JaeJin An

Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency

Importance Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events. Objective To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency. Design, Setting, and Participants A retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012. Exposures Any prescribed TRT given by injection, orally, or topically. Main Outcomes and Measures The primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics. Results The cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62-0.84) and combined cardiac events (AMI, SCD, unstable angina, revascularization procedures) (HR, 0.66; 95% CI, 0.60-0.72). Conclusions and Relevance Among men with androgen deficiency, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of 3.4 years.

The Impact of Value‐Based Benefit Design on Adherence to Diabetes Medications: A Propensity Score‐Weighted Difference in Difference Evaluation

OBJECTIVE To evaluate the impact of value-based benefit design (VBBD) on adherence to diabetes medications. METHODS Health Alliance Medical Plans piloted VBBD for diabetes medications for a subgroup of 5400 enrollees in January 2007 while keeping drug benefits unchanged for the remaining plan enrollees. A difference in difference method (DID) was used to evaluate the effect of VBBD based on pharmacy claim data. Patients with unchanged benefits in the same plan were used as the control group. Adherence was measured by the proportion of days covered. Propensity score weighting was used to balance characteristics of the case group and the control group. RESULTS There were 71 patients in the case group and 5037 patients in the control group. The patients in the two groups had comparable characteristics after propensity score weighting. After the implementation of VBBD, the average copayment per 30 days of supply for diabetes medications decreased from

Multiple medication adherence and its effect on clinical outcomes among patients with comorbid type 2 diabetes and hypertension.

15.3 to

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

10.1 for the case group and increased from

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

14.6 to

Stroke and Bleeding Risk Associated With Antithrombotic Therapy for Patients With Nonvalvular Atrial Fibrillation in Clinical Practice

15.1 for the control group. The probability of being adherent increased from 75.3% to 82.6% for the case group and was roughly unchanged from 79.1% to 78.5% for the control group. Propensity score-weighted DID analysis showed that patients with copayment reduction had greater odds of being adherent: odds ratio=1.56, P=0.03, 95% confidence interval 1.04-2.34. CONCLUSION A VBBD program that reduced the copayment for diabetes medications by 36.1% reduced the number of nonadherent patients by 30.0%.

Medication Extraction from Electronic Clinical Notes in an Integrated Health System: A Study on Aspirin Use in Patients with Nonvalvular Atrial Fibrillation

Objective:To investigate multiple medication adherence (MMA) and its impact on microvascular and macrovascular complications using instrumental variables (IVs). Research Design:A retrospective observational study was conducted using administrative claims and electronic medical records from a large physician group in Southern California (N=2334). Subjects:We identified individuals between January 2006 and June 2009 newly starting oral diabetes (DM) or hypertension (HTN) medications with preexisting comorbid HTN or DM prescription history. Measures:MMA was defined as a proportion of days covered where both DM and HTN medications were simultaneously available over a 33-month follow-up period. Microvascular or macrovascular complications included myocardial infarction, stroke, renal failure, and diabetic retinopathy. Multivariable logistic regressions and an IV estimation using physician-related variables were implemented. Results:MMA was supoptimal as the mean (SD) proportion of days covered was 0.53 (0.32). Patients were more adherent to medications for a preexisting condition in comparison with those for the newer disease. Older age, number of index medications [OR (95% CI)=1.36 (1.22–1.52)], receiving care from a physician who prescribed statin more frequently [OR (95% CI)=2.63 (1.67–4.14)], and receiving care from the same physician for both DM and HTN [OR (95% CI)=1.57 (1.08–2.27)] were significant factors of being adherent. Using physician-related IVs, MMA reduced microvascular and macrovascular complications. The increase in MMA from 50% to 80% reduced the average predicted probability of microvascular or macrovascular complication rate by 29.5%. Conclusions:Adherence to medications for DM and HTN were differed and higher MMA reduced microvascular or macrovascular complications when controlling for endogeneity bias.

Warfarin Management and Outcomes in Patients with Nonvalvular Atrial Fibrillation Within an Integrated Health Care System

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.

TIME IN THERAPEUTIC RANGE ≥55% VERSUS <55% ON WARFARIN THERAPY OUTCOMES IN NON-VALVULAR ATRIAL FIBRILLATION PATIENTS

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.

Adherence to the American Diabetes Association retinal screening guidelines for population with diabetes in the United States

Background The quality of antithrombotic therapy for patients with nonvalvular atrial fibrillation during routine medical care is often suboptimal. Evidence linking stroke and bleeding risk with antithrombotic treatment is limited. The purpose of this study was to evaluate the associations between antithrombotic treatment episodes and outcomes. Methods and Results A retrospective longitudinal observational cohort study was conducted using patients newly diagnosed with nonvalvular atrial fibrillation with 1 or more stroke risk factors (CHADS2 ≥1) in Kaiser Permanente Southern California between January 1, 2006 and December 31, 2011. A total of 1782 stroke and systemic embolism (SE) and 3528 major bleed events were identified from 23 297 patients during the 60 021 person-years of follow-up. The lowest stroke/SE rates and major bleed rates were observed in warfarin time in therapeutic range (TTR) ≥55% episodes (stroke/SE: 0.87 [0.71 to 1.04]; major bleed: 4.91 [4.53 to 5.28] per 100 person-years), which was similar to the bleed rate in aspirin episodes (4.95 [4.58 to 5.32] per 100 person-years). The warfarin TTR ≥55% episodes were associated with a 77% lower risk of stroke/SE (relative risk=0.23 [0.18 to 0.28]) compared to never on therapy; and the warfarin TTR <55% and on-aspirin episodes were associated with a 20% lower and with a 26% lower risk of stroke/SE compared to never on therapy, respectively. The warfarin TTR <55% episodes were associated with nearly double the risk of a major bleed compared to never on therapy (relative risk=1.93 [1.74 to 2.14]). Conclusions Continuation of antithrombotic therapy as well as maintaining an adequate level of TTR is beneficial to prevent strokes while minimizing bleeding events.