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.

Seasonal patterns of Asthma medication fills among diverse populations of the United States.

OBJECTIVE: Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity. METHODS: We conducted a retrospective cohort study of asthmatics 4-50 years of age and enrolled in three diverse health insurance plans. Seasonal patterns of medications were reported by monthly prescription fill rates per 1000 individuals with asthma from 1998 to 2013, and stratified by healthcare plan, sex, and age. RESULTS: There was a distinct and consistent seasonal fill pattern for all asthma medications. The lowest fill rate was observed in the month of July. Fills increased in the autumn and remained high throughout the winter and spring. Compared with the month of May with high medication fills, July represented a relative decrease of fills ranging from 13% (rate ratio, RR: 0.87, 95% confidence interval, 95%CI: 0.72-1.04) for the combination of inhaled corticosteroids (ICS) + long acting beta agonists (LABA) to 45% (RR: 0.55, 95%CI: 0.49-0.61) for oral corticosteroids. Such a seasonal pattern was observed each year across the 16-year study period, among healthcare plans, sexes, and ages. LABA containing control medication (ICS+LABA and LABA) fill rates were more prevalent in older asthmatics, while leukotriene receptor antagonists were more prevalent in the younger population. CONCLUSIONS: A seasonal pattern of asthma medication fill rates likely represents a reactive response to a loss of disease control and increased symptoms. Adherence to and consistent use of asthma medications among individuals who use medications in reaction to seasonal exacerbations might be a key component in reducing the risk of asthma exacerbations.

The Military Health System: Minimizing Disparities in Breast Cancer Treatment.

BACKGROUND: The Military Health System (MHS) is a universal health care system, in which health care disparities are theoretically minimized. This study aimed to identify disparities and assess their impact on the initiation of timely treatment for breast cancer within a universally insured population. METHODS: A retrospective cohort study was performed to evaluate the treatment of female breast cancer patients ≥18 years of age within the MHS from January 1, 2014, to December 31, 2018. Incident breast cancer was defined as ≥2 breast cancer diagnoses without a prior diagnosis of breast cancer during the three continuous years before index diagnosis. Time from index diagnosis to initial treatment was calculated and dichotomized as receiving treatment within a clinically acceptable time course. Poisson regression was used to estimate relative risk (RR) with 95% CIs. RESULTS: Among the 30,761 female breast cancer patients identified in the MHS, only 6% of patients had a prolonged time to initial treatment. Time to initial treatment decreased during the study period from a mean (SD) of 63.2 (152.0) days in 2014 to 37.1 (28.8) days in 2018 (P < 0.0001). Age, region, and military characteristics remained significantly associated with receiving timely treatment even after the adjustment of confounders. Patients 70-79 years old were twice as likely as 18-39 years olds to receive timely treatment (RR: 2.0100, 95% CI, 1.52-2.6563, P < 0.0001). Senior officers and their dependents were more likely to receive timely initial treatment compared to junior enlisted patients and their dependents (RR: 1.5956, 95% CI, 1.2119-2.1005, P = 0.004). CONCLUSIONS: There have been significant improvements in the timely initiation of breast cancer treatment within the MHS. However, demographic and socioeconomic disparities can be identified that affect the timely initiation of therapy.

Cardiovascular outcomes and mortality after initiation of canagliflozin: Analyses from the EASEL Study.

INTRODUCTION: In the EASEL study of patients with type 2 diabetes and high cardiovascular risk, initiation of sodium glucose co-transporter 2 inhibitors (SGLT2i) was associated with lower risk of cardiovascular events and mortality and higher risk of below-knee lower extremity (BKLE) amputation versus non-SGLT2i therapies. This analysis further examined risk of cardiovascular events, cardiovascular and noncardiovascular death and BKLE amputation with the SGLT2i canagliflozin versus non-SGLT2i. METHODS: New user cohorts were constructed from Department of Defense Military Health System patients initiating canagliflozin or non-SGLT2i (4/1/2013-12/31/2016). Propensity score matching (1:1) controlled for imbalances in baseline covariates. Incidence rates, hazard ratios and 95% confidence intervals for time to first composite outcome of all-cause mortality (ACM) and hospitalization for heart failure (HHF), composite major adverse cardiovascular events (MACE) and individual components were evaluated using conditional Cox models. The National Death Index was used to differentiate cardiovascular from noncardiovascular death. The exploratory safety end-point was BKLE amputation. RESULTS: After propensity matching, 15 394 patients with well-balanced baseline covariates were followed for a median of 2.03 years (intent-to-treat). Canagliflozin showed significant benefit for ACM and HHF (P < .0001), MACE (P = .0001), cardiovascular death (P < .0001) and noncardiovascular death (P = .0018). No significant difference in risk of BKLE amputation was observed (P = .20), though few events were observed. Results were generally consistent in on-treatment analyses. CONCLUSIONS: In this high cardiovascular risk cohort studied in routine clinical practice, canagliflozin was associated with lower risk of cardiovascular events, cardiovascular death and all-cause mortality with no significant increase in BKLE amputation risk versus non-SGLT2i.

Sarcoidosis in the United States Military Health System.

Rationale: Sarcoidosis is an inflammatory disorder of unclear etiology with historical significance in the U.S. Department of Defense (DoD). Objectives: This study sought to characterize the sarcoidosis population within the DoD Military Health System (MHS). Methods: Adult patients with sarcoidosis were identified in the DoD MHS database from 01-JAN-2004 through 31-DEC-2013. Patients required ≥3 encounters with a sarcoidosis diagnosis and continuous MHS eligibility. Index was defined as date of first sarcoidosis encounter. Comorbidities were assessed within the pre-index and follow-up periods. Additionally, a subset of sarcoidosis patients was identified as having conditions that can be associated with cardiac sarcoidosis. Measurements and Main Results: The final sarcoidosis cohort was 9,908 patients, 57% female, and had a mean (SD) age of 53.1 (13.6) years. The region with the largest population was the east coast (45.6%). The top 5 pre-index comorbidities were hypertension (51.7%), fatigue (27.0%), anemia (21.4%), diabetes, type II (19.6%), and coronary heart disease (16.5%). Prevalence of the following conditions increased ≥2-fold from pre-index to follow-up: leukocytopenia, pulmonary hypertension, chronic kidney disease, thrombocytopenia, hypercalcemia, venous thromboembolism, congestive heart failure, seizure disorder, stroke/TIA, hypercalciuria, and arthritis. Of the sarcoidosis cohort, 21.8% (n=2,164) were identified as having cardiac conditions that can be associated with cardiac sarcoidosis. The top conditions in this cohort were cardiac arrhythmia (75.6%), congestive heart failure (20.4%), and cardiomyopathy (13.6%). Conclusions: The MHS has a large population of sarcoidosis patients, of which 22% had cardiac conditions that can be associated with granulomatous inflammation of the heart. Prevalence of numerous comorbid conditions increased after sarcoidosis diagnosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 261-267).

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.