Prevalence of co-existing autoimmune disease in juvenile idiopathic arthritis: a cross-sectional study.

BACKGROUND: Many autoimmune diseases share common pathogenic mechanisms, cytokine pathways and systemic inflammatory cascades; however, large studies quantifying the co-existence of autoimmune diseases in patients with juvenile idiopathic arthritis (JIA) have not been conducted. METHODS: We performed a cross-sectional study using two United States administrative healthcare claims databases (Truven Health MarketScan® Commercial Database and IMS PharMetrics database) to screen for the prevalence of multiple autoimmune diseases in patients with JIA and in a control group with attention deficit hyperactivity disorder (ADHD). Patients with a diagnosis code for JIA or ADHD between January 1, 2006 and September 30, 2017 were separated into two age cohorts (< 18 and ≥ 18 years) and matched (maximum 1:5) based on age, sex, number of medical encounters, and calendar year of diagnosis. The prevalence rates of 30 pre-specified autoimmune diseases during the 12-month periods before and after diagnosis were compared. RESULTS: Overall, 29,215 patients with JIA and 134,625 matched control patients with ADHD were evaluated. Among patients in the MarketScan database, 28/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 years and 29/30 were more prevalent in patients aged ≥ 18 years when compared with a matched cohort of patients with ADHD. In the PharMetrics database, 29/30 and 30/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 and ≥ 18 years, respectively, compared with a matched cohort of patients with ADHD. Among patients with JIA aged < 18 years, the greatest odds ratios (ORs) were seen for Sjögren's syndrome/sicca syndrome and uveitis. Among patients aged ≥ 18 years in the MarketScan database, the greatest ORs were recorded for uveitis. Data from the PharMetrics database indicated that the greatest ORs were for uveitis and chronic glomerulonephritis. CONCLUSIONS: Patients with JIA are more likely to have concurrent autoimmune diseases than matched patients with ADHD. Having an awareness of the co-existence of autoimmune diseases among patients with JIA may play an important role in patient management, treatment decisions, and outcomes. TRIAL REGISTRATION: Not applicable.

Discontinuation risk comparison among 'real-world' newly anticoagulated atrial fibrillation patients: Apixaban, warfarin, dabigatran, or rivaroxaban.

Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran, or rivaroxaban. This retrospective cohort study evaluated newly-anticoagulated NVAF patients in the MarketScan® data population from 01/01/2012 through 12/31/2014. Discontinuation was defined as a lack of subsequent prescription of the index drug within 30 days after the last supply day of the last prescription. A Cox model was used to estimate the hazard ratio (HR) of discontinuation, adjusted for age, sex, and comorbidities. Among 45,361 eligible NVAF patients, 15,461 (34.1%) initiated warfarin; 7,438 (16.4%) apixaban; 4,661 (10.3%) dabigatran; and 17,801 (39.2%) initiated rivaroxaban treatment. Compared to warfarin, patients who initiated dabigatran (adjusted HR [aHR]: 0.84, 95% confidence interval [CI]: 0.80-0.87, P<0.001), rivaroxaban (aHR: 0.70, 95% CI: 0.68-0.73, P<0.001), or apixaban (aHR: 0.57, 95% CI: 0.55-0.60, P<0.001) were 16%, 30%, and 43% less likely to discontinue treatment, respectively. When compared to apixaban, patients who initiated dabigatran (aHR: 1.46, 95% CI: 1.38-1.54, P<0.001) or rivaroxaban (aHR: 1.23, 95% CI: 1.17-1.28, P<0.001) were more likely to discontinue treatment. Among newly-anticoagulated NVAF patients in the real-world setting, initiation on rivaroxaban, dabigatran, or apixaban was associated with a significantly lower risk of discontinuation compared to warfarin. When compared to apixaban, patients who initiated treatment with warfarin, dabigatran, or rivaroxaban were more likely to discontinue treatment.

Prevalence of Co-existing Autoimmune Disease in Rheumatoid Arthritis: A Cross-Sectional Study.

INTRODUCTION: Many autoimmune diseases, including rheumatoid arthritis (RA), share common mechanisms; however, population-based studies of the magnitude of multiple autoimmune diseases in patients with RA have not been performed. METHODS: We conducted a cross-sectional study using a US administrative healthcare thcare claims database to screen for prevalence of multiple autoimmune diseases in patients with RA and osteoarthritis (OA). Each patient diagnosed with RA between January 1, 2006 and September 30, 2014 was age- and sex-matched with five patients with OA. The prevalence of 37 pre-specified autoimmune diseases during the 24-month period before and after RA or OA diagnosis was compared. RESULTS: Overall, 286,601 patients with RA and 992,838 matched patients (from 1,421,624 records) with OA were evaluated. During the baseline period, at least one and more than one autoimmune diseases were identified in 24.3% and 6.0% of patients with RA compared with 10.5% and 1.4% of patients with OA, respectively. Highest prevalence rates for patients with RA were for systemic lupus erythematosus (3.8% versus 0.7% for OA) and psoriatic arthritis (3.2% versus 0.4%). Highest odds ratios (ORs) comparing RA with OA were for the prevalence of ankylosing spondylitis (OR 8.0; 95% CI 7.6, 8.5) and psoriatic arthritis (OR 7.8; 95% CI 7.6, 8.1). CONCLUSION: Patients with RA have more concurrent autoimmune diseases than patients with OA. These data suggest that the interrelationship between RA and other autoimmune diseases, and outcomes associated with the occurrence of multiple autoimmune diseases, may play an important role in disease understanding, management, and treatment decisions. FUNDING: Bristol-Myers Squibb.

Cardiovascular Outcomes Associated with Lowering Low-density Lipoprotein Cholesterol in Rheumatoid Arthritis and Matched Nonrheumatoid Arthritis.

OBJECTIVE: To examine the associations between lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular (CV) outcomes among patients with rheumatoid arthritis (RA) and patients without it. METHODS: Adult patients with RA and 2 age- and sex-matched control cohorts [RA plus general controls (RA/GN), RA plus osteoarthritis (OA) controls (RA/OA)] were identified between January 1, 2007, and December 31, 2011. Patients with a diagnosis of hyperlipidemia who initiated statin therapy without prior CV events were included. Multivariable Cox proportional hazard analyses were used. RESULTS: The study identified 1522 patients with RA with 6511 general controls (RA/GN cohort); and 1746 patients with RA with 2554 OA controls (RA/OA cohort). During followup, mean (SD) LDL-C (mg/dl) was 96.8 (32.7) for RA, 100.1 (35.1) for general controls, and 99.1 (34.3) for OA. The relationship between lowering LDL-C and CV outcomes was similar for both RA and non-RA controls (p for interaction = 0.852 in RA/GN cohort, and p = 0.610 in RA/OA cohort). After adjusting for baseline CV risk factors, lowering LDL-C was associated with a 29%-50% lower risk of CV events (HR [95% CI] = 0.71 [0.57-0.89] in RA/GN, 0.50 [0.43-0.58] in RA/OA). Subgroup analyses showed that lowering LDL-C was associated with a similar degree of reduction of CV events in RA and non-RA controls (HR of 0.67-0.68 for RA, 0.72 for general controls, 0.76 for OA controls). CONCLUSION: Lowering LDL-C levels was associated with reduced CV events. The relationship between lowering LDL-C and CV outcomes in RA was similar to the relationship found in matched general and OA controls.

Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a "real-world" observational study in the United States.

BACKGROUND: Limited data are available about the real-world safety of non-vitamin K antagonist oral anticoagulants (NOACs). OBJECTIVES: To compare the major bleeding risk among newly anticoagulated non-valvular atrial fibrillation (NVAF) patients initiating apixaban, warfarin, dabigatran or rivaroxaban in the United States. METHODS AND RESULTS: A retrospective cohort study was conducted to compare the major bleeding risk among newly anticoagulated NVAF patients initiating warfarin, apixaban, dabigatran or rivaroxaban. The study used the Truven MarketScan(®) Commercial & Medicare supplemental US database from 1 January 2013 through 31 December 2013. Major bleeding was defined as bleeding requiring hospitalisation. Cox model estimated hazard ratios (HRs) of major bleeding were adjusted for age, gender, baseline comorbidities and co-medications. Among 29 338 newly anticoagulated NVAF patients, 2402 (8.19%) were on apixaban; 4173 (14.22%) on dabigatran; 10 050 (34.26%) on rivaroxaban; and 12 713 (43.33%) on warfarin. After adjusting for baseline characteristics, initiation on warfarin [adjusted HR (aHR): 1.93, 95% confidence interval (CI): 1.12-3.33, P=.018] or rivaroxaban (aHR: 2.19, 95% CI: 1.26-3.79, P=.005) had significantly greater risk of major bleeding vs apixaban. Dabigatran initiation (aHR: 1.71, 95% CI: 0.94-3.10, P=.079) had a non-significant major bleeding risk vs apixaban. When compared with warfarin, apixaban (aHR: 0.52, 95% CI: 0.30-0.89, P=.018) had significantly lower major bleeding risk. Patients initiating rivaroxaban (aHR: 1.13, 95% CI: 0.91-1.41, P=.262) or dabigatran (aHR: 0.88, 95% CI: 0.64-1.21, P=.446) had a non-significant major bleeding risk vs warfarin. CONCLUSION: Among newly anticoagulated NVAF patients in the real-world setting, initiation with rivaroxaban or warfarin was associated with a significantly greater risk of major bleeding compared with initiation on apixaban. When compared with warfarin, initiation with apixaban was associated with significantly lower risk of major bleeding. Additional observational studies are required to confirm these findings.

The Association Between Bleeding and the Incidence of Warfarin Discontinuation in Patients with Atrial Fibrillation.

AIM: While bleeding is a well-known complication of warfarin use and is thought to be a contributory cause of treatment discontinuation, studies quantifying this association are limited. The objective of this study was to quantify the association between bleeding events and subsequent warfarin discontinuation in patients with nonvalvular atrial fibrillation (NVAF). METHODS: A nested case-control analysis was conducted within a cohort of patients with NVAF newly treated with warfarin. All patients who discontinued warfarin (at least 60 days from last day of warfarin supply) during follow-up were identified as cases and matched with up to 10 controls on age, sex, and duration of follow-up. The index date was defined as the date of warfarin treatment discontinuation of the cases. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of warfarin treatment discontinuation associated with a bleeding event in the 60 days before the index date. RESULTS: The cohort included 24,243 patients who initiated warfarin treatment, of whom 13,482 discontinued treatment during follow-up (cases). Bleeding was associated with an increased risk of warfarin treatment discontinuation (3.55% vs. 0.85%; OR, 4.31; 95% CI, 3.87-4.81). When including only bleeds as the first listed diagnosis, the unadjusted OR was 4.64 (95% CI, 4.10-5.26), and the adjusted OR was 4.65 (95% CI, 4.10-5.27). CONCLUSIONS: Bleeding was significantly associated with warfarin discontinuation, and thus, the selection of an effective treatment regimen associated with a lower bleeding rate could be a desirable treatment approach.

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

OBJECTIVE: To evaluate associations between achieving guideline-recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. METHODS: Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M-HAQ), the EuroQol 5-domain (EQ-5D; a quality-of-life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. RESULTS: Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM-HAQ -0.047; P = 0.0100) and CDAI ≤2.8 (-0.073; P = 0.0003) but not DAS28-CRP <2.6 (-0.022; P = 0.1735). Target attainment was associated with significantly improved EQ-5D (0.022-0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline-recommended disease targets were 36-45% less likely to be hospitalized (P < 0.0500) and 23-45% less likely to utilize DME (P < 0.0100). CONCLUSION: Attaining recommended target disease-activity measures was associated with enhanced physical functioning and health-related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients.

ASSOCIATION BETWEEN HYPOGLYCEMIA AND FALL-RELATED FRACTURES AND HEALTH CARE UTILIZATION IN OLDER VETERANS WITH TYPE 2 DIABETES.

OBJECTIVE: To examine the association between hypoglycemia and fall-related outcomes in older patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective cohort study used electronic medical records of T2DM patients (≥65 years) from the Veterans Integrated Service Network 16 (VISN 16) data warehouse (01/01/2004-06/30/2010). Patients in nonhypoglycemia group (non-HG) were 1:1 randomly matched with patients in hypoglycemia group (HG) by age (±5 years), sex, race, and medical center location. Fall-related events (i.e., fractures and head injuries) were identified, with a fall being the external cause within ±2 days. McNemar tests and generalized estimating equation (GEE) models were used to compare fall-related events in the 1-year outcome period after the index date (i.e., date of first hypoglycemic episode). We also examined fall-related healthcare utilization. RESULTS: A total of 4,215 patients in each group were studied, with the mean age of 76.5 years (SD: 5.85). The mean Charlson comorbidity index (CCI) scores were 5.73 (SD: 2.95) in the HG and 4.34 (SD: 2.40) in the non-HG. The HG had significantly higher rates of fall-related events than non-HG, 27 (0.64%) versus 1 (0.02%) and 89 (2.11%) versus 21 (0.50%) events within 30 days and 1 year, respectively. GEE models confirmed the elevated risk of fall-related events after controlling for sociodemographic and clinical characteristics, comorbidities, and medication use (adjusted odds ratio [aOR]: 2.70; 95% confidence interval [CI]: 1.64-4.47). The HG patients were more likely to have emergency department (ED) visits, hospital admissions, and long-term care placement compared to their counterparts. CONCLUSION: Hypoglycemia is associated with worse fall-related outcomes among the elderly veterans.

Traditional Cardiovascular Disease Risk Factor Management in Rheumatoid Arthritis Compared to Matched Nonrheumatoid Arthritis in a US Managed Care Setting.

OBJECTIVE: To compare traditional cardiovascular (CV) risk factor management among patients with rheumatoid arthritis (RA) to that of matched non-RA controls within a large US managed care setting. METHODS: Adult patients with RA and age- and sex-matched general population (general controls) or osteoarthritis (OA) controls were identified between January 1, 2007 and December 31, 2011. We compared health care utilization, measurement, treatment, and treatment target achievement of traditional CV risk factors among subgroups of CV comorbidity during 1 year of followup between RA and controls. RESULTS: A total of 9,440 RA patients, 31,009 general controls, and 10,352 OA controls were included. The proportions with measurements (blood pressure [BP], low-density lipoprotein [LDL] cholesterol, or hemoglobin A1c ), treatment (antihypertensive, statin, or anti-diabetes mellitus medications), and treatment target achievement were slightly higher in patients with RA compared with general controls. Controlling for other factors, RA patients were more likely to have a measurement of BP (odds ratio [OR] 16.77 [95% confidence interval (95% CI) 10.01-28.08]) or LDL cholesterol (OR 1.25 [95% CI 1.13-1.39]), and to receive antihypertensive (OR 1.84 [95% CI 1.47-2.30]) or anti-diabetic medications (OR 1.26 [95% CI 1.01-1.56]) compared to general controls. RA was not associated with receiving a statin (OR 1.01 [95% CI 0.92-1.12]); however, a target LDL level was more likely to be achieved in RA compared to general controls (OR 1.27 [95% CI 1.17-1.37]) as well as target levels of BP and hemoglobin A1c . These results were consistent with results for OA controls except for a lower probability of receiving a statin in RA compared to OA. CONCLUSION: Traditional CV risk factors in patients with RA were not less aggressively managed compared to non-RA controls.

Association between hypoglycemia and fall-related events in type 2 diabetes mellitus: analysis of a U.S. commercial database.

BACKGROUND: Hypoglycemia is a major barrier to achieving optimal glycemic control and managing diabetes successfully in patients with diabetes. Falls are the most significant consequences caused by hypoglycemia episodes. Both hypoglycemia and falls lead to substantial economic burden on the health care system in the United States. OBJECTIVE: To examine the association of hypoglycemia with fall-related outcomes in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: Records were obtained for T2DM patients (N = 1,147,937) from January 1, 2008, to December 31, 2011. The nonhypoglycemia patients were randomly matched 1:1 by age and gender to the hypoglycemia patients. Fall-related events (composite of fall-related outcomes) were defined using ICD-9-CM codes. Conditional logistic regression models were used to compare the fall-related events within 30 days, 90 days, 180 days, and 365 days between the 2 cohorts. RESULTS: A total of 21,613 hypoglycemia patients were matched with 21,613 nonhypoglycemic patients. Patients with hypoglycemia had higher fall-related events within 30 days, 90 days, 180 days, and 365 days (P less than 0.001 for all frequency differences). Conditional logistic regression analyses showed an elevated risk for fall-related events over 365 days (aOR = 1.95, 95% CI = 1.70-2.24). Subgroup analysis showed elevated risk for patients aged less than 75 years and ≥ 75 years. Elevated risks were also seen for individual fall-related outcomes of fractures, head injuries, long-term care placement, and hospital admissions. CONCLUSIONS: The risk of fall-related events over 365 days increased 2-fold among elderly patients with diabetes who experienced hypoglycemia.

Venous thromboembolism prophylaxis and clinical consequences in medically ill patients.

The objective of this study was to examine venous thromboembolism (VTE) prophylaxis use, risk reduction, and readmission in medically ill patients during hospitalization and after discharge. This 5-year retrospective study linked outpatient files from MarketScan Commercial and Medicare Supplemental databases. Patients were categorized into prophylaxis and non-prophylaxis groups based on guideline-recommended anticoagulant use from the index date to 180 days posthospital discharge and before the first VTE event date. Outcome variables were VTE events and rehospitalization. Risk adjustment was conducted within the prophylaxis group and between the prophylaxis and non-prophylaxis groups using propensity score matching. Among 4467 patients, 28.99% of the patients (n = 1295) were admitted with cancer, 18.03% (n = 805) with pneumonia, 14.06% (n = 628) with heart failure, 11.06% (n = 494) with stroke, 11.11% (n = 496) with sepsis, 8.08% (n = 361) with infectious diseases, 5.6% (n = 250) with severe respiratory disorders, 1.81% (n = 81) with inflammatory bowel disease, 1.05% (n = 47) with obesity, 0.20% (n = 9) with neurologic disorders, and 0.02% (n = 1) with acute rheumatic fever. Among those with 180-day continuous enrollment after the index date (n = 3511), 51.81% (n = 1819) received anticoagulant therapy only, 2.48% (n = 87) received mechanical compression treatment only (stocking or pneumatic compression), and 4.41% (n = 155) received both during hospitalization. Anticoagulant therapy rates ranged from 88.64% (obesity) to 32.39% (inflammatory bowel disease). Among anticoagulant therapy patients, 740 patients (40.68%) received low-molecular weight heparin only and 806 patients (44.31%) received unfractionated heparin. After risk adjustment, compared with patients without VTE prophylaxis, anticoagulant prophylaxis patients had lower VTE (3.62% vs. 4.27%, P < 0.04) and readmission rates (24.22% vs. 27.95%, P < 0.02) during the 6 months post-index hospital admission. In conclusion anticoagulant prophylaxis is underutilized and is associated with reduced VTE risk and a decrease in rehospitalizations for medically ill patients.

Adverse events in patients with liver cancer.

This study aimed to further the understanding of the incidence of adverse events (AEs) in a population-based representative liver cancer population where there is currently a lack of knowledge. We carried out a retrospective cohort study using data from an administrative claims database between 1 January 2004 and 31 December 2010. Patients were included in the study if they had at least one primary liver cancer diagnosis [International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM): 155.0] and a metastatic diagnosis [ICD-9-CM: 196.x, 197.x (except 197.7), 198.x or 199.0]. We estimated the incidence rate (IR) and 95% confidence interval (CI) for each AE under study. Of the patients identified, 1292 fulfilled the inclusion and exclusion criteria. The most common AEs were nausea and vomiting (IR=878.5/1000 person-years; 95% CI=799.5-963.1). Other common AEs were hypertension (IR=648.7/1000 person-years; 95% CI=569.2-736.1) and hemorrhage (IR=580.0/1000 person-years; 95% CI=518.6-646.6). The least common AEs were rare dermatologic diseases such as Stevens-Johnson syndrome and toxic epidermal necrolysis where no cases were observed. The rates detailed in this analysis are helpful in understanding the benefit risk of treating patients with liver cancer in the real world. Although no formal comparisons were performed, the increased risk of certain events observed in sorafenib-treated patients from this analysis mirrors the risks reported on the label for sorafenib. Therefore, this analysis provided a reasonable assessment of the AEs that patients with liver cancer experience in the real world.

Selected adverse events in cancer patients treated with vascular endothelial growth factor inhibitors.

INTRODUCTION: To evaluate the safety profile of new drugs, it is important to quantify the rates of adverse events (AE). There has been little to no research on the safety of vascular endothelial growth factor (VEGF) inhibitors in population-based settings. The purpose of this study was to further the understanding of the incidence of AEs in a population-based representative cancer population receiving VEGF inhibitors where there currently is a deep lack of knowledge. METHODS: We conducted a retrospective cohort study using data from an administrative claims database between January 1, 2004 and December 31, 2010. Patients were included into the study if they had at least two malignant primary cancer diagnoses codes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 140-209 [not including 196-199.0]) from the same cancer site and a prescription for a VEGF inhibitor. We estimated the incidence rate (IR) and 95% confidence interval (CI) for each adverse event under study. RESULTS: 2326 patients met the inclusion and exclusion criteria. The mean age for the cohort was 57.3 where 79% of the patients were 50 years of age or older. The most common adverse event was nausea and vomiting (IR = 651.7/1000 person-years; 95% CI = 589.7-718.4). Other common adverse events were hypertension (IR = 452.9/1000 person-years; 95% CI = 394.9-517.1) and hemorrhage (IR = 375.2/1000 person-years; 95% CI = 332.2-422.3). The least common adverse events were rare dermatologic diseases such as Stevens-Johnson syndrome and toxic epidermal necrolysis where no cases were observed. CONCLUSIONS: The rates detailed in this analysis are helpful in understanding the benefit risk of VEGF inhibitors as they are prescribed in the real world. Although no formal comparisons were conducted, the VEGF inhibitors evaluated in this study appeared to have overlapping toxicity profiles; however, the manner in which these AEs are listed in the prescribing information was not always consistent.

Enoxaparin dosing after discharge from US hospitals in patients with total knee replacement.

BACKGROUND: Prophylaxis for venous thromboembolism after total knee replacement (TKR) is standard of care. Two enoxaparin regimens are approved for thromboprophylaxis, one in the United States (30 mg twice daily [bid]) and another in the rest of the world (40 mg once daily [qd]). Data on frequency of utilization of these 2 regimens at discharge from US hospitals after TKR are not available. METHODS: We conducted a retrospective/descriptive analysis of the PharMetrics claims database to estimate the frequency of utilization of enoxaparin 40 mg qd compared to 30 mg bid after discharge for TKR from US hospitals. RESULTS: Of the 44 552 TKR patients identified, 7198 had an outpatient claim for enoxaparin within 14 days postoperatively. The 40 mg strength of enoxaparin was prescribed more commonly (~51%) than the 30 mg strength (~46%). CONCLUSIONS: Enoxaparin 40 mg qd is prescribed in approximately the same proportion of patients as the current Food and Drug Administration-approved regimen of 30 mg bid.

Cost of Heart Failure in Patients Receiving beta-Blockers and Angiotensin-Converting Enzyme Inhibitors.

OBJECTIVE: Numerous studies support the benefit of beta-blockers and angiotensin-converting enzyme inhibition (ACE-I) in the management of heart failure. However, the real-world cost of heart failure in patients who take these medications is not well documented; furthermore, it is unclear if heart failure costs remain significant when current, appropriately aggressive care is delivered. DESIGN: This study describes 1-year medical costs in patients hospitalised for heart failure who received these therapies, alone or in combination. METHODS: The study population was derived from 2.5 million patients with at least 3 years' continuous eligibility in Pharmetrics((R)), an integrated claims and pharmacy database on approximately 25 million covered lives from 40 US health plans. The enrolment period was from 1 January 1996 to 31 December 2000. Costs included all recorded payments over a 1-year period. A total of 3073 patients (age >18 years) hospitalised with heart failure were identified (mean [+/- SD] age 72 +/- 13 years; 46% female). RESULTS: The 1-year cost was $US16 786 in patients who received neither ACE inhibitors nor beta-blockers as compared with $US19 567, $US22 785 and $US27 078 in patients who received ACE inhibitors, beta-blockers or both drugs at maximum dosage, respectively (p < 0.001) [year of costing 2000]. Follow-up costs were substantial, representing almost twice the initial hospitalisation cost. Adjusted for age, sex, diabetes mellitus, coronary disease, hypertension and renal failure, costs remained significant in heart failure patients who received ACE inhibitors and/or beta-blockers. CONCLUSIONS: The 1-year cost of therapy for patients with heart failure is substantial, and there remains considerable need for more effective therapy to reduce the societal economic burden.

Coronary heart disease in HIV-infected individuals.

It is currently unknown whether there is an increased risk of coronary heart disease (CHD) in patients with HIV infection. In addition, the contribution of antiretroviral therapy (ART) to CHD risk has not been quantified. We reviewed administrative claims data for HIV-infected and -uninfected individuals from the California Medicaid population and compared the incidence of and relative risk (RR) for CHD using log-linear regression analyses between groups. The association between exposure to ART and CHD incidence was also assessed. Of 3,083,209 individuals analyzed, 28,513 were HIV-infected. The incidence of CHD among young men (up to age 34) and women (up to age 44) with HIV infection was significantly higher than that among non-HIV-infected individuals. The covariate-adjusted RR for the development of CHD in individuals receiving ART compared with those not receiving ART was 2.06 (P < 0.001) in HIV-infected individuals aged 18-33 years. There were no statistically significant associations between ART exposure and CHD in other age groups. CHD incidence appears accelerated among young HIV-infected individuals. Strategies to reduce CHD risk should be incorporated into HIV primary care.

Increased use of lipid-lowering therapy in patients receiving human immunodeficiency virus protease inhibitors.

Although human immunodeficiency virus (HIV) protease inhibitors (PIs) improve survival in patients with HIV infection, many patients receiving PIs develop hyperlipidemia, which may increase risk of future coronary events. The purpose of this study was to estimate the changing prevalence of lipid-lowering therapy (LLT) in patients with HIV and to evaluate its association with the use of HIV PIs. This was a cross-sectional study of adults with HIV infection who were registered in the Medicaid of California (MEDI-CAL) administrative claims database. Frequencies of HIV-related and dyslipidemia diagnoses were determined from International Classification of Diseases-9th Edition codes. Use of lipid-lowering and antiretroviral medications was determined by National Drug Codes. Multivariate statistical techniques were used to evaluate trends in use of PIs and lipid-lowering medications from January 1996 to June 2002. The number of HIV-infected patients in MEDI-CAL ranged from 15,764 in 1996 to 13,349 in 2000. The prevalence of LLT use among HIV-infected patients on PIs increased by sixfold (1.7% to 10.6%, p <0.05), and in 2000, exceeded use in the overall MEDI-CAL population (p = 0.09). The increasing rate of LLT in patients taking PIs was greater than in HIV-infected patients not on PIs and in MEDI-CAL (p = 0.002). In multivariate models, increasing age (odds ratio 2.30) and use of PIs (odds ratio 2.08) predicted use of LLT (p <0.001). Thus, in patients taking HIV PIs, use of LLT increased more than sixfold, at a faster rate than in the general population. It has not been proved that use of LLT in HIV-infected patients taking PIs improves survival.

Young HIV-infected adults are at greater risk for medication nonadherence.

This study sought to estimate rates of adherence to nucleoside reverse transcriptase inhibitors (NRTIs) during the first year of administration in the California Medicaid (Medi-Cal) population. A retrospective analysis of pharmacy claims data regarding NRTI prescription refills was employed to estimate adherence and persistence with therapy throughout 1 year in treatment-naive individuals. Adherence was defined as the proportion of days on which drugs were taken during the first 365 days of therapy, and persistence was assessed according to whether prescriptions were refilled over time within a tolerable threshold (60 days). A total of 2614 men and 1174 women exhibited a mean overall adherence rate of 53.0%, and 35.6% of individuals were persistent with therapy throughout the year. No differences in persistence or adherence rates by sex were detected (P =.30). The proportion of individuals with adherence of 80% or better was 26%. Age was found to be significant in adherence and persistence by chi-square examination (P =.001). We conclude that nonadherence can be a critical issue during the first year following initiation of therapy. Comprehensive adherence support programs may be required to maximize adherence, especially among subjects aged 18-24 years, and should be made available early in the course of therapy, or before it is initiated.