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Background: Treatment targets for cardiovascular risk management (CVRM) make no distinction between women and men., Aim: To explore sex differences in achieving treatment targets in patients who participated in a nurse-led, integrated CVRM care programme in primary care between 2013 and 2019., Design & Setting: We conducted a dynamic cohort study in the Eindhoven region, which is the south-eastern part of the Netherlands., Method: We assessed outcomes of three biological risk factors (systolic blood pressure [SBP], low-density lipoprotein [LDL] cholesterol, and estimated glomerular filtration rate [eGFR]) and four lifestyle factors (smoking, physical activity, alcohol intake, and body mass index [BMI]). Points (1 = on target; 0 = not on target) were assigned for biological risk factors, lifestyle factors, and an overall score. Using the annual results, we applied multivariable regression models to study trends over time and differences in trends between women and men., Results: The number of participants increased from 24,889 to 38,067, mean age increased from 67.3 years to 71.5 years, with around 52 % women each year. The average of seven risk factors on target increased significantly from 4.6 to 4.9 in women, and from 4.7 to 5.0 in men, with no statistical difference between women and men. Differences between women and men in 2013 in the number of both biological and lifestyle factors on target did not materially change over time., Conclusion: Integrated cardiovascular management care led to improvements in cardiovascular risk factors on target, equally well in women than in men. Differences in risk factors on target between women and men in 2013 were still present in 2019., (Copyright © 2025, The Authors.)

Objectives: Symptoms of dizziness/lightheadedness are more often reported by females than males with an acute coronary syndrome (ACS). Therefore, we investigated if these symptoms are helpful for triage and diagnosis of ACS in females and males with acute chest discomfort., Design: Cross-sectional study., Setting: Nine out-of-hours service in primary care (OHS-PC) in the Netherlands participated, covering both rural and urban areas, serving a total population of 1.5 million people., Participants: 2195 patients were selected calling the OHS-PC with acute chest discomfort, 55.4% were females. Calls were selected based on International Classification of Primary Care codes and keywords, that is, chest pain, heart complaints, heart, myocardial infarction, heart attack, heart infarction or common abbreviations of these keywords. Recordings were excluded if (1) they were of poor quality, (2) the conversation was not a triage conversation, (3) patients were <18 years, (4) patients did not live in the vicinity of the OHS-PC, and (4) general practitioners did not want to provide follow-up information including the final diagnosis., Primary and Secondary Outcome Measures: The prevalence of dizziness/lightheadedness among patients calling the OHS-PC with acute chest discomfort and the relation between dizziness/lightheadedness and (1) urgency allocation and (2) a final diagnosis of ACS., Results: Among 2195 patients who called the OHS-PC with acute chest discomfort, 251 (11.4%) had an ACS (8.3% females, 15.3% males). Females more often reported concurrent dizziness/lightheadedness than males (14.7% vs 10.9%, p=0.008). However, this was not observed in those with confirmed ACS (9.9% of the females vs 9.3% of the males, p=0.881). Reporting of dizziness/lightheadedness was not positively related to an ACS diagnosis in females (OR 0.61 (95% CI 0.31 to 1.21)) or in males (OR 0.82 (95% CI 0.45 to 1.47)). In contrast, both females and males with concurrent dizziness/lightheadedness more often received a high urgency allocation than those without these symptoms., Conclusions: Dizziness/lightheadedness are common symptoms but are not positively related to an ACS diagnosis in both females and males with acute chest discomfort. It seems not worthwhile to give females and males with acute chest discomfort and concurrent dizziness/lightheadedness a higher urgency allocation than those without these symptoms., Trial Registration Number: NTR7331., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Despite programmatic protocolised care and structured support, considerable variation is observed in completeness of registration and achieving targets of cardiovascular risk management (CVRM) between individual GPs in the Netherlands., Aim: To determine whether completeness of registration and achieved targets of cardiovascular risk factors improves with practice visitation., Design & Setting: Observational study utilising the care group's database (2016-2019), comparing changes in registration and achieved targets in non-visited practices and visited practices., Method: We compared completeness scores of registration and scores of targets achieved before visitation and 1 year after visitation. Data were analysed on patient level and GP level. Separate analyses were performed among GPs who were ranked in the lower 25% of score distributions., Results: We observed no clinically relevant improvements in completeness of registration and targets achieved in 2017, 2018, and 2019 that could be attributed to visitations in the previous year, both on individual patient level and on aggregated level per general practice. In practices ranked in the lower 25% of the distribution, improvements over time were clinically relevant and larger than the overall changes. Yet, these findings were irrespective of the number of practice visitations., Conclusion: Practice visitations in our setting did not seem to lead to improvements in practice performance, nor in completeness of registration of risk factors or in reaching predefined target goals for cardiovascular risk factors., (Copyright © 2024, The Authors.)

Introduction: In patients suspected of stroke or transient ischemic attack (TIA), rapid triaging is imperative to improve clinical outcomes. For this purpose, balance-eye-face-arm-speech-time (BEFAST) items are used in out-of-hours primary care (OHS-PC). We explored the risk of stroke and TIA among BEFAST positive patients calling to the OHS-PC, and assessed whether additional predictors could improve risk stratification., Methods: This is a cross-sectional study of retrospectively gathered routine care data from telephone triage tape-recordings of patients calling the OHS-PC with neurological deficit symptoms, classified as BEFAST positive. Four models-with the predictors age, sex, a history of cardiovascular or cerebrovascular disease, and cardiovascular risk factors-were fitted using logistic regression to predict the outcome stroke or TIA. Likelihood ratio testing was used to select the best model, which was subsequently internally validated., Results: The risk of stroke or TIA diagnosis was 52% among 1,289 BEFAST positive patients, median age 72 years, 56% female sex. Of patients with the outcome stroke/TIA, 24% received a low urgency allocation, while 92% had signs or symptoms when calling. Only the addition of age and sex improved predicting stroke or TIA (internally validated c-statistic 0.72, 95%CI 0.69-0.75). The predicted risk of stroke or TIA remained below 20% in those aged below 40. Females aged 70 or over and males aged 55 or over, had a predicted risk above 50%., Discussion: Urgency allocation appears to be suboptimal in BEFAST positive patients calling the OHS-PC. Risk stratification could be improved in this setting by adding age and sex., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 van Royen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clinical prediction models provide risks of health outcomes that can inform patients and support medical decisions. However, most models never make it to actual implementation in practice. A commonly heard reason for this lack of implementation is that prediction models are often not externally validated. While we generally encourage external validation, we argue that an external validation is often neither sufficient nor required as an essential step before implementation. As such, any available external validation should not be perceived as a license for model implementation. We clarify this argument by discussing 3 common misconceptions about external validation. We argue that there is not one type of recommended validation design, not always a necessity for external validation, and sometimes a need for multiple external validations. The insights from this paper can help readers to consider, design, interpret, and appreciate external validation studies., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: A subset of patients with superficial venous thrombosis (SVT) experiences clot propagation towards deep venous thrombosis (DVT) and/or pulmonary embolism (PE). The aim of this systematic review is to identify all clinically relevant cross-sectional and prognostic factors for predicting thrombotic complications in patients with SVT., Design: Systematic review., Data Sources: PubMed/MEDLINE and Embase were systematically searched until 3 March 2023., Eligibility Criteria: Original research studies with patients with SVT, DVT and/or PE as the outcome and presenting cross-sectional or prognostic predictive factors., Data Extraction and Synthesis of Results: The CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling (CHARMS) checklist for prognostic factor studies was used for systematic extraction of study characteristics. Per identified predictive factor, relevant estimates of univariable and multivariable predictor-outcome associations were extracted, such as ORs and HRs. Estimates of association for the most frequently reported predictors were summarised in forest plots, and meta-analyses with heterogeneity were presented. The Quality in Prognosis Studies (QUIPS) tool was used for risk of bias assessment and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) for assessing the certainty of evidence., Results: Twenty-two studies were included (n=10 111 patients). The most reported predictive factors were high age, male sex, history of venous thromboembolism (VTE), absence of varicose veins and cancer. Pooled effect estimates were heterogenous and ranged from OR 3.12 (95% CI 1.75 to 5.59) for the cross-sectional predictor cancer to OR 0.92 (95% CI 0.56 to 1.53) for the prognostic predictor high age. The level of evidence was rated very low to low. Most studies were scored high or moderate risk of bias., Conclusions: Although the pooled estimates of the predictors high age, male sex, history of VTE, cancer and absence of varicose veins showed predictive potential in isolation, variability in study designs, lack of multivariable adjustment and high risk of bias prevent firm conclusions. High-quality, multivariable studies are necessary to be able to identify individual SVT risk profiles., Prospero Registration Number: CRD42021262819., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Since 2010, an increasing number of patients have participated in a nurse-led integrated cardiovascular risk management programme in the Netherlands. Because it is important to understand which patients discontinue and why, when evaluating the effectiveness of the care programme, the aim was to identify the reasons for discontinuation., Methods: Electronic health records of 3997 patients enrolled in a nurse-led integrated cardiovascular risk management programme that started on April 1 st, 2010, were manually scrutinized for reasons for discontinuation between April 1 st, 2010, and April 1 st, 2018. In addition to death and moving to a diabetes care programme, we describe 7 different reasons why patients discontinued the programme and compared the patient characteristics of those who discontinued the programme without specific reasons with those who remained in the care programme for 8 years., Results: Between April 1 st, 2010, and April 1 st, 2018, 1,190 participants (29.8%) discontinued the CVRM care programme, of whom 271 participants died (6.8%) and 195 were transferred to a diabetes care programme (4.9%). The remaining 724 patients (18.1%) participated 5 years before discontinuation. Of these, 67 (9.3%) had a previous cardiovascular event at the start of the programme. In 355 patients, a specific reason for discontinuation was not found. At baseline, these patients less frequently had a history of CVD than those who continued the programme for 8 years (1.7 vs. 22.6%), were younger (62 vs. 67 years), had less registered cardiovascular comorbidity (atrial fibrillation: 1.1 vs. 7.2%; congestive heart failure 0.3 vs. 1.2%; chronic kidney disease 0.0 vs. 4.5%), were more often smokers (13.0% vs. 4.3%) and took blood pressure- and lipid-lowering drugs twice as often., Conclusions: In our study we observed that participants who discontinued the nurse-led integrated CVRM care programme between 2010 and 2018 without specific reason or on request were younger, without previous CVD, had less cardiovascular comorbidity and were better adjusted to medication. Exploring the patients' reasons for discontinuation can contribute to an individualized approach to prevent or reduce discontinuation., (© 2024. The Author(s).)

Objective: To investigate whether frail elderly people with atrial fibrillation (AF) who are currently using a vitamin K antagonist (VKA) should be switched to a direct-acting oral anticoagulant (DOAC)., Design: Randomized clinical trial., Methods: 662 frail elderly AF patients were switched to a DOAC, and 661 patients continued their VKA. The primary endpoint was a major or clinically relevant non-major bleeding during 1 year of follow-up. Secondary endpoints included thrombo-embolic events., Results: The mean age of the included patients was 83 years. In the 'switch to DOAC arm', 101 bleeding events (15.3%) occurred and in the 'continue with VKA arm', 62 bleeding events (9.4%); an increase of 69% more bleeding events (P-value 0.001). The number of thrombo-embolic events was not significantly different between both groups., Conclusion: Switching from a VKA to a DOAC in frail elderly people with AF leads to 69% more bleeding, without a difference in thrombo-embolic events.

Background: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC)., Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min -1 ·1.73 m -2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events., Results: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61)., Conclusions: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications., Registration: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study)., Competing Interests: Disclosures Dr Hemels reports payment for educational lectures from Bayer, BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. Dr Huisman reports payment to institution from Dutch Healthcare Fund, Dutch Heart Foundation, Bayer Health Care, Pfizer, and Leo Pharma. Dr Kruip reports payment to institution of unrestricted grants from Sobi, payment to institution of research grants from The Netherlands Organisation for Health Research and Development and The Netherlands Thrombosis Foundation, and payment to institution of speaker fees from Sobi, Roche, Dr Geersing reports payment to institution of unrestricted grants from Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer, and Daiichi Sankyo. Dr Rutten reports payment to institution of unrestricted grants from Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer, and Daiichi Sankyo.

Introduction: Integrated care is effective in reducing all-cause mortality in patients with atrial fibrillation (AF) in primary care, though time and resource intensive. The aim of the current study was to assess whether integrated care should be directed at all AF patients equally., Methods: The ALL-IN trial (n = 1,240 patients, median age 77 years) was a cluster-randomized trial in which primary care practices were randomized to provide integrated care or usual care to AF patients aged 65 years and older. Integrated care comprised of (i) anticoagulation monitoring, (ii) quarterly checkups and (iii) easy-access consultation with cardiologists. For the current analysis, cox proportional hazard analysis with all clinical variables from the CHA2DS2-VASc score was used to predict all-cause mortality in the ALL-IN trial. Subsequently, the hazard ratio and absolute risk reduction were plotted as a function of this predicted mortality risk to explore treatment heterogeneity., Results: Under usual care, after a median of 2 years follow-up the absolute risk of all-cause mortality in the highest-risk quarter was 31.0%, compared to 4.6% in the lowest-risk quarter. On the relative scale, there was no evidence of treatment heterogeneity (p for interaction = 0.90). However, there was substantial treatment heterogeneity on the absolute scale: risk reduction in the lowest risk- quarter of risk 3.3% (95% CI -0.4% - 7.0) compared to 12.0% (95% CI 2.7% - 22.0) in the highest risk quarter., Conclusion: While the relative degree of benefit from integrated AF care is similar in all patients, patients with a high all-cause mortality risk have a greater benefit on an absolute scale and should therefore be prioritized when implementing integrated care., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: G.J. Geersing, F.H. Rutten, and M.E.W. Hemels report unrestricted institutional grants for performing research in the field of atrial fibrillation from Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer and Daiichi Sankyo. I.C. van Gelder reports consultancy fees from Boston, BMS and Bayer to the institution, unrestricted research grants from the Netherlands Cardiovascular Research Initiative, unrestricted research grant from the European Union’s Horizon 2020 research and innovation programme under grant agreement: EHRA-PATHS (945260). M. Rienstra reports Consultancy fees from Bayer, Microport, InCarda Therapeutics to the institution, an unrestricted research grant from ZonMW and the Dutch Heart Foundation; DECISION project 848090001, unrestricted research grants from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation; RACE V (CVON 2014–9), RED-CVD (CVON2017-11), an unrestricted research grant from Top Sector Life Sciences & Health to the Dutch Heart Foundation (PPP Allowance; CVON-AI (2018B017)), and an unrestricted research grant from the European Union’s Horizon 2020 research and innovation programme under grant agreement; EHRA-PATHS (945260). S. van Doorn reports an unrestricted institutional grant for performing research in the field of stroke diagnosis from Stoffels-Hornstra. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Trinks-Roerdink et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)