There are inequalities and obstacles in treatment of cardiovascular (CV) diseases that impact patient clinical outcomes, especially in the management of hypercholesterolemia and atrial fibrillation. This is what emerges from the data of the sub-analyses of the SANTORINI observational study and the ETNA-AF study program, presented by Daiichi Sankyo at the 2024 Congress of the European Society of Cardiology (ESC), to reaffirm its commitment to supporting better cardiovascular care for patients, through holistic approaches for the treatment of these diseases.
Gender inequalities in CVD treatment and LDL-C target achievement
The increase in low-density lipoprotein cholesterol (C-LDL) is a key modifiable risk factor for major cardiovascular events. It has been shown that for every ~39 mg/dL reduction in LDL-C, there is a 22% reduction in major cardiovascular events at 1 year. [vii],[viii] According to data from the SANTORINI observational study, in Europe women with high or very high CV risk were undertreated and achieved lower levels of C-LDL recommended by the guidelines.1
As part of its commitment to expanding medical knowledge to help protect people from cardiovascular disease, Daiichi Sankyo designs and funds studies such as SANTORINI, investigating the causes of the burden of cardiovascular disease in Europe. A new sub-analysis of the SANTORINI study, conducted on 5,197 male patients, with a mean age of 65 years, and 2,013 female patients, with a mean age of 66 years, showed that female patients were undertreated compared with male patients, and fewer of them achieved guideline-recommended LDL-C levels within the study. 1
“We know that the burden of cardiovascular disease for women is equal to that of men and that patients of both sexes remain undertreated. [ix],[x]But this new sub-analysis of the SANTORINI study further suggests that, in clinical practice, women overall are disproportionately undertreated and do not always achieve LDL-C goals. “recommended”, prof. declared. David NanchenUniversity of Lausanne, Centre for Primary Care and Public Health (Unisanté), “These findings underscore the need for more widespread attention to better manage cardiovascular disease risk in women.”
The impact of treatment non-adherence on patient outcomes
The effectiveness of oral anticoagulation treatment of atrial fibrillation relies on adherence and persistence. Non-adherence to single non-vitamin K antagonist oral anticoagulants (NOACs) has been associated with an increased risk of stroke in patients with atrial fibrillation (AF). 2
Results of a new post hoc sub-analysis of the ETNA-AF program showed that of the 9,417 patients [13.164 arruolati] (71.5%) who completed the 4-year study, 87.4% remained on edoxaban. 3 Discontinuation and non-persistence on treatment were both associated with factors such as increasing age, male gender, extremes of body weight, low renal function, heart failure, vascular disease, chronic liver disease, alcohol use, perceived frailty, chronic obstructive pulmonary disease, smoking, current AF symptoms, and ablation. 3
“The high number of patients who continued treatment with edoxaban throughout the duration of the four-year study, this is good news for our efforts to mitigate therapeutic non-adherence”2commented Prof. Raffaele De Caterina, MD, PhD, FESC, Director of Cardiology at the University Hospital of Pisa. “We hope that the factors associated with non-persistence observed in the study may also help in the development of therapeutic strategies in clinical practice, benefiting patient outcomes.”
Treatment of patients with frailty and comorbidities
Barriers such as complex multimorbidity, which prevent recommending anticoagulation for the management of nonvalvular atrial fibrillation (NVAF), are significant in frail patients. [xii] For this reason, the prescription of NOACs in the frail patient population is less than 50%.12 Physicians must balance the risk of stroke and the risk of bleeding when making prescribing decisions. 12
In In a separate sub-analysis of the data, patients were divided into low, medium and high tertiles based on body mass index. (BMI), body surface area (BSA), and lean mass. Rates of thromboembolic events were low (0.7-0.9%/100/subjects/year) and similar across tertiles. However, higher rates of bleeding events were observed in the lower tertiles ([2,2-2,4%]) compared to the average ones ([1,5-1,8%]) and high ([1,4-1,5%]) for ASC and lean mass. This suggests that these variables should be considered more than BMI in the analysis of outcomes in patients treated with edoxaban. 4,6
At Daiichi Sankyo we continue to to deliver on our long-term commitment to provide scientific evidence that can support the optimal treatment of patients with cardiovascular disease and to find solutions for individuals who have been under-treated”, Dr. said. Stefan Seyfried, Vice President of Medical Affairs, Specialty Medicines, Daiichi Sankyo Europe. “Our promise to patients is to continue to shine a light on inequities and unmet needs in cardiovascular care, with the goal of reducing the burden on patients and their caregivers.”
The SANTORINI studio
The SANTORINI study is a multinational, prospective, observational, non-interventional study that enrolled 9,602 patients at high and very high cardiovascular risk at 623 sites in 14 European countries, between March 2020 and February 2021.10 The primary objective was to document, in real clinical practice, over a 1-year follow-up, current therapeutic approaches to reducing LDL-C in subjects belonging to the highest cardiovascular risk categories (high and very high risk) who required lipid-lowering treatment.10The study included both previously diagnosed and treated patients and newly diagnosed patients who required treatment.10
Complete baseline data were included on 9,044 patients (mean age: 65.3 ± 10.9 years; 72.6% male).10
Physicians used the ESC/EAS 2019 guidelines as the basis for CV risk classification in 52% of patients; 29.2% of patients were classified as high risk and 70.8% as very high risk.10 After central reassessment using the same guidelines, 6.5% of patients were classified as high risk, and 91% were classified as very high risk.10 Overall, 21.8% of patients had no documented lipid-lowering therapies, 54.2% were receiving monotherapy, and 24% were receiving a combination of lipid-lowering therapies.10 The median LDL-C was 81 mg/dL, LDL-C according to the respective ESC/EAS 2019 guidelines risk class.10
References
[i] Nanchen, D., et al. Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study. Oral presentation, ESC Congress 30 August 2024.
[ii] Vitolo, M., et al. The importance of adherence and persistence with oral anticoagulation treatment in patients with atrial fibrillation. European Heart Journal – Cardiovascular Pharmacotherapy. 2021. 7;(FI1): f81–f83
[vi] Boriani, G., et al. Impact of body weight and body mass index on clinical outcomes of edoxaban therapy in atrial fibrillation patients included in the ETNA-AF-Global registry. ESC 2024
[vii] Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010. 376(9753): 1670–1681
[viii] NHS England. Improving lipid management to reduce cardiovascular disease and save lives. Available at: https://www.england.nhs.uk/long-read/improving-lipid-management-to-reduce-cardiovascular-disease-and-save-lives/#:~:text=Raised%20LDL%20cholesterol%20is%20one,vascular%20events%20after%201%20year. Last accessed August 2024.
[ix] ESC. Cardiovascular Disease in Women. Available at: https://www.escardio.org/The-ESC/Advocacy/women-and-cardiovascular-disease. Last accessed August 2024.
[x] Ray, K.K., et al. Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study. Lancet. 2023. 29: 100624.
[xi] Daiichi Sankyo Europe – About ENTA-AF (UK). Available at: https://www.daiichi-sankyo.eu/media/about-etna-af-uk/. Last accessed August 2024.
[xii] Bul, M., et al. Frailty and oral anticoagulant prescription in adults with atrial fibrillation: A systematic review. Aging Medicine. 2022. 6(2): 195–206
[xiii] Edoxaban Treatment in Routine Clinical Practice for Patients With Non Valvular Atrial Fibrillation (ETNA-AF-EU). Available at: https://clinicaltrials.gov/ct2/show/NCT02944019. Last accessed August 2024.
[xiv] Edoxaban Treatment in Routine Clinical Practice for Patients With Atrial Fibrillation in Korea and Taiwan (ETNA-AF-KOR-TWN). Available at: https://clinicaltrials.gov/ct2/show/NCT02951039. Last accessed August 2024.
[xv] Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF-Hong Kong). Available at: https://clinicaltrials.gov/ct2/show/NCT03247582. Last accessed August 2024.
[xvi] Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (NVAF). Available at: https://clinicaltrials.gov/ct2/show/NCT03247569. Last accessed August 2024.
[xvii] ETNA-AF-Japan. Available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000019728. Last accessed August 2024.
