Characterization and LDL-C management in a cohort of high and very high cardiovascular risk patients: The PORTRAIT-DYS study.

AIM: This study aims to characterize sociodemographic and clinical characteristics, use of lipid-lowering therapies (LLTs), and low-density lipoprotein cholesterol (LDL-C) control in a population with increased cardiovascular (CV) risk. METHODS: A cross-sectional observational study that uses electronic health records of patients from one hospital and across 14 primary care health centers in the North of Portugal, spanning from 2000 to 2020 (index date). Patients presented at least (i) 1 year of clinical data before inclusion, (ii) one primary care appointment 3 years before the index date, and (iii) sufficient data for CV risk classification. Patients were divided into three cohorts: high CV risk; atherosclerotic cardiovascular disease (ASCVD) risk equivalents without established ASCVD; evidence of ASCVD. CV risk and LDL-C control were defined by the 2019 and 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidemia guidelines. RESULTS: A total of 51 609 patients were included, with 23 457 patients classified as high CV risk, 19 864 with ASCVD equivalents, and 8288 with evidence of ASCVD. LDL-C control with 2016 ESC/EAS guidelines was 32%, 10%, and 18% for each group, respectively. Considering the ESC/EAS 2019 guidelines control level was even lower: 7%, 3%, and 7% for the same cohorts, respectively. Patients without any LLT prescribed ranged from 37% in the high CV risk group to 15% in patients with evidence of ASCVD. CONCLUSION: We found that LDL-C control was very low in patients at higher risk of CV events. An alarming gap between guidelines on dyslipidemia management and clinical implementation persists, even in those at very high risk or with established ASCVD.

Estimating Prevalence and Characteristics of Statin Intolerance among High and Very High Cardiovascular Risk Patients in Germany (2017 to 2020).

Statin intolerance (SI) (partial and absolute) could lead to suboptimal lipid management. The lack of a widely accepted definition of SI results into poor understanding of patient profiles and characteristics. This study aims to estimate SI and better understand patient characteristics, as reflected in clinical practice in Germany using supervised machine learning (ML) techniques. This retrospective cohort study utilized patient records from an outpatient setting in Germany in the IQVIA™ Disease Analyzer. Patients with a high cardiovascular risk, atherosclerotic cardiovascular disease, or hypercholesterolemia, and those on lipid-lowering therapies between 2017 and 2020 were included, and categorized as having "absolute" or "partial" SI. ML techniques were applied to calibrate prevalence estimates, derived from different rules and levels of confidence (high and low). The study included 292,603 patients, 6.4% and 2.8% had with high confidence absolute and partial SI, respectively. After deploying ML, SI prevalence increased approximately by 27% and 57% (p < 0.00001) in absolute and partial SI, respectively, eliciting a maximum estimate of 12.5% SI with high confidence. The use of advanced analytics to provide a complementary perspective to current prevalence estimates may inform the identification, optimal treatment, and pragmatic, patient-centered management of SI in Germany.

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.

Treatment and low-density lipoprotein cholesterol levels in patients with hypercholesterolaemia or mixed dyslipidaemia at high or very high cardiovascular risk: a population-based cross-sectional study in the Netherlands.

OBJECTIVE: To describe treatment patterns, low-density lipoprotein cholesterol (LDL-C) levels and healthcare resource utilization (HCRU) in the Netherlands in 2018 of patients with hypercholesterolaemia or mixed dyslipidaemia at high or very high cardiovascular (CV) risk. METHODS: From the PHARMO Database Network adult patients with a diagnosis or receiving lipid lowering therapy (LLT) between 2009 and 2018 were selected. Patients at high or very high CV risk according to 2016 ESC/EAS guidelines with recorded LDL-C levels who were treated with LLT or were characterized as statin intolerant in 2018 were included. LLT treatment patterns, LDL-C levels and HCRU (General Practitioner [GP] consultations and hospitalizations) were assessed. RESULTS: The study population included 54,346 patients, of which 70% were at very high CV risk and 30% at high CV risk. The majority (93%) received statin monotherapy, mostly of moderate (73%) or high (15%) intensity. Only 3% received a combination of statin and ezetimibe. Statin intolerance, based on a treatment algorithm, was estimated at 3%. Average LDL-C decreased with LLT intensity. Overall, 74% reached LDL-C < 2.5 mmol/l and 34% <1.8 mmol/l with their current treatment, and 46% reached their LDL-C goal according to 2016 ESC/EAS guidelines. The highest rates of hospitalizations and GP consultations, including home visits, were recorded in patients with peripheral artery disease or polyvascular disease. CONCLUSION: The treatment of hypercholesterolaemia and mixed dyslipidaemia in patients at high or very high CV risk in the Netherlands was suboptimal in 2018. To further lower CV risk alternative treatment strategies using add-on therapies are needed.

Cost-utility analysis of increasing uptake of universal seasonal quadrivalent influenza vaccine (QIV) in children aged 6 months and older in Germany.

Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (€6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually €20.5 million and €731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society.

What is the context? Every winter, millions of people in Europe become ill due to influenza (flu), and some need to be hospitalized for complications that can sometimes lead to death.While mainly older adults and people with chronic illness are at higher risk of complications from influenza, children have the highest risk of infection and of transmitting the disease.Current vaccination policies in Europe, including Germany, target older adults and high-risk populations (pregnant women, children and other age groups with chronic diseases).What is new? This analysis simulates the effects of expanding current German vaccination programs in high-risk children to include healthy children, and of increasing vaccination coverage rates, for direct protection against infection, and to reduce the disease transmission in the rest of the population.We modeled three vaccination strategies: vaccinating 40% of all (healthy and high- risk) children under 5 years old;vaccinating 40% of all (healthy and high-risk) children under 18 years old;vaccinating 90% of high-risk children under 18 years old.What is the impact? All three strategies resulted in health gains, as more influenza cases, complications and deaths were prevented in all age groups of the population compared to the current situation.The strategies targeting both healthy and high-risk children provided the greatest health benefits. In particular, a vaccination policy targeting all children under 18 years old was predicted to provide the most health benefits as well as the highest cost savings: the increased costs of vaccination were more than offset by the savings in disease management costs as a result of having fewer influenza patients.Vaccinating healthy children against influenza is expected to significantly reduce the disease burden in the total population while saving costs, due to reduced transmission of the disease.

Lipid management across Europe in the real-world setting: a rapid evidence review.

OBJECTIVE: To provide a contemporary overview of recent real-world lipid-lowering therapy (LLT) practices and outcomes in patients with hypercholesterolemia/dyslipidemia at high/very high risk of atherosclerotic cardiovascular disease in Europe. METHODS: A structured literature review of recent (July 2015-July 2020) real-world studies reporting lipid management and outcomes was conducted using a rapid evidence synthesis. Outcomes included patient characteristics, LLT treatment practices, adherence and low-density lipoprotein cholesterol (LDL-C) goal attainment. RESULTS: Fifty-three real-world observational studies in high/very high risk patients were selected after screening 5664 records (n = 50 national [sample size range 38-237,279] and n = 3 multinational studies [sample size range 6648-8456]). Mean age ranged from 33 to 77 years; hypertension, diabetes and obesity were commonly reported comorbidities. Statins were the most common LLT; patients without familial hypercholesterolemia (FH) mostly received high or moderate intensity statins/LLT, while patients with FH mostly received high intensity statins/LLT. The proportion of patients receiving ezetimibe was low overall (ezetimibe + statin use in those with and without familial hypercholesterolemia [FH] range 5%-59% and 1%-22%, respectively). Overall, the use of proprotein convertase subtilisin/kexin 9 inhibitor (PCSK9i) therapy was limited. Adherence to LLT therapies was defined variably and ranged from 46%-92%. LDL-C goal attainment was suboptimal, irrespective of LLT (overall range in goal attainment with oral LLT was 2%-73% [FH: 2%-23%] and with PCSK9i was 20%-65%). CONCLUSIONS: LDL-C control is suboptimal and the available LLT armamentarium, most importantly combination therapy, is being underutilized in high/very high risk patients leading to inadequate management of cardiovascular risk.

Assessing direct and indirect effects of pediatric influenza vaccination in Germany by individual-based simulations.

Children have a high burden of influenza and play a central role in spreading influenza. Routinely vaccinating children against influenza may, thus, not only reduce their disease burden, but also that of the general population, including the elderly who frequently suffer severe complications. Using the published individual-based tool 4Flu, we simulated how pediatric vaccination would change infection incidence in Germany. Transmission of four influenza strains was simulated in 100,000 individuals with German demography and contact structure. After initialization with the recorded trivalent influenza vaccination coverage for 20 years (1997-2016), all vaccinations were switched to quadrivalent influenza vaccine (QIV). Scenarios where vaccination coverage of children (0.5-17-year-old) was increased from the current value (4.3%) to a maximum of 10-60% were compared to baseline with unchanged coverage, averaging results of 1,000 pairs of simulations over a 20-year evaluation period (2017-2036). Pediatric vaccination coverage of 10-60% annually prevented 218-1,732 (6.3-50.5%) infections in children, 204-1,961 (2.9-28.2%) in young adults and 95-868 (3.1-28.9%) in the elderly in a population of 100,000 inhabitants; overall, 34.1% of infections in the total population (3.7 million infections per year in Germany) can be prevented if 60% of all children are vaccinated annually. 4.4-4.6 vaccinations were needed to prevent one infection among children; 1.7-1.8 were needed to prevent one in the population. Enhanced pediatric vaccination prevents many infections in children and even more in young adults and the elderly.

Cost-effectiveness of the recombinant zoster vaccine in the German population aged ≥60 years old.

Each year, around 300,000 Herpes Zoster (HZ) cases are observed in the German population, resulting in costs over €182 million to society. The objective of this study was to estimate the potential public health and economic impact of the new Adjuvanted Recombinant Zoster Vaccine (RZV, Shingrix) in the German population ≥ 60 years of age (YOA) and to identify the optimal age of vaccination. We used a static, multi-cohort Markov model that followed a hypothetical cohort of 1 million people ≥ 60 YOA life-long after vaccination using German-specific inputs. Both costs and outcomes were discounted at 3%, the incremental cost-effectiveness ratio (ICER) was calculated based on the societal perspective. The coverage of RZV was set at 40% with a second-dose compliance of 70%. Vaccinating the population aged ≥ 60 YOA would result in 45,000 HZ cases avoided, 1,713 quality-adjusted life years (QALYs) gained at a total cost of approximately €63 million compared to 38,000 cases avoided, 1,545 QALYs gained at a total cost of approximately €68 million in the population ≥ 70 YOA. This would result in an ICER of approximately €37,000 and €44,000/QALY, for the age cohort ≥ 60 and ≥ 70 YOA, respectively. Scenario analyses demonstrated that vaccinating at age 60 or 65 YOA would show greater public health impact and would result in the lowest observed ICER compared to vaccinating at 70 YOA. In conclusion, starting vaccination with RZV in the German population ≥ 60 YOA would demonstrate the best value from a public health and economic standpoint.

Impact of herpes zoster and postherpetic neuralgia on the quality of life of Germans aged 50 or above.

BACKGROUND: Herpes zoster (HZ) is a painful dermatomal rash caused by reactivation of latent varicella zoster virus surviving in the patient's sensory ganglia after a previous episode of varicella. The incidence of HZ increases markedly with age as does the proportion of HZ patients who develop postherpetic neuralgia (PHN) with often severe and debilitating pain persisting for months and even years. This prospective study aimed to assess the impact of HZ and PHN on the quality of life (QoL) of individuals aged ≥ 50 years in Germany. METHODS: Patients were recruited when consulting primary care physicians for a first HZ episode. PHN was defined as a 'worst' pain score ≥ 3 on the Zoster Brief Pain Inventory (ZBPI) scale persisting or appearing 90 days or more after rash onset. PHN-cases were followed for up to nine months after rash onset. The interference of pain with patients' ability to carry out normal activities was assessed by the ZBPI activities of daily living (ADL) scale and QoL by the EuroQoL five-dimension scale (EQ-5D) utility score. RESULTS: Of 513 patients enrolled, 61 (11.9%) developed PHN. At HZ onset, the mean ZBPI worst pain score of all patients was 5.1, the least square (LS)means estimates of the ZBPI ADL and EQ-5D utility scores were 2.970 and 0.740, respectively. Over three months follow-up, the pain scores decreased and the QoL increased monotonically across all age groups. At Day 90, the mean ZBPI worst pain score of the PHN patients was 4.4, while the LSmeans estimates of the ZBPI ADL and EQ-5D utility scores were 2.899 and 0.826, respectively. For patients with PHN persisting at nine months, the pain scores and QoL remained unchanged over the six months following the development of PHN. CONCLUSION: HZ and PHN had a substantial impact on the patients' QoL and ability to function in their normal activities. There was a clear association in time between the evolution of pain and estimated QoL. The impact on ADL and QoL did not vary with age.

Incidence and costs of herpes zoster and postherpetic neuralgia in German adults aged ≥50 years: A prospective study.

OBJECTIVES: Herpes zoster (HZ) mainly affects elderly people and immunocompromised individuals. HZ is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain. This study aimed to estimate the HZ incidence in individuals aged ≥50 years in Germany, the proportion of PHN and the economic burden. METHODS: From 2010 to 2014, HZ patients were recruited when consulting physicians in physician networks covering about 157,000 persons aged ≥50 years. PHN was defined as "worst pain" rated ≥3 on the zoster brief pain inventory persisting or appearing over 90 days after rash onset. Costs were calculated based on medical resource utilization and lost working time. RESULTS: HZ incidence was estimated as 6.7/1000 person-years, increasing with age to 9.4/1000 in ≥80 year-olds. Among 513 HZ patients enrolled, the proportion of PHN was 11.9%, rising with age to 14.3% in HZ patients ≥80 years. Estimated total cost per HZ patient was €156 from the healthcare system perspective and €311 from the societal perspective. CONCLUSIONS: The study confirmed previous findings that HZ causes a substantial clinical and economic burden in older German adults. It also confirmed the age-related increasing risk of HZ and PHN.

German travelers' preferences for travel vaccines assessed by a discrete choice experiment.

BACKGROUND: Many travelers to regions with endemic infectious diseases do not follow health authorities' recommendations regarding vaccination against vaccine-preventable infectious diseases, before traveling. The determinants of individual travelers' decisions to vaccinate before traveling are largely unknown. This study aimed to provide this information using a discrete choice experiment (DCE) administered to four types of German travelers: (1) business travelers; (2) travelers visiting friends and relatives (VFR); (3) leisure travelers; and (4) backpackers. METHODS: A DCE survey was developed, pretested and administered online. It included a series of choice questions in which respondents chose between two hypothetical vaccines, each characterized by four disease attributes with varying levels describing the of risk, health impact, curability and transmissibility of the disease they would prevent (described with four disease attributes with varying levels of risk, health impact, curability and transmissibility), and varying levels of four vaccine attributes (duration of protection, number of doses required, time required for vaccination, and vaccine cost). A random-parameters logit model was used to estimate the importance weights each traveler type placed on the various attribute levels. These weights were used to calculate mean monetary equivalents (MMEs) of changes in each attribute (holding all others constant) and of hypothetical disease-vaccine combinations. RESULTS: All traveler types' choices indicated that they attached the greatest importance to the risk and health impact of disease and to the vaccine cost whereas the other disease and vaccine attributes were less important for their decisions about travel vaccines. An option of not choosing any of the vaccine-pairs presented was rarely selected indicating that travelers' generally prefer to be vaccinated rather than not. The MMEs of changes in vaccine attributes indicated a very high variability between the individual travelers within each type. CONCLUSIONS: The travelers' responses indicated strong preferences for selecting vaccination rather than opting out of vaccination, and disease risk, health impact and vaccine cost were the most important features for vaccine choice.

Assessment of the potential public health impact of Herpes Zoster vaccination in Germany.

The aim of this study was to compare the public health impact of introducing 2 Herpes Zoster (HZ) vaccines, Zoster Vaccine Live (ZVL) versus a non-live adjuvanted subunit candidate vaccine (HZ/su), in the German population aged 50+ years split into 3 age cohorts, i.e. 50-59, 60-69 and 70+ years, respectively. A multi-cohort static Markov model was developed following age cohorts over their lifetime. Demographic data were obtained from the German federal statistical office. HZ incidence and the proportion of HZ individuals developing post-herpetic neuralgia (PHN) were derived from German specific sources. Age-specific vaccine efficacy and waning rates were based on published clinical trial data. Vaccine coverage for both vaccines was assumed to be 40%, with compliance of the second dose of the HZ/su vaccine of 70%. Sensitivity analyses were performed to assess the robustness of the results. It was estimated that, over the remaining lifetime since vaccination, the HZ/su vaccine would reduce the number of HZ cases by 725,233, 533,162 and 486,794 in the 3 age cohorts, respectively, compared with 198,477, 196,000 and 104,640, using ZVL. The number needed to vaccinate (NNV) to prevent one HZ case ranged from 8 to 11 using the HZ/su vaccine compared with 20 to 50 using ZVL. Corresponding NNV to prevent one PHN case ranged from 39 to 53 using the HZ/su vaccine compared with 94 to 198 using ZVL. Due to the higher, sustained vaccine efficacy, the candidate HZ/su vaccine demonstrated superior public health impact compared with ZVL.

Cost-Utility of Quadrivalent Versus Trivalent Influenza Vaccine in Germany, Using an Individual-Based Dynamic Transmission Model.

BACKGROUND: Seasonal influenza infection is primarily caused by circulation of two influenza A strain subtypes and strains from two B lineages that vary each year. Trivalent influenza vaccine (TIV) contains only one of the two B-lineage strains, resulting in mismatches between vaccine strains and the predominant circulating B lineage. Quadrivalent influenza vaccine (QIV) includes both B-lineage strains. The objective was to estimate the cost-utility of introducing QIV to replace TIV in Germany. METHODS: An individual-based dynamic transmission model (4Flu) using German data was used to provide realistic estimates of the impact of TIV and QIV on age-specific influenza infections. Cases were linked to health and economic outcomes to calculate the cost-utility of QIV versus TIV, from both a societal and payer perspective. Costs and effects were discounted at 3.0 and 1.5 % respectively, with 2014 as the base year. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: Using QIV instead of TIV resulted in additional quality-adjusted life-years (QALYs) and cost savings from the societal perspective (i.e. it represents the dominant strategy) and an incremental cost-utility ratio (ICUR) of €14,461 per QALY from a healthcare payer perspective. In all univariate analyses, QIV remained cost-effective (ICUR <€50,000). In probabilistic sensitivity analyses, QIV was cost-effective in >98 and >99 % of the simulations from the societal and payer perspective, respectively. CONCLUSION: This analysis suggests that QIV in Germany would provide additional health gains while being cost-saving to society or costing €14,461 per QALY gained from the healthcare payer perspective, compared with TIV.

Cost for physician-diagnosed influenza and influenza-like illnesses on primary care level in Germany--results of a database analysis from May 2010 to April 2012.

BACKGROUND: Seasonal influenza is one of the most significant infectious diseases in Germany; epidemic outbreaks occur every winter and cause substantial morbidity and mortality. However, published data from Germany on the current economic burden of influenza and the costs per episode are lacking. METHODS: A retrospective database analysis was conducted using a longitudinal electronic medical records database (IMS Disease Analyzer). Patients with influenza, diagnosed by German office-based physicians using ICD-10 J09-11 (International Classification of Diseases, 10(th) revision), who were observable in the database from 12 months before the index (diagnosis) date until 1 month afterwards, were included. The selection window, defined to cover two influenza seasons, was May 2010 to April 2012. Direct and indirect costs were evaluated from payer, patient and societal perspectives. Published unit costs and tariffs from Germany (2012) were used for the analysis. RESULTS: A total of 21,039 influenza-attributable episodes in 17,836 adults, managed by primary care physicians (PCP) and 7,107 episodes in 6,288 children, managed by pediatricians, were eligible for analysis. The mean (±Standard Deviation (SD)) age of the adults with at least one episode was 46 (±18) years and 7 (±4) years in the children. The presence of clinical risk factors was documented for 39% episodes in adults and 24% episodes in children, with the most common being cardiovascular diseases in adults (29%) and chronic respiratory diseases in children (23%). Complications and severe symptoms accompanied the influenza-attributable episode (adults: 37%, children: 54%), bronchitis (adults: 16%, children: 19%) and acute upper respiratory infection (adults: 15%, children: 21%) being the most frequent. From a societal perspective, the total average mean cost (±SD) per episode was €514 (±609) in adults, where work days lost were the main cost driver (82%), and €105 (±224) in children. Complications and severe symptoms increased the cost per episode versus episodes without by 1.7 times in adults (€684 (±713) vs. €413 (±510)) and nearly 3 times in children (€149 (±278) vs. €55 (±116)). CONCLUSIONS: Based on a large patient sample derived from representative PCP and pediatricians panels, our results demonstrate that seasonal influenza is associated with substantial clinical and economic burden in Germany.