Eosinophilic gastritis and eosinophilic enteritis (EoG/EoN) are associated with a substantial clinical burden. However, limited information is available regarding the economic burden of EoG/EoN. This study was conducted to compare healthcare resource use (HRU) and costs among patients with EoG/EoN versus without EoG/EoN in the USA. Administrative claims data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits Databases (2009–2019) was used to identify two cohorts of patients. Patients without EoG/EoN were matched 3:1 to patients with EoG/EoN on sex, year of birth, and healthcare plan type. Study measures included demographic characteristics, select comorbidities, all-cause HRU, and costs. Comparisons were made over a 1-year period following EoG/EoN diagnosis for patients with EoG/EoN and an eligible date for patients without EoG/EoN. A total of 2219 patients with EoG/EoN and 6657 patients without EoG/EoN were analyzed. Significantly higher proportions of patients with EoG/EoN versus without EoG/EoN had comorbid conditions. Rates of all-cause HRU were significantly higher among patients with EoG/EoN versus patients without EoG/EoN (adjusted rate ratio [95% confidence interval]: inpatient visits, 6.26 [5.26, 7.46]; outpatient visits, 1.17 [1.16, 1.19]; emergency department visits, 2.11 [1.98, 2.25]; all p < 0.001). Patients with EoG/EoN incurred significantly higher costs versus patients without EoG/EoN (adjusted mean cost difference $31,180; p < 0.001). Cost differences were largely due to outpatient (adjusted mean cost difference $14,018; p < 0.001) and inpatient (adjusted mean cost difference $11,224; p < 0.001) costs. The economic burden associated with EoG/EoN is substantial, with patients with EoG/EoN having a higher rate of HRU and incurring $31,180 more than patients without EoG/EoN on average. Most of the cost difference was attributable to outpatient and inpatient costs. Cost-saving strategies to lower the burden of illness in this patient population are needed.

INTRODUCTION:Limited evidence is available regarding the postdischarge economic and readmission burdens of hyperkalemia. METHODS:Using the IBM MarketScan Commercial and Medicare-Supplemental Claims database (January 1, 2010-December 31, 2014), adult patients with a hospitalization with a hyperkalemia diagnosis (ICD-9-CM 276.7, hyperkalemia cohort) were 1:1 matched with patients with a hospitalization without evidence of hyperkalemia (nonhyperkalemia cohort) on age, chronic kidney disease stage, heart failure, dialysis, renin-angiotensin-aldosterone system inhibitor use, and major diagnostic categories of the hospitalization. All-cause health care costs and health care resource utilization measures were compared between cohorts during the 1-year postdischarge period. Postdischarge readmission and length of stay (LOS) were compared between hyperkalemia-related hospitalizations from the hyperkalemia cohort and matched hospitalizations unrelated to hyperkalemia from the nonhyperkalemia cohort. RESULTS:Patients with hyperkalemia-related hospitalizations (n = 4426) incurred $30,379 (95% confidence interval, $25,423-$35,335) higher 1-year total all-cause costs ($68,861 vs. $38,482) and had higher rates of inpatient admissions (1.0 vs. 0.4), emergency department visits (2.0 vs. 1.2), and outpatient visits (49.6 vs. 39.1) than the nonhyperkalemia cohort during the 1-year postdischarge study period (all P < 0.001). Hyperkalemia-related hospitalizations (n = 5377) were associated with significantly higher readmission rates (within 30 days: 0.15 vs. 0.09; 60 days: 0.25 vs. 0.16; 90 days: 0.36 vs. 0.23; all P < 0.001), longer LOS per readmission (8.1 vs. 7.1 days), and longer total inpatient days (10.5 vs. 5.8 days) compared with hospitalizations unrelated to hyperkalemia (all P < 0.001). Similar trends were observed across comorbidity subgroups. CONCLUSION:Hyperkalemia-related hospitalizations were associated with significant economic and readmission burdens during the 1-year postdischarge period.

Objective:To estimate the prevalence and economic burden of hyperkalemia in the United States (US) Medicare population. Methods:Patients were selected from a 5% random sample of Medicare beneficiaries (01 January 2010-31 December 2014) to estimate the prevalence and economic burden of hyperkalemia. The prevalence for each calendar year was calculated as the number of patients with hyperkalemia divided by the total number of eligible patients per year. To estimate the economic burden of hyperkalemia, patients with hyperkalemia (cases) were matched 1:1 to patients without hyperkalemia (controls) on age group, chronic kidney disease [CKD] stage, dialysis treatment, and heart failure. The incremental 30-day and 1-year resource utilization and costs (2016 USD) associated with hyperkalemia were estimated. Results:The estimated prevalence of hyperkalemia was 2.6-2.7% in the overall population and 8.9-9.3% among patients with CKD and/or heart failure. Patients with hyperkalemia had higher 1-year rates of inpatient admissions (1.28 vs. 0.44), outpatient visits (30.48 vs. 23.88), emergency department visits (2.01 vs. 1.17), and skilled nursing facility admissions (0.36 vs. 0.11) than the matched controls (allp < .001). Patients with hyperkalemia incurred on average $7208 higher 30-day costs ($8894 vs. $1685) and $19,348 higher 1-year costs ($34,362 vs. $15,013) than controls (bothp < .001). Among patients with CKD and/or heart failure, the 30-day and 1-year total cost differences between cohorts were $7726 ($9906 vs. $2180) and $21,577 ($41,416 vs. $19,839), respectively (bothp < .001). Conclusions:Hyperkalemia had an estimated prevalence of 2.6-2.7% in the Medicare population and was associated with markedly high healthcare costs.

INTRODUCTION: Patients with eosinophilic gastritis and/or gastroenteritis (EG/EGE) experience significantly reduced health-related quality of life related to the symptoms and signs of their disease. There is a need to develop a PRO questionnaire for clinical research in EG/EGE. The objectives of this study were to develop a symptom questionnaire (drafted using literature and clinician input to determine preliminary measurement concepts) and then (1) identify, describe, and substantiate signs, symptoms, and impacts of EG/EGE from the perspective of adults with the condition via concept elicitation methods; and (2) evaluate the properties of the questionnaire and make modifications via cognitive debriefing methods. METHODS: Interviews were conducted, transcribed, coded, and analyzed. Eligible adults with EG/EGE first participated in a concept elicitation segment where they described their experiences with EG/EGE, continuing until saturation was achieved, adding symptoms to the draft symptom questionnaire as needed. This was followed by a cognitive debrief to assess the appropriateness of the draft symptom questionnaire, where patients assessed readability, comprehensibility, relevance, and comprehensiveness. The questionnaire was modified based on patient feedback, then re-evaluated to confirm its appropriateness. RESULTS: In total, 16 interviews were conducted and 24 signs and symptoms were reported during concept elicitation. The most frequently reported (Figure 1) were abdominal pain, nausea, diarrhea, vomiting, and abdominal cramping; while abdominal pain, nausea, and diarrhea were the most bothersome to patients. Saturation was achieved after 12 interviews. In the cognitive debriefing, revisions included the addition of a vomiting frequency item and revision of the early satiety item for clarity. Response options were modified to instruct the participants to assess each symptom “at its worst”. For the final version of the EG/EGE-SQ©, participants were able to read, comprehend, and provide appropriate responses, and reported that the resulting questionnaire was comprehensive for their condition. CONCLUSION: The results of this research support the content validity, including comprehensiveness and interpretability, of the EG/EGE-SQ© which offers the potential for use in clinical research to assess symptoms in patients with EG/EGE. Future research is needed to assess its psychometric properties including reliability and validity, responsiveness, and potential for use in pediatric populations.

Introduction: There are limited data on the cost of hyperkalemia. Methods: This retrospective analysis of the Truven MarketScan claims database assessed the economic burden of hyperkalemia among selected adult patients with hyperkalemia and matched controls. Results: A total of 39,626 cases (patients with hyperkalemia) were matched to 39,626 controls (patients without hyperkalemia) based on age, dialysis, chronic kidney disease (CKD) stage, heart failure, and renin-angiotensin aldosterone system inhibitor use. Compared with controls, cases incurred $4128 (95% confidence interval [CI] $3893-$4363) higher 30-day total health care costs ($5994 vs. $1865) and $15,983 (95% CI $15,026-$16,940) higher 1-year costs ($31,844 vs. $15,861). Among 11,221 matched pairs of patients with CKD and/or heart failure, cases incurred $5553 (95% CI $5059-$6047) higher 30-day total health care costs ($8165 vs. $2612) and $24,133 (95% CI $21,748-$26,518) higher 1-year costs ($48,994 vs. $24,861) than controls. The multivariable adjusted 1-year total health care cost difference was $15,606 (95% CI $14,648-$16,576) among all patients and $25,156 (95% CI $23,529-$26,757) among patients with CKD and/or heart failure. Cases had higher resource utilization rates including inpatient admissions (30-day: 0.14 vs. 0.03; 1-year: 0.44 vs. 0.19), outpatient visits (30-day: 3.33 vs. 2.28; 1-year: 26.58 vs. 18.53), and emergency department visits (30-day: 0.16 vs. 0.06; 1-year: 0.86 vs. 0.50) (all P < 0.001). When hospitalized, cases stayed 1.51 days (95% CI 1.22-1.80) longer and were 40% more likely to be readmitted. Conclusion: These data indicate that hyperkalemia is associated with a significant economic burden on afflicted patients and the health care system.

BACKGROUND:PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. METHODS AND RESULTS:These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites). CONCLUSIONS:PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk.

Background— PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. Methods and Results— These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel–Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32–39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11–16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28–0.92) in blacks and 0.82 (95% CI, 0.63–1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48–1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80–1.41 in whites). Conclusions— PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk.

Objectives To describe prophylactic and acute medication treatment patterns, including timing, medication type, and duration of use in migraine patients initiating prophylaxis. Background Patients with migraine can be treated with acute and prophylactic therapies. Current treatment options for migraine prophylaxis are associated with poor tolerability and low adherence and persistence. Methods This retrospective cohort study used the Truven Health Analytics MarketScan ® Research Databases to identify adults in the United States with a migraine diagnosis who initiated migraine prophylactic medication (index event) between January 1, 2008, and December 31, 2011. Prescribed prophylactic medications evaluated included topiramate, beta‐blockers, and tricyclic antidepressants. Patients were required to have 12 months of pre‐ and post‐index continuous enrollment. Patient characteristics, migraine‐specific prescribed prophylactic treatment patterns (including gaps in therapy, treatment switches, and additions of index medications), and prescribed acute medication utilization were assessed. Results The study population comprised 107,122 patients, with 52,275 (49%) initiating topiramate, 22,658 (21%) initiating beta‐blockers, and 32,189 (30%) initiating tricyclic antidepressants. Mean (SD) age was 41 (12) years and 83% were female. Persistence with migraine prophylactic medication was low; 81% of patients had gaps of >90 days in their migraine prophylaxis in the first year. The gap in therapy occurred early in treatment (mean, 95 days), and only 10% of patients restarted prophylactic therapy within that year. Switching from index medication to another prophylactic medication or adding prophylaxis was uncommon (13% and 5%, respectively). One year after initiating prophylaxis, 65% of patients were not receiving any prophylactic therapies. Most patients initiating migraine prophylaxis also utilized acute treatments (81%); opioid use was more frequent than triptan use (53% vs 48%) and was common (40%) among patients without other chronic pain conditions (eg, arthritis, fibromyalgia, and lower back pain). Conclusion Patients with migraine who initiated prophylactic therapy had poor persistence with early gaps in therapy, were unlikely to switch prophylactic treatments, and most discontinued prophylaxis by the end of the first year.

BACKGROUND Hyperkalemia (serum potassium >5.0 mEq/L) may be caused by reduced kidney function and drugs affecting the renin-angiotensin-aldosterone system and is often present in patients with chronic kidney disease (CKD). OBJECTIVE To quantify the burden of hyperkalemia in US Medicare fee-for-service and commercially insured populations using real-world claims data, focusing on prevalence, comorbidities, mortality, medical utilization, and cost. METHODS A descriptive, retrospective claims data analysis was performed on patients with hyperkalemia using the 2014 Medicare 5% sample and the 2014 Truven Health Analytics MarketScan Commercial Claims and Encounter databases. The starting study samples required patient insurance eligibility during ≥1 months in 2014. The identification of hyperkalemia and other comorbidities required having ≥1 qualifying claims in 2014 with an appropriate International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code in any position. To address the differences between patients with and without hyperkalemia, CKD subsamples were analyzed separately. Mortality rates were calculated in the Medicare sample population only. The claims were grouped into major service categories; the allowed costs reflected all costs incurred by each cohort divided by the total number of member months for that cohort. RESULTS The prevalence of hyperkalemia in the Medicare and commercially insured samples was 2.3% and 0.09%, respectively. Hyperkalemia was associated with multiple comorbidities, most notably CKD. The prevalence of CKD in the Medicare and the commercially insured members with hyperkalemia was 64.8% and 31.8%, respectively. After adjusting for CKD severity, the annual mortality rate for Medicare patients with CKD and hyperkalemia was 24.9% versus 10.4% in patients with CKD without hyperkalemia. The allowed costs in patients with CKD and hyperkalemia in the Medicare and commercially insured cohorts were more than twice those in patients with CKD without hyperkalemia. Inpatient care accounted for >50% of costs in patients with CKD and hyperkalemia. CONCLUSION Hyperkalemia is associated with substantial clinical and economic burden among US commercially insured and Medicare populations.

OBJECTIVES:The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol treatment guideline recommends monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. We examined LDL-C reduction and statin adherence among high-risk patients initiating statins in a real-world setting.STUDY DESIGN:Retrospective cohort study.METHODS:The study population included Kaiser Permanente Georgia members (n = 1066) with a history of coronary heart disease or risk equivalent(s) initiating statins in 2011. Percent change in LDL-C was defined using measurements before and 60 to 450 days after statin initiation. Statin adherence was defined by proportion of days covered, categorized as high (≥80%), intermediate (50%-79%), and low (< 50%).RESULTS:Overall, 58.4% of patients failed to achieve a ≥ 30% LDL-C reduction after statin initiation. The prevalences of high, intermediate, and low statin adherence were 41.3%, 23.2%, and 35.6%, respectively. Of patients with high adherence, 42.3% did not achieve a ≥ 30% reduction in LDL-C compared with 54.7% and 79.7% of those with intermediate and low statin adherence, respectively. After multivariable adjustment, and compared with those with high adherence, the risk ratios for not achieving a ≥ 30% LDL-C reduction were 1.31 (95% CI, 1.13-1.52) and 1.88 (95% CI, 1.67-2.11), for those with intermediate and low adherence. Women and African Americans were less likely to have high adherence, whereas having cardiologist visits was associated with high adherence.CONCLUSIONS:In a real-world setting, many patients did not achieve a 30% or larger LDL-C reduction. These data support the ACC/AHA recommendation to monitor LDL-C response among patients initiating statins.

Introduction: Hyperkalemia (HK) is a potentially life-threatening condition known to adversely affect cardiac function, and may cause arrhythmia, myocardial infarction, or stroke. Healthcare costs ...

Biologic therapies are approved for moderate/severe plaque psoriasis. In trials of newer biologics, many patients achieved complete skin clearance. This abstract reports interim Resultsfrom a study examining real-world effectiveness of biologics in psoriasis. This prospective observational study includes adults initiating biologic treatment, or switching to a new biologic, for psoriasis in Europe and the US. Dermatologist evaluation of the Psoriasis Area and Severity Index (PASI) and the patient-reported Psoriasis Symptom Index (PSI] and Dermatology Life Quality Index (DLQI) are collected at baseline, 6 and 12 months after biologic initiation. Endpoints include complete skin clearance (100% improvement in PASI [PASI 100] or PASI=0), PASI 90, PASI 75, PSI and DLQI. Missing data are imputed using the last observation carried-forward. These interim Resultsinclude patients who had the opportunity to complete a 6-month assessment. This interim analysis included 126 patients (69.8% male, mean [SD] age 47.3 [14.3] years, mean [SD] psoriasis duration 17.3 [12.9] years). At baseline, mean (SD) PASI was 14.8 (9.4), and 53.2% patients were biologic-naïve. At 6-months, 17.5% [95% CI: 11.3%, 25.2%] of patients achieved complete skin clearance; fewer than half (48.0% [39.0%, 57.1%]) achieved a PASI 75, 28.0% [20.3%, 36.7%] achieved a PASI 90, and 17.6% [11.4%, 25.4%] a PASI 100. In addition, 16.8% of patients had a PSI of 0 and 23.8% a DLQI of 0 (lower scores indicate fewer psoriasis symptoms and better quality of life). Fewer than 20% of patients achieved complete skin clearance 6 months after initiating a biologic and less than half achieved a 75% improvement in PASI. In addition, more than 75% of patients reported some decrement to quality of life and more than 80% reported psoriasis symptoms. These Resultssuggest that more effective treatments could improve outcomes for many patients with moderate to severe psoriasis.

Previous studies have documented the significant negative effect of asthma and poor control on health care resource use (HRU).1Sullivan P.W. Ghushchyan V.H. Slejko J.F. Belozeroff V. Globe D.R. Lin S.L. The burden of adult asthma in the United States: evidence from the Medical Expenditure Panel Survey.J Allergy Clin Immunol. 2011; 127: 363-369.e3Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 2Sullivan P.W. Slejko J.F. Ghushchyan V.H. Sucher B. Globe D.R. Lin S.L. et al.The relationship between asthma, asthma control and economic outcomes in the United States.J Asthma. 2014; 51: 769-778Crossref PubMed Scopus (69) Google Scholar The extent of the effect is associated with the degree of asthma control. Standardized tools, such as the Asthma Control Questionnaire (ACQ),3Juniper E.F. O'Byrne P.M. Guyatt G.H. Ferrie P.J. King D.R. Development and validation of a questionnaire to measure asthma control.Eur Respir J. 1999; 14: 902-907Crossref PubMed Scopus (1884) Google Scholar have been shown to be valid measures of control. Previous studies examining HRU using validated control measures have typically been conducted in clinical trials or specialty or severe populations not generalizable to the broader persistent asthma population.4Sullivan S.D. Rasouliyan L. Russo P.A. Kamath T. Chipps B.E. TENOR Study GroupExtent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma.Allergy. 2007; 62: 126-133Crossref PubMed Scopus (165) Google Scholar, 5Meltzer E.O. Busse W.W. Wenzel S.E. Belozeroff V. Weng H.H. Feng J. et al.Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.J Allergy Clin Immunol. 2011; 127: 167-172Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar Other studies conducted in real-world settings have used surrogate markers of control (eg, β-agonist use or exacerbations).2Sullivan P.W. Slejko J.F. Ghushchyan V.H. Sucher B. Globe D.R. Lin S.L. et al.The relationship between asthma, asthma control and economic outcomes in the United States.J Asthma. 2014; 51: 769-778Crossref PubMed Scopus (69) Google Scholar, 6Vollmer W.M. Markson L.E. O'Connor E. Frazier E.A. Berger M. Buist A.S. Association of asthma control with health care utilization: a prospective evaluation.Am J Respir Crit Care Med. 2002; 165: 195-199Crossref PubMed Scopus (165) Google Scholar, 7Stempel D.A. McLaughin T.P. Stanford R.H. Fuhlbrigge A.L. Patterns of asthma control: a 3-year analysis of patient claims.J Allergy Clin Immunol. 2005; 115: 935-939Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar Our study aimed to bridge this gap by using a validated measure of asthma control (ACQ-5) in a real-world setting in a general population with persistent asthma. The Observational Study of Asthma Control and Outcomes included a prospective survey and retrospective claims of patients with asthma enrolled in Kaiser Permanente of Colorado (KPCO). Eligible patients received 3 rounds of the same survey during 1 year: April through August 2011, September through December 2011, and March through June 2012. Study variables for this analysis included asthma control measured by using the ACQ-5, exacerbations, HRU, self-reported adherence, and sociodemographic characteristics. In adjusted analyses HRU measures were regressed on ACQ-5 scores (as a continuous variable) by using negative binomial models controlling for fixed effects, age, sex, family income level, race, educational attainment, ethnicity, and smoking status. A more complete description of the methods is available in the Methods section in this article's Online Repository at www.jacionline.org. Fig E1 and Table E1 in this article's Online Repository at www.jacionline.org present the sample disposition and descriptive characteristics. One thousand seven hundred ninety-nine subjects completed all 3 surveys, 387 completed only 2 surveys, and 495 completed only 1 survey. Self-reported adherence to controller medications was substantial (77%). Nineteen percent of subjects reported having an exacerbation requiring the use of oral corticosteroids in the previous 6 weeks. Most ACQ-5 scores in this general population with persistent asthma fell between 0 and 1 (55%) or 1 and 2 (30%, Table I and Fig E2 in this article's Online Repository at www.jacionline.org). Only 10% of subjects with ACQ-5 scores of 0 to 1 reported having an exacerbation compared with 62% of those with ACQ-5 scores of 4 to 5 (Table I and see Fig E3 in this article's Online Repository at www.jacionline.org). Mean unadjusted HRU generally increased with increasing ACQ-5 scores. Inhaled corticosteroid (ICS) prescriptions were higher for higher ACQ-5 scores, whereas adherence was slightly higher.Table IUnadjusted mean exacerbations and HRU by ACQ-5 score (per 4 months)ACQ-5 score = 0-1.0, n = 3654 (55.2%)ACQ-5 score = 1.0-2.0, n = 1984 (30.0%)ACQ-5 score = 2.0-3.0, n = 759 (11.5%)ACQ-5 score = 3.0-4.0, n = 191 (2.9%)ACQ-5 score = 4.0-5.0, n = 29 (0.4%)ACQ-5 score = 5.0-6.0, n = 5 (0.1%)Total n = 6622No. of exacerbations∗In previous 6 weeks; collected by patient survey.0.10 (0.30)0.24 (0.43)0.32 (0.47)0.46 (0.50)0.62 (0.49)0.40 (0.55)0.18 (0.38)Self-reported adherence∗In previous 6 weeks; collected by patient survey.77.0 (35.1)75.8 (32.9)75.7 (32.2)78.2 (30.5)87.3 (25.6)76.0 (25.1)76.6 (34.0)HRU†All HRU measures collected from claims data over 4 months (2 months before and 2 months after survey completion). No. of prescriptionsAll cause5.72 (5.47)7.11 (6.80)8.56 (7.41)10.70 (9.75)11.41 (6.51)12.60 (3.44)6.64 (6.41)Asthma-specificOral prednisone0.11 (0.42)0.17 (0.51)0.25 (0.64)0.52 (0.90)0.69 (0.97)0.40 (0.55)0.16 (0.50)SABA0.37 (0.65)0.66 (0.95)0.82 (1.07)1.26 (1.29)1.28 (1.22)1.80 (0.84)0.54 (0.86)ICS0.88 (0.85)0.92 (0.95)0.98 (0.98)1.12 (1.12)1.28 (1.16)0.80 (0.84)0.91 (0.91) No. of visitsAll causeED0.05 (0.26)0.09 (0.43)0.12 (0.42)0.12 (0.36)0.21 (0.56)0.00 (0.00)0.07 (0.34)Inpatient0.02 (0.15)0.02 (0.16)0.03 (0.22)0.07 (0.34)0.10 (0.31)0.00 (0.00)0.02 (0.17)Outpatient2.05 (2.76)2.20 (3.34)2.59 (4.13)2.87 (5.07)2.93 (3.46)4.80 (2.59)2.19 (3.22)Telephone/E-mail2.76 (4.35)2.90 (4.39)3.37 (4.56)4.18 (6.38)4.90 (5.62)9.80 (9.88)2.93 (4.48)Asthma specificED0.02 (0.17)0.05 (0.33)0.08 (0.33)0.08 (0.29)0.17 (0.54)0.00 (0.00)0.04 (0.25)Inpatient0.02 (0.14)0.02 (0.15)0.03 (0.22)0.06 (0.33)0.07 (0.26)0.00 (0.00)0.02 (0.16)Outpatient0.35 (0.65)0.43 (0.76)0.53 (0.89)0.79 (1.12)1.00 (1.31)0.60 (0.55)0.41 (0.74)Telephone/E-mail0.09 (0.35)0.12 (0.38)0.15 (0.47)0.31 (0.83)0.34 (0.81)0.40 (0.55)0.11 (0.40)∗ In previous 6 weeks; collected by patient survey.† All HRU measures collected from claims data over 4 months (2 months before and 2 months after survey completion). Open table in a new tab In adjusted analyses each 1-point increase in ACQ-5 score was associated with an odds ratio of 2.14 of having an asthma exacerbation (Table II). In addition, each 1-point increase in ACQ-5 score was associated with a 21% increase in the expected number of prescriptions (all cause), a 36% and 59% increase in expected emergency department (ED) visits (all cause and asthma related, respectively), a 24% increase in expected inpatient visits, a 13% and 27% increase in expected outpatient visits, and a 62%, 47%, and 7% increase in the expected number of oral prednisone, short-acting β-agonist (SABA), and ICS prescriptions, respectively.Table IIRegression results: exacerbations and HRU (incremental effect for a 1-point change in ACQ-5 score per 4 months)Incidence rate ratioSE95% CIP valueSelf-reported exacerbations (yes/no)∗Self-reported exacerbations in previous 6 weeks.2.141†Odds ratio.0.0821.99-2.31<.001HRU‡All HRU measures collected from claims data over 4 months (2 months before and 2 months after survey completion). No. of prescriptionsAll cause1.2080.0151.18-1.24<.001Asthma specific1.2470.0171.22-1.28<.001Oral prednisone1.6170.0671.49-1.75<.001SABA1.4660.0291.41-1.52<.001ICS1.0720.0161.04-1.10<.001 No. of visits/encountersAll causeED1.3560.0831.20-1.53<.001Inpatient1.2450.1151.043-1.49.02Outpatient1.1290.0201.09-1.17<.001Telephone/E-mail encounters1.1210.0221.08-1.16<.001Asthma specificED1.5860.1251.36-1.85<.001Inpatient1.2420.1231.02-1.51.03Outpatient1.2770.0301.22-1.34<.001Telephone/E-mail encounters1.4410.0661.32-1.58<.001Controlling for round and group, age, sex, family income level, race, educational attainment, ethnicity, and smoking status.∗ Self-reported exacerbations in previous 6 weeks.† Odds ratio.‡ All HRU measures collected from claims data over 4 months (2 months before and 2 months after survey completion). Open table in a new tab Controlling for round and group, age, sex, family income level, race, educational attainment, ethnicity, and smoking status. The results of this study provide a clear indication of the deleterious effect of poor asthma control on exacerbations and HRU. Consistent with other reports, the number of exacerbations and HRU were higher when asthma was poorly controlled.2Sullivan P.W. Slejko J.F. Ghushchyan V.H. Sucher B. Globe D.R. Lin S.L. et al.The relationship between asthma, asthma control and economic outcomes in the United States.J Asthma. 2014; 51: 769-778Crossref PubMed Scopus (69) Google Scholar, 4Sullivan S.D. Rasouliyan L. Russo P.A. Kamath T. Chipps B.E. TENOR Study GroupExtent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma.Allergy. 2007; 62: 126-133Crossref PubMed Scopus (165) Google Scholar, 5Meltzer E.O. Busse W.W. Wenzel S.E. Belozeroff V. Weng H.H. Feng J. et al.Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.J Allergy Clin Immunol. 2011; 127: 167-172Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar, 6Vollmer W.M. Markson L.E. O'Connor E. Frazier E.A. Berger M. Buist A.S. Association of asthma control with health care utilization: a prospective evaluation.Am J Respir Crit Care Med. 2002; 165: 195-199Crossref PubMed Scopus (165) Google Scholar, 7Stempel D.A. McLaughin T.P. Stanford R.H. Fuhlbrigge A.L. Patterns of asthma control: a 3-year analysis of patient claims.J Allergy Clin Immunol. 2005; 115: 935-939Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 8Campbell J.D. Spackman D.E. Sullivan S.D. Health economics of asthma: assessing the value of asthma interventions.Allergy. 2008; 63: 1581-1592Crossref PubMed Scopus (22) Google Scholar Our study furthers knowledge of the relationship between asthma control and these outcomes by assessing a broad range of asthma control in a general population sample and by providing detailed quantification of how each 1-point difference in ACQ-5 score is associated with increasing exacerbations and HRU. The ACQ-5 score distribution in this study reflects a general population of patients with persistent asthma (mean, 0.99; median, 0.80). The percentage of subjects experiencing an exacerbation requiring oral corticosteroid use increased significantly as the ACQ-5 score increased, reaching 62% for those with ACQ-5 scores of between 4 and 5. HRU followed a similar pattern, with increasing ED visits, inpatient and outpatient visits, and SABA and prednisone prescriptions associated with increasing ACQ-5 scores. The findings of this study are strengthened by use of a validated measure of asthma control in a real-world setting in a general community population of patients with persistent asthma. This is in contrast to most other studies using validated measures of asthma control, which have typically been conducted in clinical trials of specialty or severe populations not generalizable to the broader asthmatic population or to studies in real-world settings that used surrogate markers of control (eg, β-agonist use or exacerbations).2Sullivan P.W. Slejko J.F. Ghushchyan V.H. Sucher B. Globe D.R. Lin S.L. et al.The relationship between asthma, asthma control and economic outcomes in the United States.J Asthma. 2014; 51: 769-778Crossref PubMed Scopus (69) Google Scholar, 4Sullivan S.D. Rasouliyan L. Russo P.A. Kamath T. Chipps B.E. TENOR Study GroupExtent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma.Allergy. 2007; 62: 126-133Crossref PubMed Scopus (165) Google Scholar, 5Meltzer E.O. Busse W.W. Wenzel S.E. Belozeroff V. Weng H.H. Feng J. et al.Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.J Allergy Clin Immunol. 2011; 127: 167-172Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar, 6Vollmer W.M. Markson L.E. O'Connor E. Frazier E.A. Berger M. Buist A.S. Association of asthma control with health care utilization: a prospective evaluation.Am J Respir Crit Care Med. 2002; 165: 195-199Crossref PubMed Scopus (165) Google Scholar, 8Campbell J.D. Spackman D.E. Sullivan S.D. Health economics of asthma: assessing the value of asthma interventions.Allergy. 2008; 63: 1581-1592Crossref PubMed Scopus (22) Google Scholar Potential limitations of the study include selection bias (subjects who were willing to participate in this study might differ from other subjects with asthma), the small proportion of subjects with ACQ scores of greater than 4.0, and recall bias associated with self-reported medication adherence and exacerbations. A more complete discussion of the limitations and ramifications of the results is provided in the Discussion section in this article's Online Repository at www.jacionline.org. Overall, the results of this study demonstrate a strong association between suboptimal asthma control and deleterious outcomes, such as more frequent exacerbations and higher HRU. The results also suggest that validated measures of control, such as the 5-question ACQ-5, can provide beneficial information for routine clinical care without undue respondent or clinical burden. The results of this analysis might also support close monitoring of asthma control in clinical practice and use of a validated control questionnaire to guide ongoing treatment decisions. Furthermore, estimates of the specific relationship between the ACQ score and exacerbations and HRU might be beneficial for population health and future applications, such as modeling the effect of disease interventions that improve asthma control through an estimation of the effect on ACQ-5 scores and subsequent HRU and exacerbations. Jon Nilsen, PhD (Amgen), provided medical writing assistance. We thank Denise Globe, PhD, for her valuable contribution to the conception and design of the study. The current study was designed to expand the understanding of the relationship between control and outcomes, including exacerbations and HRU, across a broad spectrum of patients by using a valid measure of asthma control (ACQ-5). Multiple rounds of survey administration across different allergy and flu seasons increased the range of possible ACQ scores, providing more data points to estimate this relationship. This analysis of the Observational Study of Asthma Control and Outcomes used data from a prospective survey and retrospective claims-based analysis of patients with asthma enrolled in KPCO, a group-model, closed-panel, nonprofit health maintenance organization. KPCO is the largest health care system in Colorado, providing health care services to more than 625,000 members in the Denver-Boulder metropolitan area through more than 900 physicians at 26 separate medical offices. The racial/ethnic and demographic characteristics of KPCO members are similar to those of the state as a whole. Eligible patients received surveys designed to capture information on asthma control, exacerbations, adherence, and sociodemographic characteristics during 3 rounds over the course of 1 year: between April and August 2011, between September and December 2011, and between March and June 2012. Subsequent surveys were sent to only those patients who completed the prior round. For each round, patients who did not respond after 2 attempted mailings were contacted and offered the survey by telephone. Subjects 12 years and older were identified from the KPCO database and invited to participate if they experienced persistent asthma within the previous year, as defined by clinical diagnosis and prescription drug use evidenced by 2 prescriptions of an ICS, use of omalizumab, or high use of β-agonists (>2 canisters of albuterol or equivalent within the previous 3 months). Subjects were excluded if they had a clinical diagnosis of intermittent asthma or exercise-induced asthma, but not persistent asthma, within the previous year; had a diagnosis of chronic obstructive pulmonary disease (or ≥1 prescriptions for ipratropium or tiotropium bromide and were ≥50 years of age); and lacked Kaiser prescription drug benefits or had dual insurance coverage, which would prevent accurate HRU capture in these patients. All subjects were required to have been continuously enrolled for 1 year with prescription drug benefits before the first survey date. Study variables for this analysis included asthma control, exacerbations, HRU, self-reported adherence, and sociodemographic characteristics. HRU was captured directly from the KPCO administrative databases. ACQ, adherence, and exacerbations were captured by the subject survey. Asthma control was assessed by using the ACQ-5, which is based on 5 symptom questions, resulting in a continuous score from 0 to 6, with lower scores representing better control. The authors of the ACQ demonstrated that the ACQ-5, ACQ-6, and ACQ-7 produce clinically equivalent results in aggregate, concluding that one can be used without preference over another; however, for individual treatment decisions, the ACQ-7 might provide more granular data.E1Juniper E.F. Svensson K. Mork A.C. Stahl E. Measurement properties and interpretation of three shortened versions of the asthma control questionnaire.Respir Med. 2005; 99: 553-558Abstract Full Text Full Text PDF PubMed Scopus (667) Google Scholar The ACQ-5 would likely be the most accessible to future users, requiring the fewest questions and making it more efficient for clinic practice. In addition, SABA use, the sixth item of the composite ACQ-6 score, was included as a discrete outcome in the current analyses. Given these factors, we chose to report results for the ACQ-5 rather than the ACQ-6. Survey study variables included exacerbations, controller adherence, smoking status, sex, family income level, race, educational attainment, and ethnicity. Exacerbations were ascertained by asking the following question: "In the last six weeks, have you experienced serious asthma symptoms requiring you to take oral steroid medications?" Adherence was questioned as follows: "In the last six weeks, what percent of the time did you take your daily controller medications… as prescribed (such as QVAR®, Flovent®, Advair®, Singulair®)?" HRU from the KPCO claims data was aggregated into 4-month panels (2 months before and 2 months after survey completion) with 3 rounds of surveys, resulting in three 4-month panels in 1 year. For example, total office-based visits for round 1 were calculated as the sum of all visits incurred during the 2 months preceding and 2 months after completion of the first survey. Descriptive statistics of sociodemographic variables, clinical variables, clinical outcomes, patient-reported outcomes, and HRU were assessed. Unadjusted means and SDs for all of these variables were calculated across ACQ-5 scores. For adjusted analyses, HRU measures were regressed on ACQ-5 scores (as a continuous variable) by using negative binomial models, controlling for round and group fixed effects, age, sex, family income level, race, educational attainment, ethnicity, and smoking status. Logistic regression was used for exacerbations. A common regression approach for count outcomes would be a Poisson model. However, this approach assumes that the mean and variance of the distribution are the same. The literature and our estimates show that this assumption is violated: the data exhibit overdispersion. Negative binomial regression is a robust alternative to Poison regression. It works well with count variables, particularly in the case of overdispersed count data. Preliminary examination of unadjusted results based on the survey administered over the course of 1 calendar year suggested that ACQ scores were worse in the winter than other seasons. After controlling for all covariates in regression analyses, season did not appear to be a statistically significant predictor of ACQ scores. However, based on the relatively small number of surveys completed in the winter, it is possible that a significant effect would be observed with a larger sample size of winter completers. Future research into the association between ACQ scores and season would be beneficial. However, the current research explicitly controlled for survey administration timing, thus controlling for any possible differences across seasons. Subjects in this general population sample reported high adherence levels to controller medications (77%). Although not 100%, these self-reported adherence levels might be better than averageE2Sumino K. Cabana M.D. Medication adherence in asthma patients.Curr Opin Pulm Med. 2013; 19: 49-53Crossref PubMed Scopus (62) Google Scholar; a recent systematic review reported that the mean level of adherence to ICSs was between 22% and 63%.E3Barnes C.B. Ulrik C.S. Asthma and adherence to inhaled corticosteroids: current status and future perspectives.Respir Care. 2015; 60: 455-468Crossref PubMed Scopus (205) Google Scholar It is possible that those who are likely to take the time to participate in a survey might be more interested in their asthma control and thus might be more likely to be adherent. However, it is also possible that there is some level of recall bias or purposeful overreporting in self-reported adherence. Adherence to ICSs is poor, and self-reported adherence is not always consistent with adherence determined through more objective measures, such as refill records.E4Van Steenis M. Driesenaar J. Bensing J. Van Hulten R. Souverein P. Van Dijk L. et al.Relationship between medication beliefs, self-reported and refill adherence, and symptoms in patients with asthma using inhaled corticosteroids.Patient Prefer Adherence. 2014; 8: 83-91PubMed Google Scholar A strength of this study is its generalizability to a general population of patients with persistent asthma. As expected for a general sample, very few subjects had an ACQ score of greater than 4.0. Subjects with this level of very poor control would likely be admitted to the hospital or ED and unable to participate in a community survey. As a result, conclusions regarding patients with ACQ-5 scores of greater than 4.0 must be made with caution. The potential selection bias of subjects who were willing to participate in this type of study might be a limitation of the findings. Less than half of eligible members participated. Although this is a limitation, this low response is not unexpected for an uncompensated mailed survey in a general asthmatic population. The current research controlled for survey administration timing and group, as well as explicitly controlling for sociodemographic characteristics, thereby potentially mitigating the influence of these differences. To avoid misclassifying patients with chronic obstructive pulmonary disease, we excluded patients 50 years or older who were prescribed ipratropium or tiotropium, which might have inadvertently resulted in excluding some asthmatic patients. The generalizability of the findings might also be limited by the survey response rates, as well as the geographic location of the survey. As discussed above, patients who consented to participate in the study might differ from those who declined. The extent to which these potential differences affect asthma control and outcomes is unknown but might result in underrepresentation of certain patients. The KPCO population is representative of the Colorado population, but this sample might not be generalizable to other states or regions. Measurement of exacerbations was based on self-report and is subject to associated limitations, such as recall bias. Future analyses comparing self-reported exacerbations and oral steroid use would be beneficial but was beyond the scope of this analysis. There was a small percentage of current smokers in this sample compared with other studies, which limits its generalizability. Because some subjects completed multiple surveys over time, there was a potential for serial correlation. The regressions controlled for fixed effects, including the round of the survey, but it is possible that serial correlation affected the statistical significance of the estimates. Fig E2Distribution of ACQ-5 scores for the study population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig E3Exacerbation rates by ACQ-5 scores.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table E1Sample disposition and baseline demographicsSample disposition No. of surveys completedRound 12681Round 22186Round 31799All rounds6666Baseline demographicsn = 2681 Sex (female)0.65 Mean age (y)47.9 Age group12-24 y0.1325-34 y0.1135-44 y0.1645-54 y0.2255-64 y0.2665-74 y0.0975-84 y0.03>85 y0.01 RaceWhite0.85Asian0.02African American0.04American Indian0.04Native Hawaiian0.01Multiple race0.00NA0.04 EthnicityHispanic0.13Non-Hispanic0.86NA0.01 Income (US dollars/y)<$10,0000.02$10,000-$30,0000.08$30,000-$50,0000.16$50,000-$70,0000.15$70,000-$90,0000.16>$90,0000.31NA0.04No answer0.08 EducationLess than eighth grade0.03High school but did not graduate0.05High school graduate or GED0.14Some college0.27College graduate0.25Postgraduate0.25NA0.01 Smoking historyNever smoked0.66Current smoker0.05Previous smoker0.28 Allergies∗In the previous 6 weeks.0.74 Employed0.69 Exacerbation†Exacerbation of asthma requiring the use of oral corticosteroids in the previous 6 weeks.0.19 Controller adherence∗In the previous 6 weeks.0.77Data represent proportion of patients, unless otherwise indicated. NA, Subject did not select an answer for the question; No answer, subject selected "I do not want to answer this question."∗ In the previous 6 weeks.† Exacerbation of asthma requiring the use of oral corticosteroids in the previous 6 weeks. Open table in a new tab Data represent proportion of patients, unless otherwise indicated. NA, Subject did not select an answer for the question; No answer, subject selected "I do not want to answer this question."

Describe medication utilization patterns of migraine prophylactics in commercially insured patients. Adult migraineurs (ICD-9 code 346.XX) newly initiating migraine prophylactics (no claims for 12 months before first (index) prophylactic prescription) between January 2007 and March 2013 were identified from the OptumInsight employer claims database and followed for 6 months. Prophylactics included antiepileptics (topiramate, divalproex, valproic acid), beta-blockers (propranolol, timolol), antidepressants (amitriptyline) and onabotulinumtoxinA. Continuous enrollment was required for 12 months pre-index and 6 months post-index. To increase the specificity of migraine prophylactics, patients with prior diagnoses for conditions for which their prescribed prophylactics were also indicated (i.e., epilepsy for antiepileptics, hypertension/congestive heart failure for beta-blockers, and depression for amitriptyline) were excluded. Outcomes of interest were medication adherence (medication possession ratio [MPR]), discontinuation (>30-day gap between prescriptions), and switching patterns. Time to discontinuation of initial prophylactic was described using Kaplan-Meier curves. 19,881 patients initiated prophylactic treatment with 12,136 (61%), 3,037 (15%), 4,163 (21%), and 545 (3%) patients initiating antiepileptics, beta-blockers, amitriptyline, and onabotulinumtoxinA, respectively. Mean (SD) MPR for any prophylactic was 0.49 (0.31) (0.34 (0.27)—valproic acid to 0.67 (0.22)—onabotulinumtoxinA) with a mean (SD) of 89.2 (56.7) days on treatment over 6 months. Discontinuation rates were high ranging from 74% (topiramate and onabotulinumtoxinA) to 90% (valproic acid). Switching rates ranged from 6% (topiramate) to 20% (valproic acid). Between 46% (topiramate) and 68% (timolol) patients discontinued treatment after the first prescription, and median days to discontinuation of initial treatment ranged from 30 (valproic acid, divalproex, timolol, amitriptyline) to 84 days (onabotulinumtoxinA). Adherence to migraine prophylactic medications was poor with about 50% of patients discontinuing after their first prescription and over 75% discontinuing within 6 months. The large proportion of patients discontinuing after first prescription suggests further research is needed on reasons for discontinuation and better tolerated therapies.

Background: Statins reduce the risk of coronary heart disease (CHD) in individuals with a history of CHD or risk equivalents. A 10-year CHD risk >20% is considered a risk equivalent but is frequently not detected. Statin use and low-density lipoprotein cholesterol (LDL-C) control were examined among participants with CHD or risk equivalents in the nationwide Reasons for Geographic and Racial Differences in Stroke study (n = 8812). Methods: Participants were categorized into 4 mutually exclusive groups: (1) history of CHD (n = 4025); (2) no history of CHD but with a history of stroke and/or abdominal aortic aneurysm (AAA) (n = 946); (3) no history of CHD or stroke/AAA but with diabetes mellitus (n = 3134); or (4) no history of the conditions in (1) through (3) but with 10-year Framingham CHD risk score (FRS) >20% calculated using the third Adult Treatment Panel point scoring system (n = 707). Results: Statins were used by 58.4% of those in the CHD group and 41.7%, 40.4% and 20.1% of those in the stroke/AAA, diabetes mellitus and FRS >20% groups, respectively. Among those taking statins, 65.1% had LDL-C <100 mg/dL, with no difference between the CHD, stroke/AAA, or diabetes mellitus groups. However, compared with those in the CHD group, LDL-C <100 mg/dL was less common among participants in the FRS >20% group (multivariable adjusted prevalence ratio: 0.72; 95% confidence interval: 0.62-0.85). Results were similar using the 2013 American College of Cardiology/American Heart Association cholesterol treatment guideline. Conclusions: These data suggest that many people with high CHD risk, especially those with an FRS >20%, do not receive guideline-concordant lipid-lowering therapy and do not achieve an LDL-C <100 mg/dL.

PURPOSE:The purpose of the study was to investigate secular changes in coronary heart disease (CHD) incidence and mortality among adults with and without diabetes and to determine the effect of increased lipid-lowering medication use and reductions in low-density lipoprotein cholesterol (LDL-C) levels on these changes. METHODS:We analyzed data on participants aged 45 to 64 years from the Atherosclerosis Risk in Communities Study in 1987-1996 (early period) and the Reasons for Geographic and Racial Differences in Stroke Study in 2003-2009 (late period). Hazard ratios (HRs) for the association of diabetes and period with incident CHD and CHD mortality were obtained after adjustment for sociodemographics cardiovascular risk factors, lipid-lowering medication use, and LDL-C. RESULTS:After multivariable adjustment, diabetes was associated with an increased CHD risk during the early (HR = 1.99, 95% confidence interval = 1.59-2.49) and late (HR = 2.39, 95% confidence interval = 1.69-3.35) periods. CHD incidence and mortality declined between the early and late periods for individuals with and without diabetes. Increased use of lipid-lowering medication and lower LDL-C explained 33.6% and 27.2% of the decline in CHD incidence and CHD mortality, respectively, for those with diabetes. CONCLUSIONS:Although rates have declined, diabetes remains associated with an increased risk of CHD incidence and mortality, highlighting the need for continuing diabetes prevention and cardiovascular risk factor management.