, to January 31, 2014. We ascertained the total number of Hestia criteria met for each patient, calculated the proportion of patients categorized as low risk (ie, no Hestia criteria met), and determined the accuracy of the Hestia criteria for predicting in-hospital and 30-day all-cause mortality. Mortality was determined through Social Security Death Index searches. Results: A total of 577 patients with PE were included, of which 19 (3.3%) and 35 (6.6%) died in hospital or within 30 days of presentation. Both in-hospital and 30-day case fatality rates rose as the number of Hestia criteria increased. One-hundred forty nine (25.8%) patients were classified as low risk for early mortality, and none of these patients died within 30 days (negative predictive values of 100%). The Hestia criteria had excellent sensitivity (100%, 95% confidence interval [CI] = 79.1%-100% and 100%, 95% CI = 87.7%-100%) for predicting in-hospital and 30-day mortality but low specificity (<27.5% for both). The c-statistics for in-hospital and 30-day mortality were 83.5%, 95% CI = 77.1%-89.9% and 78.5%, 95% CI = 71.9%-85.1%. The predictive accuracy of the Hestia criteria remained acceptable in patients >80 years of age, with active cancer or chronic cardiopulmonary disease. Conclusion: The Hestia criteria have an acceptable predictive accuracy to identify patients with PE at low risk for in-hospital or 30-day mortality.

Impact of non-medical switching on clinical and economic outcomes, resource utilization and medication-taking behavior: a systematic literature review

Abstract Objective: To evaluate current knowledge of the impact of non-medical switching on clinical and economic outcomes, resource utilization and medication-taking behavior. Methods: The literature was searched (Medline and Web of Science, January 2000–November 2015) to identify United States’ studies evaluating ≥25 patients and measuring the impact of non-medical switching of drugs (switching to a chemically distinct but similar medication for reasons other than lack of clinical efficacy/response, side effects or poor adherence) on ≥1 clinical, economic, resource utilization or medication-taking behavior outcome. The direction of association between non-medical switching and outcomes was classified as negative or positive if a statistically significant worsening or improvement was reported, or neutral if no significant difference was observed. Results: Twenty-nine studies contributed 96 outcomes (60.4% clinical; 21.9% resource utilization; 13.5% economic; 4.2% medication-taking behavior) within six disease categories (cardio-metabolic, immune-mediated, acid suppression, psychiatric, hormone replacement therapy and pain). The direction of association was more frequently negative (33.3%) or neutral (55.2%) than it was positive (11.5%). Stratified by outcome type, non-medical switching was negatively associated with clinical, economic, healthcare utilization and medication-taking behavior outcomes in 20.7%, 69.2%, 38.1% and 75.0% of cases, respectively; and positively in only 4.8%–17.2% of outcomes subgroups. Of 32 outcomes in patients demonstrating stable/well controlled disease, 68.8% and 31.3% had a negative and neutral direction of association. In patients without demonstrated disease stability, outcomes were negatively, neutrally and positively impacted by non-medical switching in 15.6%, 67.2% and 17.2% of 64 outcomes. Limitations: Our inability to evaluate specific disease state categories and studies/outcomes received equal weight regardless of sample size or magnitude of effect. Conclusions: Non-medical switching was more often associated with negative or neutral effects than positive effects on an array of important outcomes. Among patients with stable/well controlled disease, non-medical switching was associated with mostly negative effects.

Rivaroxaban versus Heparin Bridging to Warfarin Therapy: Impact on Hospital Length of Stay and Treatment Costs for Low-Risk Patients with Pulmonary Embolism.

To compare hospital length of stay (LOS) and hospital treatment costs in low‐risk patients with pulmonary embolism (PE) anticoagulated with rivaroxaban or heparin bridging to warfarin therapy.

Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma: A Systematic Review and Meta-analysis

Importance Combined use of inhaled corticosteroids and long-acting &bgr;-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma. Objective To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma. Data Sources and Study Selection The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017. Two reviewers selected randomized clinical trials or observational studies evaluating SMART vs inhaled corticosteroids with or without a LABA used as the controller therapy and short-acting &bgr;-agonists as the relief therapy for patients aged 5 years or older with persistent asthma and reporting on an outcome of interest. Data Extraction and Synthesis Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs), risk differences (RDs), and mean differences with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength of evidence grading were completed by 2 independent reviewers. Main Outcomes and Measures Asthma exacerbations. Results The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 [65%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 [95% CI, 0.58 to 0.80]; RD, −6.4% [95% CI, −10.2% to −2.6%]) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 [95% CI, 0.60 to 0.98]; RD, −2.8% [95% CI, −5.2% to −0.3%]). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 [range, 4-11] years; 69 [31%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 [95% CI, 0.32 to 0.94]; RD, −12.0% [95% CI, −22.5% to −1.5%]) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 [95% CI, 0.23 to 0.63]; RD, −23.2% [95% CI, −33.6% to −12.1%]). Conclusions and Relevance In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting &bgr;-agonist) and short-acting &bgr;-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited.

Is Rivaroxaban Associated With Shorter Hospital Stays and Reduced Costs Versus Parenteral Bridging to Warfarin Among Patients With Pulmonary Embolism

Objective: We sought to compare the length of stay (LOS) and total costs for patients with pulmonary embolism (PE) treated with either rivaroxaban or parenterally bridged warfarin. Methods: This retrospective claims analysis was performed in the Premier Database from November 2012 to March 2015. Adult patients were included if they had a hospital encounter for PE (an International Classification of Diseases, Ninth Revision code = 415.1×) in the primary position, a claim for ≥1 diagnostic test for PE on day 0 to 2, and initiated rivaroxaban or parenteral anticoagulation/warfarin. Rivaroxaban users (allowing ≤2 days of prior parenteral therapy) were 1:1 propensity score matched to patients receiving parenterally bridged warfarin. Length of stay, total costs, and readmission for venous thromboembolism (VTE) or major bleeding during the same or subsequent 2 months following the index event were compared between cohorts. Analysis restricted to patients with low-risk PE was also performed. Results: Characteristics of the matched PE cohorts (n = 3466 per treatment) were well balanced. Rivaroxaban use was associated with a 1.36-day shorter LOS and

Impact of once- or twice-daily dosing frequency on adherence to chronic cardiovascular disease medications: A meta-regression analysis

2304 reduction in total costs compared to parenterally bridged warfarin (P < .001 for both). Rates of readmission for VTE were similar between cohorts (1.7% vs 1.6%; P = .64). No difference was observed between treatments for readmission for major bleeding (0.2% vs 0.2%; P > .99). In analyses restricted to low-risk patients (n = 1551 per treatment), rivaroxaban was associated with a 1.01-day and a

Rates of major bleeding with rivaroxaban in real-world studies of nonvalvular atrial fibrillation patients: a meta-analysis

1855 reduction in LOS and costs, respectively (P < .001 for both). Rates of readmission were again similar between treatments (P > .56 for all). Conclusion: Rivaroxaban significantly reduced hospital LOS and costs compared to parenterally bridged warfarin, without increasing the risk of readmission.

Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis

BACKGROUND Most cardiovascular diseases require patients to take one or more chronic medications, often administered multiple times daily. We sought to determine the impact of once- vs. twice-daily dosing of chronic cardiovascular disease medication on adherence. METHODS We searched Medline and Embase from 1/1/86 to 10/15/15 for prospective studies electronically measuring adherence for at least four weeks to oral, chronic cardiovascular disease medications taken one to two times daily. Regimen adherence (the proportion of days with the appropriate number of doses taken) and timing adherence (the number of doses taken within an assigned interval divided by the total number of intervals) were outcomes of interest. Meta-regression was performed to assess how dosing frequency, adjusted for study-level covariates, impacted regimen and timing adherence. RESULTS We identified 26 studies that met inclusion criteria. Forty study arms consisting of 1834 patients (range: 12-501) evaluated once-daily dosing and 18 arms consisting of 451 patients (range: 9-82) evaluated twice-daily dosing. Based upon evaluation of the regimen and timing definitions, unadjusted adherence rates were lower for twice-daily (73.8% and 50.4%) than once-daily dosing (83.1% and 74.2%) of chronic cardiovascular disease medications (p≤0.02 for both). Upon meta-regression, adjusted mean percent regimen and timing adherence for twice-daily dosing was 14.2% (95% confidence interval [CI] 6.8-21.7%) and 22.9% (95%CI 13.0-32.8%) worse than once-daily dosing (p≤0.002 for both). CONCLUSION Patients appear to be more adherent to cardiovascular disease medications dosed once-daily compared to twice-daily. Dosing frequency may be a factor for providers to consider when selecting an agent to prescribe.

Should an LDL-Cholesterol Target–Based Approach Be Readopted?:

Abstract Numerous real-world studies estimating major bleeding rates in rivaroxaban patients with nonvalvular atrial fibrillation have been published. We performed a meta-analysis to better quantify the rates of different types of major bleeding seen with rivaroxaban in observational studies. The pooled rates of major bleeding with rivaroxaban were generally low and consistent with those reported in its pivotal randomized controlled trial.

A Review of New Pharmacologic Treatments for Patients With Chronic Heart Failure With Reduced Ejection Fraction

Importance Long-acting muscarinic antagonists (LAMAs) are a potential adjunct therapy to inhaled corticosteroids in the management of persistent asthma. Objective To conduct a systematic review and meta-analysis of the effects associated with LAMA vs placebo or vs other controllers as an add-on therapy to inhaled corticosteroids and the use of a LAMA as add-on therapy to inhaled corticosteroids and long-acting &bgr;-agonists (LABAs; hereafter referred to as triple therapy) vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma. Data Sources MEDLINE, EMBASE, Cochrane databases, and clinical trial registries (earliest date through November 28, 2017). Study Selection Two reviewers selected randomized clinical trials or observational studies evaluating a LAMA vs placebo or vs another controller as an add-on therapy to inhaled corticosteroids or triple therapy vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma reporting on an outcome of interest. Data Extraction and Synthesis Meta-analyses using a random-effects model was conducted to calculate risk ratios (RRs), risk differences (RDs), and mean differences (MDs) with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength-of-evidence grading were completed by 2 independent reviewers. Main Outcomes and Measures Asthma exacerbations. Results Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 [95% CI, 0.48 to 0.92]; RD, −0.02 [95% CI, −0.04 to 0.00]). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 [95% CI, 0.53 to 1.42]; RD, 0.00 [95% CI, −0.02 to 0.02]), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 [95% CI, 0.57 to 1.22]; RD, −0.01 [95% CI, −0.08 to 0.07]). Conclusions and Relevance In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations.