Vericiguat Use in Patients with Heart Failure in Real-World Settings during the First Year after the Drug Authorization in Japan.

Background: Vericiguat was developed to treat patients with heart failure (HF). Currently, limited data are available to characterize vericiguat-treated patients in real-world clinical settings. Methods: This retrospective cohort study was done using a Japanese hospital administrative database to describe the use of vericiguat in patients with HF in real-world settings. Adult patients diagnosed with HF prescribed vericiguat between 1 July 2021 and 30 September 2022 were included. Patient characteristics at the initiation of vericiguat treatment, patterns of HF medication use, and vericiguat dose titrations were assessed within the first 90 days of treatment. Results: The study included 829 patients who were initiated on vericiguat therapy. The mean age was 75.5 years and 69.0% were male. Hypertension, coronary artery disease, and diabetes mellitus were present in 91.7, 71.3, and 60.1% of patients, respectively. Most patients had previously received HF medications, with high percentages using angiotensin-receptor blocker neprilysin inhibitors (ARNI; 43.9%) and sodium-glucose cotransporter-2 inhibitors (54.4%). During the first 90 days of vericiguat treatment, 65.8% of the patients were uptitrated from their starting dose, and 32.3% had reached the maximal daily dose. The median time to reach the maximal daily dose was 34 days. The multivariable model identified that initiating vericiguat treatment in an outpatient setting and using ARNI before initiating vericiguat treatment were factors significantly associated with reaching the maximal daily dose of vericiguat at any given time, whereas older age, chronic kidney disease, hyperkalemia, and anemia were not associated. Conclusions: These findings provide early insights into the use of vericiguat, which aid in optimizing the combinations and/or sequences of HF treatment incorporating vericiguat therapy.

Treatment Patterns, Outcomes, and Persistence to Newly Started Heart Failure Medications in Patients with Worsening Heart Failure: A Cohort Study from the United States and Germany.

BACKGROUND: Data are limited regarding guideline-directed medical therapy (GDMT) treatment patterns in patients with worsening heart failure (HF). METHODS: We used administrative claims databases in Germany and the USA to conduct a retrospective cohort study of patients with worsening HF. Two cohorts of patients with prevalent HF and a HF hospitalization (HFH) from 2016 to 2019, alive at discharge (N = 75,140 USA; N = 47,003 Germany) were identified. Index date was the first HFH during the study period. One-year HF rehospitalization and mortality rates were calculated and a composite endpoint of both outcomes assessed using Kaplan-Meier estimation. We evaluated HF medication patterns in the 6 months before and after the index date. New users of a HF medication (at discharge/after index HFH) were followed for 1 year to evaluate persistence (no treatment gaps > 2 months) RESULTS: One-year HF rehospitalization rates were 36.2% (USA) and 47.7% (Germany). One year mortality rates were 30.0% (USA) and 23.0% (Germany), and the composite endpoint (mortality/HF rehospitalization) was reached in 55.1 % (USA) and 56.6% (Germany). Kaplan-Meier plots showed the risk for the composite endpoint was high in the early post discharge period. Comparison of patterns pre- and postindex HFH showed some increase in use of mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitor (ARNI), and triple therapy; use of angiotensin-converting enzyme (ACE) inhibitor/ angiotensin receptor blocker (ARB) plus beta-blockers remained constant/slightly declined; < 20% patients received triple therapy (ACE inhibitor/ARB plus beta-blocker plus MRA). A third of patients were new users; 1 year persistence rates were often low. CONCLUSIONS: Morbidity, mortality, and rehospitalization risk is high among patients with worsening HF; uptake and continuation of GDMT is suboptimal.

Initiation and continuation of pharmacological therapies in patients hospitalized for heart failure in Japan.

Currently, the utilization patterns of medications for heart failure (HF) after worsening HF events remain unelucidated in Japan. Here, we conducted a retrospective cohort study evaluating the changes in HF drug utilization patterns in 6 months before and after hospitalizations for HF. The adherence to newly initiated HF medications was evaluated based on the proportion of days covered (PDC) and persistence as continuous treatment episodes among new users. The study included 9091 patients hospitalized for HF between January 2016 and September 2019, including 2735 (30.1%) patients who were newly prescribed at least one HF medication after hospitalization. Despite increases in the use of foundational HF therapy (beta-blockers, angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers, or mineralocorticoid receptor antagonists), 35.6% and 7.6% of patients were treated with the HF foundational monotherapy or diuretics alone after hospitalization, respectively. The mean PDC of newly initiated HF medications ranged from 0.57 for thiazide diuretics to 0.77 for sodium-glucose cotransporter-2 inhibitors. Continuous use of HF medications during the first year after initiation was observed in 30-60% of patients. The mean PDC and one-year continuous HF medication use were consistently lower in patients aged ≥ 75 years and in patients with a history of HF hospitalization for all HF medication classes except for tolvaptan and digoxin. Despite the guideline recommendations of HF pharmacotherapy, both treatment and adherence were suboptimal after HF hospitalization, especially in vulnerable populations such as older patients and those with prior HF hospitalizations.

A real-world analysis of factors associated with high healthcare resource utilization and costs in patients with myasthenia gravis receiving second-line treatment.

Despite current treatments, patients with myasthenia gravis (MG) experience unpredictable and inadequately controlled symptoms, lending to variability in the clinical and economic burden of disease. However, limited data are available on MG healthcare costs, and specifically, no data on patients initiating second-line therapy. Using claims data from the IBM® MarketScan® database, we assessed patient characteristics, healthcare resource utilization, and costs among MG patients initiating second-line therapy, and identified potential factors associated with high healthcare costs over a two-year follow-up period. We identified 1498 patients, of whom 49% and 31% received chronic steroids and non-steroidal immunosuppressants (NSISTs) as their second-line therapy, respectively. During follow-up, 49% experienced ≥1 MG exacerbation. Among all patients, mean all-cause total healthcare cost was $106,821 per patient during follow-up, with $88,040 and $18,780 attributed to medical and pharmacy costs, respectively. In a multivariable analysis, variables significantly associated with high cost included use of high-dose steroids, chronic intravenous immunoglobulin (IVIg, ≥6 cycles), and 1 and ≥ 4 (but not 2-3) MG exacerbations in the first year after second-line therapy initiation. Any number of exacerbations were associated with high cost in a univariable analysis. A stratified cost analysis showed that patients with >1 exacerbation, ≥1 treatment switch, and high-dose steroid use in this first year experienced $198,487, $114,037, and $79,752 mean MG-related total healthcare spend during follow-up, respectively. These data suggest that patients receiving chronic IVIg or NSISTs for MG experience significant economic burden. Disease characteristics including exacerbation and treatment history may be an indicator of future high costs.

A Case for Synthetic Data in Regulatory Decision-Making in Europe.

Regulators are faced with many challenges surrounding health data usage, including privacy, fragmentation, validity, and generalizability, especially in the European Union, for which synthetic data may provide innovative solutions. Synthetic data, defined as data artificially generated rather than captured in the real world, are increasingly being used for healthcare research purposes as a proxy to real-world data (RWD). Currently, there are barriers particularly challenging in Europe, where sharing patient's data is strictly regulated, costly, and time-consuming, causing delays in evidence generation and regulatory approvals. Recent initiatives are encouraging the use of synthetic data in regulatory decision making and health technology assessment to overcome these challenges, but synthetic data have still to overcome realistic obstacles before their adoption by researchers and regulators in Europe. Thus, the emerging use of RWD and synthetic data by pharmaceutical and medical device industries calls regulatory bodies to provide a framework for proper evidence generation and informed regulatory decision making. As the provision of data becomes more ubiquitous in scientific research, so will innovations in artificial intelligence, machine learning, and generation of synthetic data, making the exploration and intricacies of this topic all the more important and timely. In this review, we discuss the potential merits and challenges of synthetic data in the context of decision making in the European regulatory environment. We explore the current uses of synthetic data and ongoing initiatives, the value of synthetic data for regulatory purposes, and realistic barriers to the adoption of synthetic data in healthcare.

Determinants of shingles vaccine acceptance in the United Kingdom.

BACKGROUND: The United Kingdom (UK) was the first European country to introduce a national immunisation program for shingles (2013-2014). That year, vaccination coverage ranged from 50 to 64% across the UK, but uptake has declined ever since. This study explored determinants of the acceptance of the shingles vaccine in the UK. METHODS: Vaccinated and unvaccinated individuals, who were eligible for the last catch-up cohort of the 2014-2015 shingles vaccination campaign, were identified using the Clinical Practice Research Datalink (the National Health Service data research service) and invited to participate by their general practitioner (GP). An anonymised self-administered questionnaire was developed using the Health Belief Model as a theoretical framework, to collect data on demographic and socio-economic characteristics, health status, knowledge, influences, experiences and attitudes to shingles and the shingles vaccine. Multivariable logistic regression was used to identify the factors associated with vaccination. Physicians' views concerning perceived barriers to vaccination were also assessed. RESULTS: Of the 2,530 questionnaires distributed, 536 were returned (21.2%) from 69 general practices throughout the UK. The majority of responders were female (58%), lived in care homes (56%) and had completed secondary or higher education (88%). There were no differences between vaccinated and unvaccinated responders. Being offered the shingles vaccine by a GP/nurse (odds ratio (OR) = 2.3), and self-efficacy (OR = 1.2) were associated with being vaccinated (p<0.05). In contrast, previous shingles history (OR = 0.4), perceived barriers to vaccination (OR = 0.7) and perceived control of the disease (OR = 0.7) were associated with not being vaccinated against shingles (p<0.05). Less than half (44.0%) of GPs were aware of the local communication campaigns regarding shingles and the shingles vaccine. CONCLUSIONS: Socio-psychological factors largely influence shingles vaccination acceptance in this study. The results add to existing evidence that healthcare providers (HCPs) have a pivotal role against vaccine hesitancy. Campaigns focusing on GPs and accessible information offered to eligible members of the public can further enhance shingles vaccine uptake.

Chemotherapy and targeted agents for colorectal cancer in a real-life setting anticipate guidelines: the COLCHIC cohort study.

Introduction of new agents for the treatment for colorectal cancer (CRC) has been accompanied by the publication of guidelines. The COLCHIC cohort was set up to evaluate CRC treatment practices and the use of these innovative and expensive agents. Patients initiating CRC treatment at the Bordeaux teaching hospital between 1 March 2005 and 1 March 2006 were identified, and treatment courses from 1 March 2005 to 31 December 2006 were studied; 192 patients were included, 188 with analysable data: 43 patients initiated 51 courses for non-metastatic cancer, 153 initiated 366 courses for metastatic cancer, eight patients initiated courses for both non-metastatic and metastatic cancer. Most treatments were used for indications found in guidelines published during the study (83.9%). Of the others, nearly half were approved in guidelines published subsequently. In this teaching hospital, prescribing practice was generally in line with recommendations, with an anticipation of future guidelines. This mostly concerned monoclonal antibodies, which were new at the time of the study.

The incidence of narcolepsy in Europe: before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns.

BACKGROUND: In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification. METHODS: We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom. RESULTS: Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time. CONCLUSIONS: The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.