Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: "INSIST" study.

BACKGROUND: People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France. METHODS: We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs. RESULTS: Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47-7.15] versus 1.38 [1.24-1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7-159.0] versus 126.4 [117.2-136.4]; stroke recurrence: 86.7 [66.4-113.4] versus 66.5 [59.2-74.6]; mortality 291.5 [259.1-327.9] versus 144.1 [134.3-154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66-2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378). CONCLUSIONS: The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.

External control arms for rare diseases: building a body of supporting evidence.

Comparator arms in randomized clinical trials may be impractical and/or unethical to assemble in rare diseases. In the absence of comparator arms, evidence generated from external control studies has been used to support successful regulatory submissions and health technology assessments (HTA). However, conducting robust and rigorous external control arm studies is challenging and despite all efforts, residual biases may remain. As a result, regulatory and HTA agencies may request additional external control analyses so that decisions may be made based upon a body of supporting evidence.This paper introduces external control studies and provides an overview of the key methodological issues to be considered in the design of these studies. A series of case studies are presented in which evidence derived from one or more external controls was submitted to regulatory and HTA agencies to provide support for the consistency of findings.

Fractures in untreated patients with osteoporosis in Germany: an InGef healthcare insurance database analysis.

Osteoporosis is a skeletal disease that may result in low-trauma fracture if untreated. Among men and women ≥ 70 years untreated for osteoporosis, 30% (43,514) sustained at least one post-index fracture. Care for patients with osteoporosis diagnosis directly contributed to a cost burden of €786 million. INTRODUCTION: Osteoporosis is a skeletal disease that manifests as bone mineral density loss and low-trauma fractures. This database analysis describes the characteristics of untreated osteoporosis patients, and their rate of fractures, health resource utilization, and cost burden. METHODS: From the InGef database (2011-2016), eligible patients (≥ 70 years) untreated for osteoporosis were identified via a recorded diagnosis of osteoporosis (ICD-10 codes M80/M81) or an initial fragility fracture (index point). All patients were followed up for fractures post index. Direct costs included inpatient, outpatient, pharmacy, and ancillary care costs. RESULTS: A total of 144,752 patients (mean age 79 years; 73% female, median follow-up of 3.2 years) met the eligibility criteria; 23% had a history of fractures. Forty-eight percent of patients had cardiac diseases, 32% diabetes, and 27% cerebrovascular disease. Thirty percent (43,514) of patients had at least one post-index fracture; two or more post-index fractures were experienced in 7% (10,262) of patients. Median time from index date to first fracture was 145.5 days. Bisphosphonates were the most prescribed osteoporosis treatment following a first fracture post-index (n = 4102, 9.2%). There was a total of 107,055 patients (74.0%) who had at least one all-cause hospital stay. The total number of fracture-related admissions was 63,595 and that of outpatient visits was 323,460. A total of 34,764 (24%) patients died during follow-up. Costs for fracture-related care for patients directly contributed to a cost burden of €786 million. CONCLUSIONS: Osteoporosis patients and patients who sustain a fragility fracture remain undertreated for osteoporosis, increasing their risk of future fractures. Diagnosing and treating this group of patients should remain a priority to alleviate the clinical and economic burden of osteoporosis-related fractures.

International cohort study on the effectiveness of dronedarone and other antiarrhythmic drugs for atrial fibrillation in real-world practice (EFFECT-AF).

AIMS: To evaluate the effectiveness and safety of dronedarone compared with other commonly used antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrences. METHODS AND RESULTS: An international observational cohort study in Germany, Spain, Italy, and the USA enrolling patients with AF receiving AAD therapy. Patients with New York Heart Association (NYHA) Class IV heart failure were excluded. Participants were followed for up to 18 months, regardless of discontinuation or subsequent AAD switches. Atrial fibrillation recurrence was captured by hospitalization, emergency room visit, or electrocardiogram-based documentation of AF. Confounding bias was controlled for in the analysis of AF recurrence using multivariate models of 19 variables for adjustment. A total of 1009 participants [mean age 67.2 (10.8) years, male to female ratio 1.3] were recruited from 170 centres, 693 (69%) of which were from across Europe and the remaining 316 (31%) from the USA. At the time of enrolment, participants were taking dronedarone (51%) or other AADs (49%) [flecainide or propafenone (42%), sotalol (11%), and amiodarone (47%)]. No significant differences in the risk of first confirmed AF recurrence with dronedarone vs. other AADs [crude hazard ratio (HR) 1.10 (95% confidence interval 0.85-1.42); adjusted HR 1.16 (0.87-1.55)] were found, irrespective of whether univariate or multivariate models were used. Reported safety events were in accordance with the known safety profile of dronedarone. CONCLUSION: In this population of patients from either Europe or the USA receiving dronedarone or another AAD, the effectiveness of dronedarone was comparable to that observed for other AADs in preventing first AF recurrence.

Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France - a cohort study using the French National Healthcare database (SNDS).

Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2-33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.

Patient characteristics, treatment patterns, and adherence to lipid-lowering therapies following an acute coronary syndrome.

Despite dyslipidaemia management guidelines, many patients do not reach low-density lipoprotein cholesterol targets due to insufficiently intensive regimens or lack of adherence to their medication. This was a retrospective cohort study on the Pharmacoepidemiologic General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Patients included were ≥ 18 years old who suffered an ACS between 2013 and 2016, and treated with lipid-lowering therapy (LLT) at hospital discharge or within 92 days. Patients were followed up to 12 months' post index ACS, a new cardiovascular event, loss to follow-up or death. Treatment intensity (high, moderate and low intensity statins ± ezetimibe) and adherence (proportion of days covered > 80%) are described. A total of 2,695 patients were included; mean age [SD] was 63.1 [12.8] years, and 77% were men. High, moderate and low intensity statins were started in 56% (1,520), 36% (971), and 3% (86) of patients, respectively. A further 2% (46) were on statin/ezetimibe combination, 2% (42) on other LLT and 1% (30) on ezetimibe alone. At follow-up, around 70% of patients were adherent to LLT, with those on moderate intensity treatments showing better adherence (76%) than those on low (63%) or high (67%) intensity treatments. Despite guideline recommendations, many patients following an ACS are not treated with high intensity statins, and adherence remains far from optimal. Effort should be made to increase the proportion of patients treated with high intensity statins following an ACS and to further improve treatment adherence.

Assessing Quality of Life, Economic Burden, and Independence Across the Alzheimer's Disease Continuum Using Patient-Caregiver Dyad Surveys.

Background: Alzheimer's disease (AD) and mild cognitive impairment (MCI) have negative quality of life (QoL) and economic impacts on patients and their caregivers and may increase along the disease continuum from MCI to mild, moderate, and severe AD. Objective: To assess how patient and caregiver QoL, indirect and intangible costs are associated with MCI and AD severity. Methods: An on-line survey of physician-identified patient-caregiver dyads living in the United States was conducted from June-October 2022 and included questions to both patients and their caregivers. Dementia Quality of Life Proxy, the Care-related Quality of Life, Work Productivity and Activity Impairment, and Dependence scale were incorporated into the survey. Regression analyses investigated the association between disease severity and QoL and cost outcomes with adjustment for baseline characteristics. Results: One-hundred patient-caregiver dyads were assessed with the survey (MCI, n = 27; mild AD, n = 27; moderate AD, n = 25; severe AD, n = 21). Decreased QoL was found with worsening severity in patients (p < 0.01) and in unpaid (informal) caregivers (n = 79; p = 0.02). Dependence increased with disease severity (p < 0.01). Advanced disease severity was associated with higher costs to employers (p = 0.04), but not with indirect costs to caregivers. Patient and unpaid caregiver intangible costs increased with disease severity (p < 0.01). A significant trend of higher summed costs (indirect costs to caregivers, costs to employers, intangible costs to patients and caregivers) in more severe AD was observed (p < 0.01). Conclusions: Patient QoL and functional independence and unpaid caregiver QoL decrease as AD severity increases. Intangible costs to patients and summed costs increase with disease severity and are highest in severe AD.

Survival of patients with chronic acid sphingomyelinase deficiency (ASMD) in the United States: A retrospective chart review study.

Background: Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease type A, A/B, and B, is a rare lysosomal storage pathology with multisystemic clinical manifestations. The aims of this study were to estimate the survival probability in patients in the United States with chronic ASMD (ASMD types B and A/B), and to describe the disease characteristics of these patients. Methods: This observational retrospective study included medical chart records of patients with chronic ASMD with retrievable data abstracted by 69 participating physicians from 25 medical centers in the United States. Included patients had a date of ASMD diagnosis or first presentation to a physician for ASMD symptoms (whichever occurred first) between January 01, 1990, and February 28, 2021. Medical chart records were excluded if patients were diagnosed with ASMD type A. Eligible medical chart records were abstracted to collect demographic, medical and developmental history, and mortality data. Survival outcomes were analyzed using Kaplan-Meier survival analyses from birth until death. Results: The overall study population (N = 110) included 69 patients with ASMD type B, nine with type A/B, and 32 with ASMD "non-type A" (ASMD subtype was unknown, but patients were confirmed as not having ASMD type A). The majority of patients were male with a median age at diagnosis of 3.8 years. Thirty-eight patients died during the study observation period, at a median age of 6.8 years. The median (95% confidence interval) survival age from birth was 21.3 (10.2; 60.4) years. At diagnosis or first presentation, 42.7% patients had ≥1 ASMD-related complication; splenic (30.0%) and hepatobiliary (20.9%) being the most common, and 40.9% required ≥1 medical visit due to complications. Conclusion: Patients with chronic ASMD in the United States have poor survival and significant burden of illness.

Assessing out-of-pocket expenses and indirect costs for the Alzheimer disease continuum in the United States.

BACKGROUND: The societal costs of Alzheimer disease (AD) are considerable. Cost data stratified by cost category (direct and indirect) and AD severity in the United States are limited. OBJECTIVE: To describe out-of-pocket (OOP) expenses and indirect costs from unpaid caregiving and work impairment among patients with AD by severity and among patients with mild cognitive impairment (MCI) in a representative sample of the US population. METHODS: Data from the Health and Retirement Study (HRS) were used. HRS respondents were included if they reported an AD diagnosis or were considered as having MCI based on their cognitive performance. MCI and AD severity staging was performed using a crosswalk from results of the modified Telephone Interview of Cognitive Status to the Mini-Mental State Examination. OOP expenses were assessed along with indirect costs (costs to caregivers from providing unpaid help and costs to employers). Sensitivity analyses were performed by varying assumptions of caregiver employment, missed workdays, and early retirement. Patients with AD were stratified by nursing home status, type of insurance, and income level. All cost calculations applied sampling weights. RESULTS: A total of 18,786 patients were analyzed. Patients with MCI (n = 17,885) and AD (n = 901) were aged 67.8 ± 10.7 and 80.9 ± 9.3 years, were 55.7% and 63.3% female, and were 28.3% and 0.9% employed, respectively. OOP expenses per patient per month increased with AD severity, ranging from $420 in mild to $903 in severe AD but were higher in MCI ($554) than in mild AD. Indirect costs to employers were similar across the AD continuum ($197-$242). Costs from unpaid caregiving generally increased by disease severity, from $72 (MCI) to $1,298 (severe AD). Total OOP and indirect costs increased by disease severity, from $869 (MCI) to $2,398 (severe AD). Sensitivity analysis assuming nonworking caregivers and zero costs to employers decreased the total OOP and indirect costs by 32%-53%. OOP expenses were higher for patients with AD who had private insurance (P < 0.01), had higher incomes (P < 0.01), or were in nursing homes (P < 0.01). Indirect costs to caregivers were lower for patients with AD in nursing homes ($600 vs $1,372, P < 0.01). Total indirect costs were higher for patients with AD with lower incomes ($1,498 vs $1,136, P < 0.01) and for those not in nursing homes ($1,571 vs $799, P < 0.01). CONCLUSIONS: This study shows that OOP expenses and indirect costs increase with AD severity, OOP expenses increase with higher income, subscription of private insurance, and nursing home residency, and total indirect costs decrease with higher income and nursing home residency in the United States. DISCLOSURES This study was financially sponsored by Eisai. Drs Zhang and Tahami are employees of Eisai. Drs Chandak, Khachatryan, and Hummel are employees of Certara; Certara is a paid consultant to Eisai. The views expressed here are those of the authors and are not to be attributed to their respective affiliations. Laura De Benedetti, BSc, provided medical writing support to the manuscript; she is an employee of Certara.

Low Molecular Weight Heparin Treatment Patterns and Outcomes in Cancer Patients with Acute Venous Thromboembolism: A Nationwide Cohort Study in France.

Patients with cancer have an increased risk of developing venous thromboembolism (VTE) and an increased risk of death from VTE. Until recently, the standard of care for treatment of VTE in cancer patients was low molecular weight heparins (LMWH). To determine treatment patterns and outcomes, we performed an observational study using a nationwide health database. Treatment patterns, rates of bleeding, and VTE recurrence at 6 and 12 months were assessed in cancer patients with VTE in France prescribed LMWH in 2013-2018. Of 31,771 patients administered LMWH (mean age 66.3 years), 51.0% were male, 58.7% had pulmonary embolism, and 70.9% had metastatic disease. At 6 months LMWH persistence was 81.6%, VTE recurrence had occurred in 1256 patients (4.0%) at a crude rate per 100 person-months (PM) of 0.90, and bleeding had occurred in 1124 patients (3.5%) at a crude rate per 100 PM of 0.81. At 12 months, VTE recurrence had occurred in 1546 patients (4.9%) at a crude rate per 100 PM of 0.71 and bleeding had occurred in 1438 patients (4.5%) at a crude rate per 100 PM of 0.66. Overall, VTE-related clinical event rates were high among patients administered LMWH, suggesting an unmet medical need.

Direct Oral Anticoagulant (DOAC) Dosing in Patients with Non-valvular Atrial Fibrillation (NVAF) in the United Kingdom: A Retrospective Cohort Study Using CPRD Gold Database.

INTRODUCTION: Per-label dosing of direct oral anticoagulants (DOACs) is important for the prevention of stroke and systemic embolism among patients with non-valvular atrial fibrillation (NVAF), especially those with poor renal function, advanced age, low body weight or concomitant P-glycoprotein inhibitors. The study described DOAC use and dosing patterns in patients with NVAF in the UK. METHODS: Using Clinical Practice Research Datalink (CPRD Gold), patients' profiles were described at DOAC initiation (1 January 2016-31 March 2021) and followed for a mean [standard deviation (SD)] 2 (1) years. Patients were categorised as under-dosing: received a lower dose with no indication for a reduced dose; over-dosing: received a standard dose with an indication for a reduced dose; per-label dosing, according to Summary Product Characteristics (SmPC). RESULTS: Forty thousand seven hundred forty-four adult patients with NVAF were identified (mean age: 75.3 (11.2) years; males: 55.4%); 22,827 (56.0%) initiated treatment with apixaban, 930 (2.3%) dabigatran, 5633 (13.8%) edoxaban and 11,354 (27.9%) rivaroxaban. Baseline Charlson comorbidity index ≥ 4 was 65.1%; CHA2DS2-VASc score ≥ 4 was 22.5%; HAS-BLED score ≥ 3 was 18.3%; ~ 2% had prior major bleed and 4.4% a stroke ≤ 2 years before DOAC initiation. Overall, 18.0% of patients received incorrect dosing (~ one in five). Under-dosing was highest for dabigatran (156, 16.8%) and over-dosing was highest for rivaroxaban (1084, 9.6%). Per-label dosing was highest for edoxaban (4773, 84.7%), followed by apixaban (18,756, 82.2%), rivaroxaban (9161, 80.7%) and dabigatran (732, 78.7%). Treatment persistence (no switching or discontinuation) was 79% among edoxaban users, followed by 75% for apixaban, 69% for rivaroxaban and 62% for dabigatran. About 15% of dabigatran users, 10% of rivaroxaban users, 5% of apixaban users and 4% of edoxaban users switched treatment to another DOAC during follow-up. CONCLUSION: Although most patients received per-label dosing, ~ one in five patients was incorrectly dosed with DOAC, which may lead to serious clinical consequences and increased healthcare burden.

Does general practice reduce health inequalities? Analysis of quality and outcomes framework data.

BACKGROUND: The government set a series of targets to reduce health inequalities in England by 2010. Primary care has an important role in reducing health inequalities. The aim of the study was to assess the impact of general practice on reducing area-based health inequalities. METHODS: Analysis of differences in achievement on clinical indicators between practices in Spearhead and non-Spearhead Primary Care Trusts (PCTs) using data from the Quality and Outcomes Framework (QOF) for 2004/05 and 2005/06, practice characteristics and Spearhead status of PCTs. The study used data on 8339 primary care practices in England. Unweighted mean reported achievement on subset of 26 clinical indicators was calculated. The study analysed differences in achievement by Spearhead status and deprivation in both years and the change between years. Multiple regression analysis of relationship between Spearhead status, income deprivation, reported achievement and other factors also were carried out. RESULTS: Practices in Spearhead PCTs performed worse than practices in non-Spearhead PCTs in both years but showed greater improvement. Among the most deprived practices, there were no differences in QOF achievement between Spearhead and non-Spearhead PCTs. Previous year's achievement was the strongest predictor of performance. CONCLUSION: The narrowing in performance between practices in Spearhead and non-Spearhead PCTs may have indirectly contributed to a reduction in area-based health inequalities but the differences are small. The lack of difference between the most deprived practices in Spearhead and non-Spearhead PCTs suggest that area-based initiatives to tackle inequalities have not yet had an observable impact on deprived practices. Unobserved factors explain most of the variation in achievement.

Comparative Analysis of All-Cause Health Care Resource Utilization and Costs Among Venous Thrombosis Patients Without Cancer Prescribed Apixaban or VKAs in France.

INTRODUCTION: The direct oral anticoagulant (DOAC) apixaban has shown to have non-inferior efficacy and better safety than vitamin K antagonists (VKAs) in patients with venous thromboembolism (VTE). We determined whether healthcare resource use (HCRU) and direct all-cause medical and non-medical costs in patients with VTE in France differed between VKAs and apixaban. METHODS: A retrospective cohort study was conducted using French national health data from January 2013-June 2018 for anticoagulant-naïve adults hospitalized with VTE. All-cause costs and HCRU per patient per month (PPPM) were compared between apixaban and VKA cohorts created by 1:1 propensity score matching. Two-part models with bootstrapping were used to calculate marginal effects for costs and HCRU. RESULTS: The matched VKA and apixaban cohorts each comprised 7503 patients. Compared to VKAs, patients prescribed apixaban had significantly lower (P < 0.0001) mean all-cause costs PPPM for outpatient visits (€438.54 vs. €455.58), overall laboratory tests (€21.26 vs. €83.73), and hospitalizations (€249.48 vs. €343.82), but significantly higher (P < 0.0001) mean all-cause costs PPPM for overall drugs (€97.06 vs. €69.56) and medical procedures (€42.12 vs. €35.50). Mean total all-cause direct medical costs (€687.93 vs. €798.70) and total all-cause direct medical and non-medical costs (€771.60 vs. €883.66) were significantly lower (P < 0.0001) for apixaban. Mean HCRU PPPM showed similar trends. Subgroup analyses showed that, among patients with recurrent VTE, patients prescribed apixaban had significantly lower (P < 0.0001) all-cause costs PPPM for total medical costs (€17.26 vs. €18.12) and total all-cause direct medical and non-medical costs (€18.37 vs. €19.20) than patients prescribed VKAs. Similarly, among patients with bleeding, patients prescribed apixaban had significantly lower (P < 0.0001) all-cause costs PPPM for total medical costs (€15.34 vs. €32.61) and total all-cause direct medical and non-medical costs (€16.23 vs. €34.63) than patients prescribed VKAs. CONCLUSION: Compared to VKAs, apixaban may be cost-saving in the treatment of patients hospitalized for acute VTE.

Effectiveness and Safety of Oral Anticoagulants in the Treatment of Acute Venous Thromboembolism: A Nationwide Comparative Cohort Study in France.

INTRODUCTION: Data from clinical trials indicate that direct oral anticoagulants (DOACs) are noninferior and safer than conventional therapy (low-molecular-weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting. METHODS: This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013 to 2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional hazards regression was used to estimate adjusted hazard ratios of the endpoints. RESULTS: A total of 58,137 patients were included (10,775 VKAs, 10,440 apixaban, 36,922 rivaroxaban). Propensity score-matched cohort sizes were 7,503 for apixaban and 9,179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32-0.59]), all-cause death (0.61 [0.51-0.74]), and first recurrent VTE (0.67 [0.52-0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53-0.74]) but not for bleeding requiring hospitalization (0.86 [0.69-1.07]) or first recurrent VTE (0.91 [0.74-1.13]). CONCLUSION: Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.

Exploring the treatment gap among patients with osteoporosis-related fractures in France.

The use of anti-osteoporosis treatment following a diagnosis of osteoporosis with fracture or a relevant fragility fracture remains low in France. Initiating an anti-resorptive may reduce the incidence of a subsequent fracture by 60%. PURPOSE: To describe real-world osteoporosis treatment patterns in individuals with a fragility fracture in France and to explore the impact of initiating treatment on the risk of subsequent fracture. METHODS: A retrospective cohort study, using the national French Health Insurance claims database. Males and females 50 years and over, with a hospital discharge diagnosis of osteoporosis with fracture or a relevant fragility fracture between 2011 and 2014, were included and followed until death or the end of 2016, whichever came first. The primary outcome was the proportion of patients receiving anti-osteoporosis treatments prior to and post-index fracture. Change in fracture rates before and after treatment initiation was assessed in an exploratory analysis. RESULTS: A total of 574,133 patients (138,567 males, 435,566 females) had a qualifying index fracture. The proportion of patients receiving any anti-osteoporosis treatment increased pre-index fracture to post-index fracture from 2.2 to 5.6% among males, and from 11.8 to 18.2% among females. Oral bisphosphonates were the most prescribed anti-osteoporosis treatment for both males and females among post-index fractures (60.6% and 68.8% of patients initiating treatment). Following initiation of anti-resorptives, the incidence of subsequent fracture was reduced by 60% (rate ratio (RR): 0.40, 95% confidence interval [CI]: 0.34-0.45). CONCLUSION: Anti-osteoporosis treatment following an index fracture in France remains low. Improved identification and pharmacologic management of patients at risk of fragility fractures are necessary to reduce the risk of subsequent fractures.

Real-world Adherence to Nusinersen in Adults with Spinal Muscular Atrophy in the US: A Multi-site Chart Review Study.

Limited evidence exists on real-world adherence to nusinersen for the treatment of spinal muscular atrophy (SMA). Data are presented from a multi-site retrospective chart review of 86 adults with SMA initiating nusinersen at nine US centers between January 2017 and February 2019. Seventy-nine (92%) adults remained on nusinersen during the study; 454 (92%) of 493 total nusinersen doses were received on time. Fifty-eight (67%) adults received all nusinersen doses on time. The majority of patients with at least one nonadherent dose resumed nusinersen on time. Most patients followed the dosing schedule across the loading and maintenance dose periods.

Association of Treatment Intensity and Adherence to Lipid-Lowering Therapy with Major Adverse Cardiovascular Events Among Post-MI Patients in Germany.

INTRODUCTION: Patients with a history of myocardial infarction (MI) are at very high risk of subsequent cardiovascular events. This study evaluated the association of treatment intensity and adherence to lipid-lowering therapies (LLT) with major adverse cardiovascular events (MACE) among post-MI patients in Germany. METHODS: We carried out a retrospective cohort study using German health claims data (2010-2015). We included patients ≥ 18 years, with a history of MI and who started an LLT (statin and/or ezetimibe), between 2011 and 2013. The follow-up period started 1 year after the second LLT prescription and continued until MACE, all-cause death or December 31, 2015, whichever occurred first. Treatment intensity was classified based on expected low-density lipoprotein cholesterol reduction; adherence was measured by the proportion of days covered using prescription data. A combined adherence-adjusted intensity variable was created by multiplying intensity and adherence. We used Cox proportional hazards models to control for age, sex, Charlson Comorbidity Index and other cardiovascular risk factors at baseline. RESULTS: A total of 14,944 patients were included. Mean age was 66.7 (SD = 13.0) years; 68.7% of patients were men. Each 10% increase in treatment intensity, adherence, or adherence-adjusted intensity was associated with a decrease in the risk of MACE of 17% (HR = 0.83, 95% CI 0.79-0.87), 5% (HR = 0.95, 95% CI 0.94-0.97), and 14% (HR = 0.86, 95% CI 0.83-0.90), respectively. CONCLUSIONS: Higher treatment intensity and/or adherence of LLT was associated with significantly lower risk of MACE in post-MI patients. Strategies to tailor intensity to patient profiles and improve adherence could reduce the risk of cardiovascular events.

Clinical impact and room for improvement of intensity and adherence to lipid lowering therapy: Five years of clinical follow-up from 164,565 post-myocardial infarction patients.

BACKGROUND: In patients at risk of cardiovascular (CV) events, the effectiveness of lipid-lowering therapies (LLT) is affected by both intensity and adherence. Our study evaluated the association between LLT intensity (statin and/or ezetimibe) and adherence, and CV events in patients with a history of myocardial infarction (MI) in France. METHODS: Using the French national healthcare database (SNDS), we included patients with a history of MI, an initial LLT prescription in 2011-2013, and a second prescription within one year. LLT intensity was defined using the expected percent reduction in low-density lipoprotein cholesterol; adherence was measured as the proportion of days covered. Cox proportional hazards models were used to assess associations between intensity and/or adherence, and the risk of major adverse CV event (MACE). RESULTS: 164,565 patients were included; mean (SD) age, 66·3 (13·8) years; 73·6% men. Following an MI, only half of patients were treated with high-intensity LLT and approximately 40% of those on LLT remained non-adherent during follow-up (mean (SD) follow-up, 2·6 (1·4) years). Each 10% increase in treatment intensity, adherence, or adherence-adjusted intensity was respectively associated with a 16% (HR 0.84, 95%CI 0.84-0.85), 7% (HR 0.93, 95%CI 0.93-0.94), and 15% (HR 0.85, 95%CI 0.84-0.86) decrease in the risk of MACE. CONCLUSIONS: Among patients with a history of MI, prescriptions of high-intensity LLT were limited and adherence to LLT was low. Higher intensity and/or adherence to statins was associated with a significantly lower risk of MACE, highlighting the importance of compliance with clinical guidelines to improve patient outcomes.

A review of the public health impact of the Quality and Outcomes Framework.

There are clear policy objectives in England to encourage primary care and general practice to address health inequalities. In this paper we explore the potential impact of the Quality and Outcomes Framework (QOF) on health inequalities and review the available evidence including analysis of the area based differences in performance between practices in Spearhead and non-Spearhead areas. Overall, the evidence suggests that differences in performance, as measured by the QOF, between practices in deprived and non-deprived areas are narrowing. Although QOF achievement improved in all practices there is weak evidence as to the impact of the QOF on health. The evidence is equivocal as to whether improvements in clinical care and the narrowing gap in performance are influenced by the incentives created by the QOF or whether this translates into reduced health inequalities. Even though the QOF is only part of the range of incentives which affects practices, it is vital that indicators are aligned to the objective of reducing health inequalities. Additional research is needed to understand whether the QOF ensures that those who are the most difficult to reach and those whose need of care is greatest are getting access to high quality primary care and whether in turn it will succeed in reducing health inequalities.