Nicholas Sicignano

Characterizing Major Bleeding in Patients With Nonvalvular Atrial Fibrillation: A Pharmacovigilance Study of 27 467 Patients Taking Rivaroxaban

In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to prevent stroke and systemic embolism.

Cardiovascular Outcomes and Risks After Initiation of a Sodium Glucose Cotransporter 2 Inhibitor: Results From the EASEL Population-Based Cohort Study (Evidence for Cardiovascular Outcomes With Sodium Glucose Cotransporter 2 Inhibitors in the Real World)

Background: Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose cotransporter 2 inhibitors (SGLT2i). Trials may have limited ability to address individual end points or safety concerns. Methods: We performed a population-based cohort study among patients with type 2 diabetes mellitus with established cardiovascular disease newly initiated on antihyperglycemic agents within the US Department of Defense Military Health System between April 1, 2013, and December 31, 2016. Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite end point of all-cause mortality and hospitalization for heart failure event, major adverse cardiovascular events (defined as all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke), and individual end points were evaluated using conditional Cox models comparing new SGLT2i users with other antihyperglycemic agents. The exploratory safety end point was below-knee lower extremity amputation. Intent-to-treat and on-treatment analyses were performed. Results: After propensity matching, 25 258 patients were followed for a median of 1.6 years. Compared with non-SGLT2i, initiation of SGLT2i was associated with a lower rate of all-cause mortality and hospitalization for heart failure (1.73 versus 3.01 events per 100 person-years; HR, 0.57; 95% CI, 0.50–0.65) and major adverse cardiovascular events (2.31 versus 3.45 events per 100 person-years; HR, 0.67; 95% CI, 0.60–0.75). SGLT2i initiation was also associated with an ≈2-fold higher risk of below-knee lower extremity amputation (0.17 versus 0.09 events per 100 person-years; HR, 1.99; 95% CI, 1.12–3.51). Because of the disproportionate canagliflozin exposure in the database, the majority of amputations were observed on canagliflozin. Results were consistent in the on-treatment analysis. Conclusions: In this high-risk cohort, initiation of SGLT2i was associated with lower risk of all-cause mortality, hospitalization for heart failure, and major adverse cardiovascular events and higher risk of below-knee lower extremity amputation. Findings underscore the potential benefit and risks to be aware of when initiating SGLT2i. It remains unclear whether the below-knee lower extremity amputation risk extends across the class of medication, because the study was not powered to make comparisons among individual treatments.Background : Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose co-transporter 2 inhibitors (SGLT2i). Trials may have limited ability to address individual endpoints or safety concerns. Methods : We performed a population-based cohort study among type 2 diabetes patients with established cardiovascular disease newly initiated on antihyperglycemic agents (AHAs) within the US Department of Defense Military Health System between 4/1/2013 and 12/31/2016. Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite endpoint of all-cause mortality (ACM) and hospitalization for heart failure (HHF) event, major adverse cardiovascular events (MACE; defined as ACM, nonfatal myocardial infarction, and nonfatal stroke), and individual endpoints were evaluated using conditional Cox models comparing new SGLT2i users with other AHAs. Exploratory safety endpoint was below-knee lower extremity amputation (BKA). Intent-to-treat and on-treatment analyses were performed. Results : After propensity matching, 25,258 patients were followed for a median of 1.6 years. Compared with non-SGLT2i, initiation of SGLT2i was associated with a lower rate of ACM and HHF (1.73 vs. 3.01 events per 100 person-years; HR 0.57; 95% CI: 0.50-0.65) and MACE (2.31 vs. 3.45 events per 100 person-years; HR 0.67, 95% CI: 0.60-0.75). SGLT2i initiation was also associated with a ≈two-fold higher risk of BKA (0.17 vs. 0.09 events per 100 person-years; HR 1.99, 95% CI: 1.12-3.51). Due to the disproportionate canagliflozin exposure in the database, the majority of amputations were observed on canagliflozin. Results were consistent in the on-treatment analysis. Conclusions : In this high-risk cohort, initiation of SGLT2i was associated with lower ACM, HHF, and MACE and higher BKA risk. Findings underscore the potential benefit and risks to be aware of when initiating SGLT2i. It remains unclear whether the BKA risk extends across the class of medication as the study was not powered to make comparisons among individual treatments.

CHA2DS2-VASc Scores and Major Bleeding in Patients With Nonvalvular Atrial Fibrillation Who Are Receiving Rivaroxaban.

Study objective Assessing stroke risk associated with nonvalvular atrial fibrillation depends on the evaluation of patient characteristics and clinical features. Clinicians must determine that the net clinical benefit from anticoagulation therapy outweighs its risk, namely, bleeding. Risk assessment for stroke is commonly performed by calculating a CHA2DS2‐VASc (congestive heart failure/left ventricular dysfunction, hypertension, ≥75 years, diabetes mellitus, previous stroke or transient ischemic attack or thromboembolism, vascular disease, aged 65 to 74 years, sex female) score. It is possible that CHA2DS2‐VASc scores also have a relationship with the incidence of major bleeding. We examined the relationship between CHA2DS2‐VASc scores and major bleeding in rivaroxaban users with nonvalvular atrial fibrillation. Methods Electronic medical records of more than 10 million patients from the Department of Defense Military Health System were queried to identify patients with nonvalvular atrial fibrillation who received rivaroxaban from January 1, 2013, to June 30, 2015. Baseline characteristics of the study population were described by CHA2DS2‐VASc scores and major bleeding status; major bleeding incidence was evaluated by CHA2DS2‐VASc score category and for each CHA2DS2‐VASc component. Results Overall, 44,793 patients met the inclusion criteria for this analysis. The major bleeding incidence rate was 2.84 (95% confidence interval 2.69 to 3.00) per 100 person‐years. The incidence of major bleeding increased from 0.30 to 5.40 per 100 person‐years among patients with a CHA2DS2‐VASc score of 0 to 5 or higher, respectively. Fatal outcomes among patients with major bleeding were positively correlated with CHA2DS2‐VASc scores; patients with higher scores had higher mortality rates. The CHA2DS2‐VASc component with the highest major bleeding incidence was for vascular disease, 5.69 (95% confidence interval 5.18 to 6.24) per 100 person‐years. Conclusion Higher CHA2DS2‐VASc scores are associated with increased incidence of major bleeding in nonvalvular atrial fibrillation patients receiving rivaroxaban.

Predictors of Revision Surgery After Anterior Cruciate Ligament Reconstruction

Background: Arthroscopically assisted anterior cruciate ligament (ACL) reconstruction is a common orthopaedic procedure. Graft failure after reconstruction remains a devastating complication, often requiring revision surgery and less aggressive or modified rehabilitation. Worse functional and patient-reported outcomes are reported compared with primary reconstruction. Moreover, both rates and risk factors for revision are variable and inconsistent within the literature. Purpose: To determine the rate of revision surgery after ACL reconstruction in a large cohort of patients, to assess the influence of patient characteristics on the odds of revision, and to compare revision rates between active-duty military members and non–active-duty beneficiaries. Study Design: Descriptive epidemiology study. Methods: Using administrative data from the Military Health System, a retrospective study was designed to characterize the rate of ACL revision surgery among patients treated within a military facility. All patients ≥18 years at the time of ACL reconstruction were identified using the American Medical Association Current Procedural Terminology (CPT) for ACL reconstruction (CPT code 29888) over 7 years (2005-2011). Revision ACL reconstructions were identified as having ≥2 ACL reconstruction procedure codes on the ipsilateral knee at least 90 days apart. Univariate analysis was performed to calculate odds ratios (ORs) for demographic, perioperative medication use, and concomitant procedure–related risk factors. A multivariate logistic regression model determined risk covariates in the active-duty cohort. Results: The study population consisted of 17,164 ACL reconstructions performed among 16,336 patients, of whom 83.3% were male with a mean ± SD age of 28.9 ± 7.6 years for the nonrevision group, and was predominantly active duty (89.2%). Patients undergoing ACL reconstruction on both knees only contributed their index knee for analyses. There were 587 patients who underwent revision surgery, corresponding to an overall revision rate of 3.6%. The median time from the index surgery to revision surgery was 500 days (interquartile range, 102-2406 days). Revision rates were higher in the active-duty cohort as compared with non–active-duty beneficiaries (3.8% vs 1.8%, respectively; OR, 2.14; 95% CI, 1.49-3.07). Based on multivariate logistic regression in the active-duty cohort, age ≥35 years (OR, 0.44; 95% CI, 0.33-0.58) and concomitant meniscal repair (OR, 0.69; 95% CI, 0.53-0.91) were found to be protective with regard to the odds of revision surgery. Perioperative medication use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR, 1.33; 95% CI, 1.12-1.58; number needed to harm [NNH], 100) and COX-2 inhibitors (OR, 1.31; 95% CI, 1.04-1.66; NNH, 333) was associated with increased odds of revision surgery. No significant findings were detected among sex, race, nicotine use, body mass index, or other concomitant procedures of interest. Conclusion: In this large cohort study, the rate of revision ACL reconstruction was 3.6%, which is consistent with the existing literature. Increased odds of revision surgery among active-duty personnel were associated with the perioperative use of NSAIDs and COX-2 inhibitors. Age ≥35 years and concomitant meniscal repair were found to be protective against ACL revision.

Outcomes of follow-up care after an emergency department visit among pediatric asthmatics in the military health system

Abstract Background and Objectives: Asthma exacerbations frequently trigger emergency department (ED) visits. Guidelines recommend timely follow-up after an ED visit for asthma, however, other studies have questioned the quality of follow-up care and their effect on subsequent ED utilization. We evaluated follow-up care on asthma outcomes in pediatric asthmatics enrolled in the Military Health System (MHS) after an ED visit for asthma. Methods: This retrospective study utilized MHS data to evaluate 2–17-year-old persistent asthmatics with an ED visit for asthma between 2010–2012. Demographics, medication dispensing, and subsequent asthma related ED and hospital utilization were compared between those with or without a 28-day follow-up appointment. Results: 10,460 of 88,837 persistent asthmatics met inclusion criteria for an asthma ED visit. 4,964 (47.5%) had ≥ 1 follow-up visit. In the 29–365 days after their ED visit, 21.1% of the follow-up cohort required an ED re-visit compared to 24.0% of the patients without follow-up. Follow-up care was associated with a reduction in ED re-visits (adjusted hazard ratio 0.86; 95% confidence interval 0.79, 0.93). Controller medications were dispensed to 76.0% of the follow-up cohort within 90 days of their ED visit compared to 49.7% in the group without follow-up. Conclusions: Despite universal access to healthcare, less than half of pediatric MHS asthma patients had follow-up within 28 days of an ED visit. Those with follow-up were more likely to fill a controller medication within 90 days post-ED visit, and less likely to have an asthma ED re-visit in the subsequent year.

Risk Factors for Major Bleeding in Rivaroxaban Users With Atrial Fibrillation.

Rivaroxaban is a novel oral anticoagulant indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Although results from pooled analyses have shown that novel oral anticoagulants are associated with significant reductions in stroke,

Repeat Hospitalizations Predict Mortality in Patients With Heart Failure

INTRODUCTION Heart failure (HF) affects more than 5.1 million Americans and is projected to increase. Understanding the relationship between hospitalization and mortality can help to guide clinical management. The aim of the study is to evaluate the impact of repeat HF hospitalizations on all-cause mortality and to determine risk variables related to patient mortality. MATERIALS AND METHODS Using administrative data from the Military Health System, a cohort of patients with an index admission for HF between 2007 and 2011 was identified. HF hospitalizations were defined as any hospital claim with an International Classification of Diseases, Ninth Revision diagnosis of 428.xx in the primary diagnosis field over the 7-year study period (2007-2013). Patients were subsequently categorized based on total number of HF hospitalizations. A multivariate Cox regression model, adjusting for age, sex, and comorbidities, was used to estimate hazard ratios. Kaplan-Meier survival curves were constructed based on the frequency of HF hospitalizations. RESULTS Of the 51,286 patients admitted for HF, 54.7% were male with a mean (SD) age of 76.3 (10.8) years, and 29,714 died during 135,211 person-years of follow-up. Mean survival time was 2.6, 1.8, 1.5, and 1.3 years after the first, second, third, and fourth hospitalization, respectively. The mortality rate of patients at 30 days and 1 year postindex HF hospitalization was 7.4% and 27.3%, respectively. A history of dementia and chronic kidney disease without dialysis decreased overall survival. CONCLUSIONS Repeat HF hospitalizations remain a strong predictor of mortality for existing patients with HF. As a result, clinicians and patients can individualize the optimal treatment strategy and resources on the basis of the suspected prognosis.

Comparison of the Incidence of Major Bleeding With Rivaroxaban Use Among Nonvalvular Atrial Fibrillation Patients With Versus Without Diabetes Mellitus

Diabetes mellitus (DM) is a common co-morbidity in those with nonvalvular atrial fibrillation (NVAF). Most patients with DM and NVAF have a CHA2DS2-VASc score of ≥1 and should be considered for oral anticoagulation therapy for stroke prevention per treatment guidelines. The most important risk associated with anticoagulation is bleeding, which may be higher in those with NVAF plus DM. Our objective was to evaluate the incidence and characteristics of major bleeding (MB) in rivaroxaban users diagnosed with NVAF, further comparing those with DM versus those without DM, in a real-world clinical setting. Electronic medical records of >10 million patients from the Department of Defense Military Health System were queried to identify rivaroxaban users with NVAF over a 2.5-year period. Major bleeding-related hospitalization was identified by a validated case-finding algorithm. Patient characteristics, incidence and management of MB, and fatal outcomes were assessed by DM status. Of 44,793 rivaroxaban users with NVAF, 12,039 (26.9%) had DM, who were more likely men, younger, with more co-morbidity and higher CHA2DS2-VASc scores. Major bleeding incidence was higher among those with DM compared with those without, 3.68 (95% confidence interval [CI] 3.37 to 4.03) versus 2.51 (95% CI 2.34 to 2.69) per 100 person-years, and intracranial bleeding incidence was 0.19 (95% CI 0.13 to 0.28) versus 0.25 (95% CI 0.20 to 0.31) per 100 person-years. Fatal outcomes were rare for both cohorts, 0.09 per 100 person-years. In conclusion, in this post-marketing study of 44,793 rivaroxaban users with NVAF, patients with DM had more co-morbidities and higher incidence of MB compared with those without DM.

A plateau in new onset type 1 diabetes: Incidence of pediatric diabetes in the United States Military Health System

To describe the incidence and prevalence of type 1 diabetes among pediatric dependents of the US Department of Defense.

Incidence and characteristics of major bleeding among rivaroxaban users with renal disease and nonvalvular atrial fibrillation

Objective Patients with nonvalvular atrial fibrillation (AF) and renal disease (RD) who receive anticoagulation therapy appear to be at greater risk of major bleeding (MB) than AF patients without RD. As observed in past studies, anticoagulants are frequently withheld from AF patients with RD due to concerns regarding bleeding. The objective of this study was to evaluate the incidence and pattern of MB in those with RD, as compared to those without RD, in a population of rivaroxaban users with nonvalvular AF. Methods Electronic medical records of over 10 million patients from the Department of Defense Military Health System were queried to identify rivaroxaban users with nonvalvular AF. A validated algorithm was used to identify MB-related hospitalizations. RD was defined through diagnostic codes present within 6 months prior to the bleeding date for MB cases and end of study participation for non-MB patients. Data were collected on patient characteristics, comorbidities, MB management, and outcomes. Results Overall, 44,793 rivaroxaban users with nonvalvular AF were identified. RD was present among 6,921 patients (15.5%). Patients with RD had a higher rate of MB than those without RD, 4.52 per 100 person-years versus 2.54 per 100 person-years, respectively. The fatal bleeding outcome rate (0.09 per 100 person-years) was identical between those with and without RD. Conclusion In this post-marketing study of 44,793 rivaroxaban users with nonvalvular AF, RD patients experienced a higher MB rate than those without RD. The higher rate of MB among those with RD may be due to the confounding effects of comorbidities.