Evolution of economic burden of heart failure by ejection fraction in newly diagnosed patients in Spain.

OBJECTIVE: To describe healthcare resource utilization (HCRU) and costs, in patients with newly diagnosed heart failure (HF) according to ejection fraction (EF) in Spain. METHODS: Retrospective cohort study that analyzed anonymized, integrated and computerised medical records in Spain. Patients with ≥ 1 new HF diagnosis between January 2013 and September 2019 were included and followed-up during a 4-year period. Rates per 100 person-years of HCRU and costs were estimated. RESULTS: Nineteen thousand nine hundred sixty-one patients were included, of whom 43.5%, 26.3%, 5.1% and 25.1% had HF with reduced, preserved, mildly reduced and unknown EF, respectively. From year 1 to 4, HF rates of outpatient visits decreased from 1149.5 (95% CI 1140.8-1159.3) to 765.5 (95% CI 745.9-784.5) and hospitalizations from 61.7 (95% CI 60.9-62.7) to 15.7(14.7-16.7) per 100 person-years. The majority of HF-related healthcare resource costs per patient were due to hospitalizations (year 1-4: 63.3-38.2%), followed by indirect costs (year 1-4: 12.2-29.0%), pharmacy (year 1-4: 11.9-19.9%), and outpatient care (year 1-4: 12.6-12.9%). Mean (SD) per patient HF-related costs decreased from 2509.6 (3518.5) to 1234.6 (1534.1) Euros (50% cost reduction). At baseline, 70.1% were taking beta-blockers, 56.3% renin-angiotensin system inhibitors, 11.8% mineralocorticoid receptor antagonists and 8.9% SGLT2 inhibitors. At 12 months, these numbers were 72.3%, 65.4%, 18.9% and 9.8%, respectively. CONCLUSIONS: Although the economic burden of HF decreased over time since diagnosis, it is still substantial. This reduction could be partially related to a survival bias (sick patients died early), but also to a better HF management. Despite that, there is still much room for improvement.

Comparing the long-term outcomes in chronic coronary syndrome patients with prior ST-segment and non-ST-segment elevation myocardial infarction: findings from the TIGRIS registry.

OBJECTIVES: Compared with ST-segment elevation myocardial infarction (STEMI) patients, non-STEMI (NSTEMI) patients have more comorbidities and extensive coronary artery disease. Contemporary comparative data on the long-term prognosis of stable post-myocardial infarction subtypes are needed. DESIGN: Long-Term rIsk, clinical manaGement and healthcare Resource utilisation of stable coronary artery dISease (TIGRIS) was a multinational, observational and longitudinal cohort study. SETTING: Patients were enrolled from 350 centres, with >95% coming from cardiology practices across 24 countries, from 19 June 2013 to 31 March 2017. PARTICIPANTS: This study enrolled 8277 stable patients 1-3 years after myocardial infarction with ≥1 additional risk factor. OUTCOME MEASURES: Over a 2 year follow-up, cardiovascular events and deaths and self-reported health using the EuroQol 5-dimension questionnaire score were recorded. Relative risk of clinical events and health resource utilisation in STEMI and NSTEMI patients were compared using multivariable Poisson regression models, adjusting for prognostically relevant patient factors. RESULTS: Of 7752 patients with known myocardial infarction type, 46% had NSTEMI; NSTEMI patients were older with more comorbidities than STEMI patients. NSTEMI patients had significantly poorer self-reported health and lower prevalence of dual antiplatelet therapy at hospital discharge and at enrolment 1-3 years later. NSTEMI patients had a higher incidence of combined myocardial infarction, stroke and cardiovascular death (5.6% vs 3.9%, p<0.001) and higher all-cause mortality (4.2% vs 2.6%, p<0.001) compared with STEMI patients. Risks were attenuated after adjusting for other patient characteristics. Health resource utilisation was higher in NSTEMI patients, although STEMI patients had more cardiologist visits. CONCLUSIONS: Post-NSTEMI chronic coronary syndrome patients had a less favourable risk factor profile, poorer self-reported health and more adverse cardiovascular events during long-term follow-up than individuals post STEMI. Efforts are needed to recognise the risks of stable patients after NSTEMI and optimise secondary prevention and care. TRIAL REGISTRATION NUMBER: NCT01866904.

Evaluating clinical outcomes and prognosis in patients with cirrhosis and portal hypertension: a retrospective observational cohort study.

OBJECTIVE: Cirrhosis describes the end-stage of chronic liver disease. Irreversible changes in the liver cause portal hypertension, which can progress to serious complications and death. Only a few studies with small sample sizes have investigated the prognosis of cirrhosis with portal hypertension. We used electronic healthcare records to examine liver-related outcomes in patients with diagnosed/suspected portal hypertension. DESIGN: This retrospective observational cohort study used secondary health data between 1 January 2017 and 3 December 2020 from the TriNetX Network, a federated electronic healthcare records platform. Three patient groups with cirrhosis and diagnosed/suspected portal hypertension were identified ('most severe', 'moderate severity' and 'least severe'). Outcomes studied individually and as a composite were variceal haemorrhage, hepatic encephalopathy, complications of ascites and recorded mortality up to 24 months. RESULTS: There were 13 444, 23 299, and 23 836 patients in the most severe, moderate severity and least severe groups, respectively. Mean age was similar across groups; most participants were white. The most common individual outcomes at 24 months were variceal haemorrhage in the most severe group, recorded mortality and hepatic encephalopathy in the moderate severity group, and recorded mortality in the least severe group. Recorded mortality rate was similar across groups. For the composite outcome, cumulative incidence was 59% in the most severe group at 6 months. Alcohol-associated liver disease and metabolic-associated steatohepatitis were significantly associated with the composite outcome across groups. CONCLUSION: Our analysis of a large dataset from electronic healthcare records illustrates the poor prognosis of patients with diagnosed/suspected portal hypertension.

Long-term outcomes among stable post-acute myocardial infarction patients living in rural versus urban areas: insights from the prospective, observational TIGRIS registry.

BACKGROUND: Insights on the differences in clinical outcomes, quality of life (QoL) and health resource utilisation (HRU) with different levels of care available to post-acute myocardial infarction (AMI) populations in rural and urban settings are limited. METHODS: The long-Term rIsk, clinical manaGement, and healthcare Resource utilisation of stable coronary artery dISease (TIGRIS), a prospective, observational registry, enrolled 8452 patients aged ≥50 years 1-3 years post-AMI from June 2013 to November 2014 from 24 countries in Asia Pacific/Australia, Europe, North America and South America. Differences in QoL (measured using the EuroQol Research Foundation instrument) and HRU between patients in rural and urban settings were evaluated in this post hoc analysis. The incidence of clinical endpoints (cardiovascular (CV) death, AMI, unstable angina with urgent revascularisation and stroke; bleeding; and all-cause mortality) was analysed. Data were collected at baseline and every 6 months for 24 months. RESULTS: There were fewer hospitalisations and visits to general practitioners (GPs) and cardiologists in the rural versus urban populations (adjusted event rate ratio (ERR)=0.90 (95% CI, 0.82 to 1.00, p=0.04); ERR=0.84 (95% CI, 0.78 to 0.92, p<0.001); ERR=0.86 (95% CI, 0.81 to 0.92, p<0.001), respectively). No statistically significant differences were observed between rural and urban populations in all-cause death, AMI, unstable angina with urgent revascularisation, CV death, stroke, major bleeding events and health-related QoL. The adjusted incidence rate ratio was 0.92 (95% CI, 0.74 to 1.15) for the composite of CV death, AMI and stroke. CONCLUSIONS: Living in rural areas was associated with fewer GP/cardiologist visits and hospitalisations; no significant differences in clinical outcomes and QoL were observed. TRIAL REGISTRATION NUMBER: NCT01866904.

Testing the "RCT augmentation" methodology: A trial simulation study to guide the broadening of trials eligibility criteria and inform on effectiveness.

Background: Exclusion criteria that are treatment effect modifiers (TEM) decrease RCTs results generalisability and the potentials of effectiveness estimation. In "augmented RCTs", a small proportion of otherwise-excluded patients are included to allow for effectiveness estimation. In Hodgkin Lymphoma (HL) RCTs, older age and comorbidity are common exclusion criteria, while also TEM. We simulated HL RCTs augmented with age or comorbidity, and explored in each scenario the impact of augmentation on effectiveness estimation accuracy. Methods: Simulated data with a population of HL individuals initiating drug A or B was generated. There were drug-age and drug-comorbidity interactions in the simulated data, with a greater magnitude of the former compared to the latter. Multiple augmented RCTs were simulated by randomly selecting patients with increasing proportions of older, or comorbid patients. Treatment effect size was expressed using the between-group Restricted Mean Survival Time (RMST) difference at 3 years. For each augmentation proportion, a model estimating the "real-world" treatment effect (effectiveness) was fitted and the estimation error measured (Root Mean Square Error, RMSE). Results: In simulated RCTs including none (0%), or the real-world proportion (30%) of older patients, the interquartile range of RMST difference was 0.4-0.5 years and 0.2-0.3 years, respectively, and RMSE were 0.198 years (highest possible error) and 0.056 years (lowest), respectively. Augmenting RCTs with 5% older patients decreased estimation error substantially (RMSE = 0.076 years). Augmentation with comorbid patients proved less useful for effectiveness estimation. Conclusion: In augmented RCTs aiming to inform the effectiveness of drugs, augmentation should concern in priority those exclusion criteria of suspected important TEM magnitude, so as to minimie the proportion of augmentation necessary for good effectiveness estimations.

Burden of Illness beyond Mortality and Heart Failure Hospitalizations in Patients Newly Diagnosed with Heart Failure in Spain According to Ejection Fraction.

OBJECTIVE: The objective of this study was to describe the rates of adverse clinical outcomes, including all-cause mortality, heart failure (HF) hospitalization, myocardial infarction, and stroke, in patients newly diagnosed with HF to provide a comprehensive picture of HF burden. METHODS: This was a retrospective and observational study, using the BIG-PAC database in Spain. Adults, newly diagnosed with HF between January 2013 and September 2019 with ≥1 HF-free year of enrolment prior to HF diagnosis, were included. RESULTS: A total of 19,961 patients were newly diagnosed with HF (43.5% with reduced ejection fraction (EF), 26.3% with preserved EF, 5.1% with mildly reduced EF, and 25.1% with unknown EF). The mean age was 69.7 ± 19.0 years; 53.8% were men; and 41.0% and 41.5% of patients were in the New York Heart Association functional classes II and III, respectively. The baseline HF treatments included beta-blockers (70.1%), renin-angiotensin system inhibitors (56.3%), mineralocorticoid receptor antagonists (11.8%), and SGLT2 inhibitors (8.9%). The post-index incidence rates of all-cause mortality, HF hospitalization, and both combined were 102.2 (95% CI 99.9-104.5), 123.1 (95% CI 120.5-125.7), and 182 (95% CI 178.9-185.1) per 1000 person-years, respectively. The rates of myocardial infarction and stroke were lower (26.2 [95% CI 25.1-27.4] and 19.8 [95% CI 18.8-20.8] per 1000 person-years, respectively). CONCLUSIONS: In Spain, patients newly diagnosed with HF have a high risk of clinical outcomes. Specifically, the rates of all-cause mortality and HF hospitalization are high and substantially greater than the rates of myocardial infarction and stroke. Given the burden of adverse outcomes, these should be considered targets in the comprehensive management of HF. There is much room for improving the proportion of patients receiving disease-modifying therapies.

Post-Authorization Safety Studies of Acute Liver Injury and Severe Complications of Urinary Tract Infection in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting.

INTRODUCTION: At the time of dapagliflozin's approval in Europe (2012) to treat patients with type 2 diabetes mellitus, concerns regarding acute liver injury and severe complications of urinary tract infection (sUTI) led to two post-authorization safety (PAS) studies of these outcomes to monitor the safety of dapagliflozin in real-world use. OBJECTIVE: To investigate the incidence of hospitalization for acute liver injury (hALI) or sUTI (pyelonephritis or urosepsis) among patients initiating dapagliflozin compared with other glucose-lowering drugs (GLDs). METHODS: These two noninterventional cohort studies identified initiators of dapagliflozin and comparator GLDs in November 2012-February 2019 using data from three longitudinal, population-based data sources: Clinical Practice Research Datalink (UK), the HealthCore Integrated Research Database (USA), and the Medicare database (USA). Outcomes (hALI and sUTI) were identified with electronic algorithms. Incidence rates were estimated by exposure group. Incidence rate ratios (IRRs) were calculated comparing dapagliflozin to comparator GLDs, using propensity score trimming and stratification to address confounding. The sUTI analyses were conducted separately by sex. RESULTS: In all data sources, hALI and sUTI incidence rates were generally lower in dapagliflozin initiators than comparator GLD initiators. The adjusted IRR (95% confidence interval) pooled across data sources for hALI was 0.85 (0.59-1.24) and for sUTI was 0.76 (0.60-0.96) in females and 0.74 (0.56-1.00) in males. Findings from sensitivity analyses were largely consistent with the primary analyses. CONCLUSIONS: These real-world studies do not suggest increased risks of hALI or sUTI, and they suggest a potential decreased risk of sUTI with dapagliflozin exposure compared with other GLDs.

Post-Authorization Safety Study of Hospitalization for Acute Kidney Injury in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting.

INTRODUCTION: Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor approved to treat type 2 diabetes mellitus (T2DM), among other conditions. When dapagliflozin was approved in Europe for treating T2DM (2012), potential safety concerns regarding its effect on kidney function resulted in this post-authorization safety study to assess hospitalization for acute kidney injury (hAKI) among dapagliflozin initiators in a real-world setting. OBJECTIVE: The aim of this study was to evaluate the incidence of hAKI in adults with T2DM initiating dapagliflozin compared with other glucose-lowering drugs (GLDs). METHODS: This noninterventional cohort study identified new users of dapagliflozin and comparator GLDs from November 2012 to February 2019 from three longitudinal, population-based data sources: Clinical Practice Research Datalink (CPRD; United Kingdom), the HealthCore Integrated Research Database (HIRD; United States [US]), and Medicare (US). Electronic algorithms identified occurrences of hAKI, from which a sample underwent validation. Incidence rates for hAKI were calculated, and incidence rate ratios (IRRs) compared hAKI in dapagliflozin with comparator GLDs. Propensity score trimming and stratification were conducted for confounding adjustment. RESULTS: In all data sources, dapagliflozin initiators had a lower hAKI incidence rate than comparator GLD initiators (adjusted IRRs: CPRD, 0.44 [95% confidence interval (CI), 0.22-0.86]; HIRD, 0.76 [95% CI, 0.62-0.93]; Medicare, 0.69 [95% CI, 0.59-0.79]). The adjusted IRR pooled across the data sources was 0.70 (95% CI, 0.62-0.78). Results from sensitivity and stratified analyses were consistent with the primary analysis. CONCLUSIONS: This study, with > 34,000 person-years of real-world dapagliflozin exposure, suggests a decreased risk of hAKI in patients with T2DM exposed to dapagliflozin, aligning with results from dapagliflozin clinical trials. STUDY REGISTRATION: European Union Post-Authorisation Studies Register, EUPAS 11684; ClinicalTrials.gov, NCT02695082.

Healthcare resource utilization and costs among patients with heart failure with preserved, mildly reduced, and reduced ejection fraction in Spain.

AIMS: To describe healthcare resource utilization (HCRU) of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain.  METHODS: Adults with ≥ 1 HF diagnosis and ≥ 1 year of continuous enrolment before the corresponding index date (1/January/2016) were identified through the BIG-PAC database. Rate per 100 person-years of all-cause and HF-related HCRU during the year after the index date were estimated using bootstrapping with replacement. RESULTS: Twenty-one thousand two hundred ninety-seven patients were included, of whom 48.5% had HFrEF, 38.6% HFpEF and 4.2% HFmrEF, with the rest being of unknown EF. Mean age was 78.8 ± 11.8 years, 53.0% were men and 83.0% were in NYHA functional class II/III. At index, 67.3% of patients were taking renin angiotensin system inhibitors, 61.2% beta blockers, 23.4% aldosterone antagonists and 5.2% SGLT2 inhibitors. Rates of HF-related outpatient visits and hospitalization were 968.8 and 51.6 per 100 person-years, respectively. Overall, 31.23% of patients were hospitalized, mainly because of HF (87.88% of total hospitalizations); HF hospitalization length 21.06 ± 17.49 days (median 16; 25th, 75th percentile 9-27). HF hospitalizations were the main cost component: inpatient 73.64%, pharmacy 9.67%, outpatient 9.43%, and indirect cost 7.25%. Rates of all-cause and HF-related HCRU and healthcare cost were substantial across all HF subgroups, being higher among HFrEF compared to HFmrEF and HFpEF patients. CONCLUSIONS: HCRU and cost associated with HF are high in Spain, HF hospitalizations being the main determinant. Medication cost represented only a small proportion of total costs, suggesting that an optimization of HF therapy may reduce HF burden.

Prevalence, Characteristics, Management and Outcomes of Patients with Heart Failure with Preserved, Mildly Reduced, and Reduced Ejection Fraction in Spain.

Objective: To estimate the prevalence, incidence, and describe the characteristics and management of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain. Methods: Adults with ≥1 inpatient or outpatient HF diagnosis between 1 January 2013 and 30 September 2019 were identified through the BIG-PAC database. Annual incidence and prevalence by EF phenotype were estimated. Characteristics by EF phenotype were described in the 2016 and 2019 HF prevalent cohorts and outcomes in the 2016 HF prevalent cohort. Results: Overall, HF incidence and prevalence were 0.32/100 person-years and 2.34%, respectively, but increased every year. In 2019, 49.3% had HFrEF, 38.1% had HFpEF, and 4.3% had HFmrEF (in 8.3%, EF was not available). Compared with HFrEF, patients with HFpEF were largely female, older, and had more atrial fibrillation but less atherosclerotic cardiovascular disease. Among patients with HFrEF, 76.3% were taking renin-angiotensin system inhibitors, 69.5% beta-blockers, 36.8% aldosterone antagonists, 12.5% sacubitril/valsartan and 6.7% SGLT2 inhibitors. Patients with HFpEF and HFmrEF took fewer HF drugs compared to HFrEF. Overall, the event rates of HF hospitalization were 231.6/1000 person-years, which is more common in HFrEF patients. No clinically relevant differences were found in patients with HFpEF, regardless EF (50- < 60% vs. ≥60%). Conclusions: >2% of patients have HF, of which around 50% have HFrEF and 40% have HFpEF. The prevalence of HF is increasing over time. Clinical characteristics by EF phenotype are consistent with previous studies. The risk of outcomes, particularly HF hospitalization, remains high, likely related to insufficient HF treatment.

The absolute risk of incident type 2 diabetes following exposure to systemic corticosteroids in selected steroid-related and phenotypic groups.

AIMS: Exposure to corticosteroids is known to increase the risk of developing type 2 diabetes. We estimated the risk of incident type 2 diabetes in selected patient groups exposed to systemic corticosteroids. MATERIALS AND METHODS: In a retrospective, observational cohort study, using real-world data from UK primary care, patients were selected who had at least one episode of exposure to oral or intravenous corticosteroids for any indication. Corticosteroid-exposed patients were matched with non-exposed patients. Relative dosage was estimated as a weight-based, prednisolone-equivalent dose. Crude rates of progression to type 2 diabetes were determined for patient groups defined by relevant steroid-related and phenotypic characteristics present at corticosteroid exposure. RESULTS: Overall, rates of incidence of type 2 diabetes were 12.5 and 6.7 events per thousand person-years' (pkpy) exposure, respectively, in those who received at least one dose of corticosteroids versus those never exposed. This represented a rate ratio of 1.85 (95% CI 1.74-1.97). The incidence of type 2 diabetes was found to be associated with several of the selected characteristics, both individually and multi-dimensionally. The highest rate of incident type 2 diabetes was observed in very severely obese men aged 46-55 years having had the longest corticosteroid exposure and highest corticosteroid dose (190 incident events pkpy exposure). CONCLUSIONS: Corticosteroid exposure increased the risk of incident type 2 diabetes, and there was evidence of both a dose-response and a duration response. The impact of corticosteroid exposure upon the rate of incident type 2 diabetes appeared, however, to involve a complex, multi-dimensional interaction between the selected characteristics, some of which might be impacted by reverse causality.

Assessment of The High risk and unmEt Need in patients with CAD and type 2 diabetes (ATHENA): US healthcare resource use, cost, and burden of illness in a commercially insured population.

AIMS: THEMIS (NCT01991795) demonstrated cardioprotective benefits of ticagrelor plus acetylsalicylic acid (ASA) compared with placebo plus ASA in patients with type 2 diabetes (T2D), stable coronary artery disease (CAD) and no history of myocardial infarction (MI) or stroke. To complement these findings, we assessed clinical outcomes and healthcare costs in commercially insured US patients similar to those in THEMIS. METHODS: This retrospective, observational study used data from Optum. The T2D-CAD cohort (n = 154,369) included patients (≥50 years old) either with high cardiovascular risk or taking a P2Y12 inhibitor. The THEMIS-like cohort (n = 126,938) comprised patients (≥50 years old) at high cardiovascular risk; the THEMIS-PCI-like cohort comprised a subset of these patients with prior percutaneous coronary intervention (PCI) (n = 18,394). RESULTS: Mean follow-up was 2.4-2.5 years. Incidence rates of the composite outcome (death, MI, and stroke) were 6.56 (95% CI 6.50-6.63), 6.21 (6.14-6.28), and 5.57 (5.39-5.74) per 100 person-years, and annualized healthcare costs per patient were US$15,848, US$16,044, and US$20,934 for the T2D-CAD, THEMIS-like, and THEMIS-PCI-like cohorts, respectively. CONCLUSIONS: Commercially insured patients similar to those in THEMIS had high cardiovascular event rates and healthcare costs, highlighting a need for improved preventive strategies.

Assessment of the high risk and unmet need in patients with CAD and type 2 diabetes (ATHENA): US healthcare resource utilization, cost and burden of illness in the Diabetes Collaborative Registry.

BACKGROUND: THEMIS (NCT01991795) showed that in patients with type 2 diabetes (T2D) and stable coronary artery disease (CAD) but with no prior myocardial infarction (MI) or stroke, ticagrelor plus acetylsalicylic acid (ASA) decreased the incidence of ischaemic cardiovascular events compared with placebo plus ASA. To complement these findings, we assessed disease burden and healthcare resource utilization (HRU) in US patients with CAD and T2D, but without a prior MI or stroke. METHODS: This observational study used 2013-2014 data from the Diabetes Collaborative Registry linked to Medicare administrative claims. Two cohorts of patients with T2D were studied: patients at high cardiovascular risk (THEMIS-like cohort; N = 56 040) and patients at high cardiovascular risk or taking P2Y12 inhibitors (CAD-T2D cohort; N = 69 790). Outcomes included the composite of all-cause death, MI and stroke; the individual events from the composite endpoint; HRU; and costs. RESULTS: Median age was 73.0 years, and median follow-up was 1.3 years in both cohorts. Event rates of the composite outcome were 16.34 (95% confidence interval: 16.31-16.37) and 17.64 (17.61-17.67) per 100 person-years for the THEMIS-like and CAD-T2D cohorts, respectively. The incidence rate of bleeding events was 0.13 events per 100 person-years in both cohorts. Healthcare costs per patient-year were USD 8741 and USD 9150 in the THEMIS-like and CAD-T2D cohorts, respectively. CONCLUSIONS: Patients in the THEMIS-like cohort and the broader CAD-T2D population had similarly substantial cardiovascular event rates and healthcare costs, indicating that patients with CAD and T2D similar to the THEMIS population are at an increased cardiovascular risk.

Differences between patients with type 1 diabetes with optimal and suboptimal glycaemic control: A real-world study of more than 30 000 patients in a US electronic health record database.

AIMS: To use electronic health record data from real-world clinical practice to assess demographics, clinical characteristics and disease burden of adults with type 1 diabetes (T1D) in the United States. MATERIALS AND METHODS: Retrospective observational study of adults with T1D for ≥24 months at their first visit with a T1D diagnosis code ("index date") between July 2014 and June 2016 in the Optum Humedica database. Demographic characteristics, acute complications (severe hypoglycaemia [SH], diabetic ketoacidosis [DKA]), microvascular complications, cardiovascular (CV) events and health care resource utilization during the 12 months before the index date ("baseline period") were compared between patients with optimal versus suboptimal glycaemic control (glycated haemoglobin [HbA1c] <7.0% vs. ≥7.0% [53 mmol/mol]) at the closest measurement to the index date. RESULTS: Of 31 430 adults with T1D, 79.9% had suboptimal glycaemic control (mean HbA1c 8.8% [73 mmol/mol]). These patients were more likely to be younger, African American, uninsured or on Medicaid, obese, smokers, have uncontrolled hypertension and have depression. Despite worse glycaemic control and increased CV risk factors of uncontrolled hypertension, obesity and smoking, rates of coronary heart disease and stroke were not higher in these patients. Patients with suboptimal glycaemic control also experienced more diabetes complications (including SH, DKA and microvascular disease) and utilized more emergency care, with more emergency department visits and inpatient stays. CONCLUSION: This real-world study of >30 000 adults with T1D showed that individuals with suboptimal versus optimal glycaemic control differed significantly in terms of health care coverage, comorbidities, diabetes-related complications, health care utilization and CV risk factors. However, suboptimal control was not associated with increased risk of CV outcomes.

Incidences of Severe Hypoglycemia and Diabetic Ketoacidosis and Prevalence of Microvascular Complications Stratified by Age and Glycemic Control in U.S. Adult Patients With Type 1 Diabetes: A Real-World Study.

OBJECTIVE: To assess the burden of disease for adults with type 1 diabetes in a U.S. electronic health record database by evaluating acute and microvascular complications stratified by age and glycemic control. RESEARCH DESIGN AND METHODS: This is a retrospective observational study of adults with type 1 diabetes (1 July 2014-30 June 2016) classified using a validated algorithm, with disease duration ≥24 months and, during a 12-month baseline period, not pregnant and having one or more insulin prescriptions and one or more HbA1c measurements. Demographic characteristics, acute complications (severe hypoglycemia [SH], diabetic ketoacidosis [DKA]), and microvascular complications (neuropathy, nephropathy, retinopathy) were stratified by age (18-25, 26-49, 50-64, ≥65 years) and glycemic control (HbA1c <7%, 7% to <9%, ≥9%). RESULTS: Of 31,430 patients, ∼20% had HbA1c <7%. Older patients had lower HbA1c values than younger patients (P < 0.001). Patients with poor glycemic control had the highest annual incidence of SH (4.2%, 4.0%, and 8.3%) and DKA (1.3%, 2.8%, and 15.8%) for HbA1c <7%, 7% to <9%, and ≥9% cohorts, respectively (both P < 0.001), and a higher prevalence of neuropathy and nephropathy (both P < 0.001). CONCLUSIONS: For adults with type 1 diabetes, glycemic control appears worse than previously estimated. Rates of all complications increased with increasing HbA1c. Compared with HbA1c <7%, HbA1c ≥9% was associated with twofold and 12-fold higher incidences of SH and DKA, respectively. Younger adults had more pronounced higher risks of SH and DKA associated with poor glycemic control than older adults.

Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes.

OBJECTIVE: The goal of this study was to evaluate the association between the timing of treatment intensification and subsequent glycemic control among patients with type 2 diabetes in whom monotherapy fails. RESEARCH DESIGN AND METHODS: This retrospective analysis of the U.K. Clinical Practice Research Datalink database focused on patients with type 2 diabetes and one or more HbA1c measurements ≥7% (≥53 mmol/mol) after ≥3 months of metformin or sulfonylurea monotherapy (first measurement meeting these criteria was taken as the study index date). Baseline (6 months before the index date) characteristics were stratified by time from the index date to intensification (early: <12 months; intermediate: 12 to <24 months; late: 24 to <36 months). Intensification was defined as initiating after the index date one or more noninsulin antidiabetes medication in addition to metformin or a sulfonylurea. Association between time to intensification and subsequent glycemic control (first HbA1c <7% [<53 mmol/mol] after intensification) was evaluated using Kaplan-Meier analyses and Cox proportional hazard models that accounted for baseline differences. RESULTS: Of the 93,515 patients who met the study criteria (mean age 60 years; ∼59% male; 80% taking metformin), 23,761 (25%) intensified <12 months after the index date; 11,908 (13%) intensified after 12 to <24 months; and 7,146 (8%) intensified after 24 to <36 months. Patients who intensified treatment ≥36 months after the index date (n = 9,638 [10%]) and those with no evidence of treatment intensification during the observable follow-up period (n = 41,062 [44%]) were not included in further analyses. The median times from intensification to control were 20.0, 24.1, and 25.7 months, respectively, for the early, intermediate, and late intensification cohorts. After adjustment for baseline differences, the likelihood of attaining glycemic control was 22% and 28% lower for patients in the intermediate and late intensification groups, respectively, compared with those intensifying early (P < 0.0001). CONCLUSIONS: Earlier treatment intensification is associated with shorter time to subsequent glycemic control, independent of whether patients initiate first-line treatment with metformin or a sulfonylurea.

Clinical and economic outcomes among elderly myocardial infarction survivors in the United States.

OBJECTIVES: Longitudinal data are limited regarding outcomes and costs beyond 1 year after acute myocardial infarction (MI) among elderly (≥65 years old) US patients. This study examined long-term outcomes and healthcare costs among elderly MI survivors. METHODS: Retrospective analysis of 2002-2009 Medicare healthcare claims (5% random sample). Patients were ≥65 years old and survived ≥1 year without recurrent MI after MI hospitalization. Mortality, incidence of hospitalizations for stroke, major bleeding, MI, a composite endpoint (death, MI, or stroke), and nonpharmacy healthcare costs were determined. RESULTS: Eligible patients included 16 244 STEMI, 34 576 NSTEMI, and 3109 unspecified MI. NSTEMI and unspecified MI patients had significantly higher prevalence of comorbidities than STEMI patients, except for hypertension and dyslipidemia. MI incidence declined 36% over the follow-up (3.82/100 person-years [PY] to 2.45/100 PY). Mortality, stroke, and bleeding decreased until the third year of follow-up and then increased. NSTEMI and unspecified MI patients had a significantly higher incidence of death, MI, the composite, and bleeding than STEMI patients throughout follow-up. All-cause inpatient costs during follow-up were 2.6- and 1.9-fold higher than baseline for STEMI and NSTEMI, respectively; cardiovascular-related inpatient costs were 3.5- and 2.2-fold higher, respectively. CONCLUSIONS: Risks of mortality and cardiovascular events remain high in a Medicare population surviving >1 year after a MI. Continuing healthcare costs are doubled over pre-MI levels up to 5 years after an MI. Secondary prevention measures beyond the acute post-MI period may be indicated to reduce risk and cost in this chronic disease phase.

Long-term cardiovascular risk and costs for myocardial infarction survivors in a US commercially insured population.

OBJECTIVE: To quantify clinical and cost long-term outcomes in cardiovascular stable post-myocardial-infarction patients. RESEARCH DESIGN AND METHODS: Subjects with a history of myocardial infarction (MI) who were 50-64 years old and MI- and stroke-free for ≥12 months (index date) were identified in a large US claims database. Individuals were followed for up to 5 years (mean: 2.0 years) after their index date. MAIN OUTCOME MEASURES: Rates of MI, stroke, all-cause death, and a composite of these were analyzed via Cox regression models, adjusted for covariates. Results are reported for the overall population and the subgroups of those with type 2 diabetes, additional prior MI, and non-end-stage renal disease. As a secondary endpoint healthcare costs were evaluated at baseline and during each year of follow-up. Results Over the follow-up period, which averaged 2 years, 7.6% of all 13,492 subjects (10.5% vs. 5.4% with and without the selected risk factors, respectively) experienced at least one of the outcome events. The cumulative incidence rates over the entire follow-up period for the primary composite outcome were 20.8% and 12.2% for those with and without the selected atherothrombotic risk factors, respectively. The cardiovascular-related per-person-per-year healthcare costs during follow-up were higher in those with ≥1 additional risk factor compared to those without: $15,247 versus $7521. Costs were elevated over baseline costs throughout follow-up. LIMITATIONS: Administrative claims data lack clinical detail. Generalizability of results is limited to the US commercially insured population of a similar age to that included in this study. CONCLUSIONS: High risk MI survivors who have been event free for ≥1 year remained at substantial risk of CV events and had increased healthcare costs for up to 5 years post-MI. These long-term risks have not been previously demonstrated in a working-age US population and suggest an unmet need for continuing secondary prevention long-term post-MI.

Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction.

AIMS: To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. METHODS AND RESULTS: We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002-11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04-1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21-1.96)]. CONCLUSION: The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.