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Health care delivery, economics and global health care
Original research
Sex differences in early-onset atrial fibrillation in Norwegian primary care: a retrospective national database analysis
  1. Silje Madeleine Kalstø1,
  2. Ståle Nygård2,
  3. Inger Ariansen3,
  4. Arnljot Tveit1,4 and
  5. Ingrid Elisabeth Christophersen1,5
  1. 1Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway
  2. 2Center for Bioinformatics, University of Oslo, Oslo, Norway
  3. 3Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway
  4. 4Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  5. 5Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
  1. Correspondence to Dr Ingrid Elisabeth Christophersen; uxchia{at}vestreviken.no

Abstract

Background Individual variation in the need for healthcare constitutes knowledge gaps for young atrial fibrillation (AF) patients. We aimed to estimate the prevalence and primary care burden of early-onset AF in Norway, emphasising sex differences, in a nationwide healthcare database.

Methods We used data from the Norwegian Control and Payment of Health Reimbursement database to identify all Norwegian residents ≥18 years of age registered with a primary care physician (PCP) in 2019, with onset of AF at ≤50 years of age (early-onset AF) in the period 2006–2019. From the accumulated number of early-onset AF cases among current residents, we calculated the prevalence in 2019. The group-level primary care burden was calculated as the total number of annual AF consultations divided by the annual number of AF patients (2014–2018), and individual burden as the mean number of consultations per AF patient per year within the study period. We analysed the distribution of AF consultations between PCP and primary care emergency room (ER) services in total and by sex.

Results We identified 10 925 Norwegian residents with early-onset AF in 2019 (26.3% women, mean age 48.4 years). The prevalence of early-onset AF was 0.34% (women: 0.19%, men: 0.50%). The early-onset AF population had on average one annual primary care consultation for AF. The individual burden of annual AF consultations varied widely; <1: 66% of women and 54% of men, (1–5]: 25% of women and 36% of men, (5–10]: 6% of women and 8% of men, ≥10: 2% of women and 2% of men. A higher proportion of men (71%) than women (38%) attended both PCP and ER services due to AF.

Conclusions The study confirmed a low prevalence of early-onset AF, with substantial sex differences and individual variation in primary healthcare needs. Our results signal a need for a higher resolution with regard to age groups in future research on burden and sex differences in early-onset AF.

  • PRIMARY CARE
  • Atrial Fibrillation
  • Epidemiology
  • Delivery of Health Care
  • Global Burden of Disease

Data availability statement

Data may be obtained from a third party and are not publicly available. The data underlying this manuscript cannot be shared according to guidelines on receipt of KUHR datasets.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/openhrt-2024-002695

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    WHAT IS ALREADY KNOWN ON THIS TOPIC

    • Atrial fibrillation (AF) constitutes a major societal and individual health burden worldwide, yet the burden of early-onset AF is less studied.

    • AF in young patients, especially from a primary care point of view, constitutes knowledge gaps, as registry studies of AF primarily have reported data from hospital registries in older individuals.

    • Numerous studies have investigated sex differences for AF, but whether previously studied differences are generalisable to early-onset AF is unknown.

    WHAT THIS STUDY ADDS

    • The study provides nationwide register-based data on the prevalence and primary care burden of early-onset AF.

    • We revealed substantial sex differences and individual variation in healthcare needs for young AF patients treated in primary care.

    • The findings may raise some thoughts around whether young women with AF are undertreated in primary care or actually represent a less burdened group compared with young men.

    HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

    • Our results signal a need for a higher resolution with regard to age groups in future research on burden and sex differences in early-onset AF.

    • The individual variation and sex differences in early-onset AF demonstrated in our results, underline the need for attention to patient-specific needs in primary care treatment of AF.

    Introduction

    Atrial fibrillation (AF) is by far the most common cardiac arrhythmia, and, with a lifetime risk of 37% for people over the age of 55 years,1 it contributes to both individual and societal health burden.2 The prevalence of AF was recently reported to be 3.4% in Norway with a population of 5.4 million.3 Prevalence studies based on healthcare coding practice have primarily been carried out on hospital data and are limited to inpatient or outpatient hospital treatment of AF.3–5 However, a few studies have reported AF prevalence in the primary care sector,6–10 although not age stratified, and primarily with attention to cardiovascular complications secondary to AF. Female sex is a contributing risk factor for stroke and is associated with more serious complications and higher mortality in AF patients.10 11 Men and women report different symptoms of AF, and several studies have found that women are less likely to have asymptomatic AF than men and that women report more frequent and severe symptoms.12 13 Women also consistently report lower quality of life (QoL) than men, both in AF and in the general population, with some evidence suggesting that women’s QoL is more affected by AF than is the case in men.14 15 Moreover, women are more frequently diagnosed with depression alongside AF compared with men.12

    AF in younger patients is less investigated, and although sex differences in AF have been shown through various studies, the generalisability to early-onset AF is uncertain. In Norway, Sharashova et al recently reported differences in risk factors for AF between women and men in a relatively young AF cohort, in which the most prevalent risk factor for developing AF was overweight in men and hypertension in women.16 Pathological mechanisms contributing to early-onset AF may differ between sex and age groups and might affect the disease burden and healthcare needs due to AF.

    The term burden is used with various meanings in relation to AF. Primary care registry data can be used to describe disease burden, defined as the frequency, duration, and severity of AF episodes, and the clinical burden of how symptoms, treatment, or complications of AF, affect QoL and costsc.17 Murphy et al reported the primary care burden of AF in Scotland from 2001 to 2002 and found that individuals with AF had on average one annual contact with primary care.8 Murphy et al also reported a higher rate of consultations due to AF for men compared with women in all age groups,8 in contrast to studies that have suggested that women are more likely to seek care for their symptoms.12 13 18 Individual variation and sex differences in the need for healthcare services constitute knowledge gaps for young AF patients in primary care. Here, we present sex-specific data on the prevalence of AF and primary care burden in a nationwide early-onset AF population with 13 years of observation time.

    Methods

    The Norwegian Control and Payment of Health Reimbursement database

    In Norway, with a population of 5.4 million, healthcare is publicly financed, and all residents are entitled to a primary care physician (PCP), with a coverage of 98.6% in 2019.19 PCPs have both scheduled medical consultations and, to some extent, urgent patient referrals during ordinary working hours. In addition, the primary care service provides 24-hour emergency room (ER) medical service for acute illness occurring when the PCP is not available. For each consultation within primary care, the PCP and ER physicians send a claim to the Norwegian Directorate of Health. Each claim must contain at least one International Classification of Primary Care second edition (ICPC-2)-diagnosis code, which is registered in the Norwegian Control and Payment of Health Reimbursement (KUHR) database. KUHR also contains information on the basis of reimbursement, administrative and procedure codes, type of contacts (no contact, simple contact, phone contact, consultation and home visit), and whether a PCP or an ER physician was responsible for the contact.20 Reimbursement claims have been recorded in the KUHR database since 2006.

    Statistics Norway

    Statistics Norway is the national statistical institute of Norway, responsible for official statistics and analyses. We obtained population figures on 1 January 2019, in total and by sex, based on the National Population Registry.21 Statistics Norway provides aggregated tables of the annual consultation rate within primary care, due to all available diagnosis codes in the Norwegian population. The Statistics Norway data for all-cause consultation rate within the primary care is based on data from KUHR and was available from 2014. We, therefore, obtained available reference data, by sex and age, between the years 2014 and 2018.22 23

    Study population for calculation of prevalence

    A dataset was extracted from KUHR on 13 November 2019, consisting of all individuals aged ≥18 years registered with ≥1 diagnosis code of K78 (AF or flutter), before the age of 50 years, from 2006 to 2019. From 2006, the dataset allowed an increase in age up to 62 years of age in 2019 (online supplemental figure 1). Individuals with an invalid social security number (≠11 digits and/or first two digits ≥32) and individuals who were not registered with a PCP in 2019 were excluded (online supplemental figure 5, online supplemental table 7). We defined prevalent early-onset AF as any registered diagnosis code of AF as the primary or secondary diagnosis in the KUHR database before age 50 years (figure 1). We calculated the prevalence by dividing the number of individuals with early-onset AF by the total Norwegian population of 2019 from Statistics Norway. Subgroup analyses were performed as a total, by sex and by age strata: 18–29, 30–39, 40–49 and 50–62.24 In the sensitivity analysis, we included individuals with ≥2 diagnosis codes of K78 (online supplemental table 1).

    Figure 1
    Figure 1

    Study population. Flow chart for the identification of the study population. AF, atrial fibrillation; ER, emergency room; KUHR, Norwegian Control and Payment of Health Reimbursement; PCP, primary care physician.

    Study population for calculation of burden

    In the analyses of early-onset AF burden, we included early-onset AF cases registered with ≥1 consultation with AF as the primary diagnosis in KUHR (figure 1).

    Group-level burden of early-onset AF on the primary care system

    To evaluate the burden of early-onset AF at a population level, we included all individuals entering KUHR before the end of 2018 as the last full year of the dataset. Comparable aggregated Statistics Norway tables of annual all-cause consultation rates within the Norwegian population were available from 2014, across sex and age strata (20–29, 30–49 and 50–66).22 We calculated a 5-year mean population-level burden of early-onset AF, from the mean number of AF-related contacts with a PCP or a primary care ER physician per individual per separate year from 2014 to the end of 2018. For sensitivity analyses, we excluded consultations related to the female reproductive system from the calculation of the annual contact rate due to all-cause consultations (online supplemental table 2).

    Individual burden of early-onset AF

    To assess individual burden, we calculated the number of primary care consultations per individual per year, from the first registered AF diagnosis code in KUHR, until the end of the study. We excluded individuals who had less than 1 year of follow-up, that is, the first AF diagnosis registered less than 1 year before the end of the study (13 November 2018–13 November 2019). We calculated the mean number of AF consultations per year, per individual and by sex and divided the results into subclasses of individual AF burden; <1 annual consultation, (1–5] annual consultations, (5–10] annual consultations and ≥10 annual consultations. The individual burden was calculated separately for PCP and ER services.

    Distribution of consultations across PCP and ER services

    We compared the distribution of AF consultations across PCP and primary care ER services, to identify any differences between AF consultations within ordinary working hours (PCP) and the need for urgent medical assistance due to AF (ER), in total and by sex. We performed a subgroup analysis in individuals with new-onset AF. New-onset AF was defined as ≥1 AF diagnosis code registered in KUHR within the last year of the study period (13 November 2018–13 November 2019) and not before that.

    Comorbidity

    To evaluate differences in comorbidity between women and men, we assessed sex differences in comorbidity based on all consultations during the whole study period. We identified the most prevalent diagnosis codes registered in combination with an AF diagnosis code.

    Statistical methods

    We tested for differences in individual burden between women and men, using the Poisson test. Sex differences in comorbidity were tested using Fisher’s exact test. For the testing of individual hypotheses, a p<0.05 was used as the significance threshold. For multiple testing (eg, sex differences in multiple secondary diagnoses), the Benjamini-Hochberg procedure for calculating false discovery rate (FDR) was applied, and FDR<0.1 was used as a significance criterion.25

    We calculated the prevalence of early-onset AF from the accumulated number of early-onset AF cases from 1 January 2006 to 13 November 2019, among current residents, and as a proportion of the Norwegian population figures for 2019 from Statistics Norway.24 Analyses were performed by using R V.3.4.4.26

    Results

    Study population

    We initially identified 12 211 potential individuals with early-onset AF in KUHR (figure 1) of which 10.5% were excluded due to an invalid social security number or no registered PCP in 2019 (online supplemental figures 4–6, online supplemental tables 7 and 8). Invalid social security number due to missing data in the database or patients with a non-Norwegian ID constituted 2.5%. Individuals not registered with a PCP in 2019 (possibly emigrated or died between 2006 and November 2019) constituted 8%. Our study population for calculation of prevalence then consisted of 10 925 Norwegian residents with early-onset AF (26% women, mean age 48.4 years). For analyses of burden, we excluded 794 individuals who did not receive an AF diagnosis at a consultation, and 450 individuals who only received the AF diagnosis as a secondary diagnosis. The baseline study population for the calculations of primary care burden included 9681 individuals (25% women, mean age 48.7 years).

    Prevalence of early-onset AF in the Norwegian population

    In 2019, the prevalence of early-onset AF in individuals aged 18–62 years was 0.34%, with a men:women ratio of 2.8. The youngest age group of 18–29 years had a prevalence of 0.05%, with a men:women ratio of 1.8. For the age group 30–39 years, 40–49 years and 50–62 years, the prevalence was 0.19%, 0.50% and 0.62%, respectively, with an increasing men:women ratio with age (table 1, figure 2A). The sensitivity analyses, excluding all individuals with only one AF diagnosis code registered in KUHR, reduced the overall prevalence of early-onset AF to 0.25%. The youngest age group (18–29 years) was most affected in the sensitivity analysis, and the decrease in prevalence was most pronounced for women across all age groups (online supplemental table 1).

    View this table:
    Table 1

    Prevalence of early-onset AF

    Figure 2
    Figure 2

    Sex differences in early-onset AF prevalence and burden. (A) Prevalence of early-onset AF in Norway in 2019, per 100 individuals in strata of age and sex. (B) Sex differences in group-level burden as the mean number of primary care consultations per year, in total, by sex and by age group. The first row of columns represents consultations due to AF within the early-onset AF population. The second row of columns represents consultations due to all-cause of contact in the general Norwegian population. (C) Individual burden of early-onset AF by sex and burden, assessed as the number of consultations with a PCP due to AF. Y-axis: Number of consultations per individual per year being diagnosed with early-onset AF, with individual disease burden grouped as low (green), Intermediate (yellow), high (orange) and heavy (red). X-axis: Proportion of individuals belonging to each category. (D) The distribution of contact points for consultations by sex, within the early-onset AF population in primary care (%), for the total study population and for individuals with new-onset of AF within the last year of the study period. AF, atrial fibrillation; ER, emergency room; PCP, primary care physician.

    Primary care burden of early-onset AF

    Group-level burden

    Between the years 2014 and 2018, the mean annual number of individuals with early-onset AF was 9609 (26% women, age 20–61 years). Divided into age strata, the corresponding numbers were 544 (33.3% women) in the youngest age group 20–29 years, 5085 (27.1% women) in the age group 30–49 years and 3980 in the age group ≥50 years. The maximum age increased from 57 years in 2014, to 61 years in 2018 due to the increased observational time (online supplemental figure 1). The early-onset AF population had on average one annual primary care consultation due to AF (table 2, figure 2B). The mean annual number of consultations due to AF increased with age. For all ages within the AF population, men had a higher consultation rate than women, with a men:women ratio of 1.24. In the general population, men had a lower consultation rate than women, with a men:women ratio of 0.62, and the mean annual primary care consultation rate ranged from 2.5 to 3.4, increasing with age.

    View this table:
    Table 2

    Mean number of primary care consultations per patient per year

    Individual burden

    The mean number of PCP consultations per individual per year was 1.80 (women 1.57, men 1.87) consultations. A significantly higher proportion of women had a low individual AF burden compared with men (women 66.3%, men 53.9%) with <1 annual consultation, whereas a significantly higher proportion of men (women 25.1%; men 36.4%) had 1–5 annual consultations. Only 7.2% (women 6.3%; men 7.5%) of the individuals registered with early-onset AF had a high disease burden of 5–10 annual consultations and a small subset (2.2%; women 2.3%, men 2.1%) displayed a heavy disease burden of >10 annual consultations (figure 2C, online supplemental table 3). The mean number of individual ER consultations per year was 0.36 (women: 0.34, men: 0.36), in which over 95% of the patients with early-onset AF who used the primary care ER had <1 annual consultation (online supplemental table 4).

    Sex differences in distribution of consultation across PCP and ER services

    Between 2006 and 2019, 9681 individuals (24.9% women) with early-onset AF were registered with one or more consultations, and in the aggregate, they underwent 118 231 consultations due to AF (men:women 3.9). The majority (93.6%) of consultations were with a PCP, whereas only 6.4% were ER consultations. A total of 8357 (86.3%) individuals had at least one consultation with a PCP, whereas 4077 (42.1%) had at least one ER consultation. Nearly one-third (2753; 28.4%) of the patients had contacts with both services, whereas 5604 (57.9%) consulted a PCP only, and 1324 (13.7%) consulted the ER only. New-onset AF was identified in 328 (25.9% women) individuals in KUHR during the last year of the study period. When assessing the number of consultations with PCPs and the primary care ER service separately for the new-onset AF patients, we found that 37.6% of the women and 71.2% of the men had consulted both their PCP and the primary care ER due to AF. One-third had only seen their PCP (47.1% of the women and 25.5% of the men), whereas only 6.4% (15.3% of the women and 3.3% of the men) had only been in contact with the primary care ER (figure 2D).

    Comorbidity

    Of all contacts registered as an ordinary consultation with AF as the primary diagnosis code, 82% were registered with an isolated AF diagnosis, whereas the remaining 18% (women 21 %, men 17%) had a secondary diagnosis registered (online supplemental figures 2–4). The most common secondary diagnoses were uncomplicated hypertension (women 1.08%; men 1.98%) and non-insulin-dependent diabetes (women 1.10% and men 1.59%). Both diagnoses were more prevalent in men. Women were more often diagnosed with valvular heart disease, thyroid-related conditions, as well as depression, anxiety and muscle pain. Men had a significantly higher prevalence of lipid disorders, complicated hypertension and back pain (figure 3, online supplemental table 5). AF was registered as a secondary diagnosis in only 7% of all consultations. Of the primary diagnoses registered alongside a secondary diagnosis of AF, heart failure was the most severe in both women and men (9.9% women vs 16.5% men) (online supplemental table 6).

    Figure 3
    Figure 3

    Sex differences in early-onset AF comorbidity. The top 25 secondary diagnoses to AF consultations, as the proportion of secondary diagnoses given to women and men at AF consultations. *Statistical significant sex difference. AF, atrial fibrillation. NOS, Not otherwise specified.

    Discussion

    In this nationwide primary care study, we found the Norwegian prevalence of early-onset AF in 2019 to be 0.34%. At a group level, the early-onset AF population exerted a relatively low burden on the primary care services, where men had a significantly higher mean number of AF consultations per year than women, and a higher proportion of the men received primary care ER medical attention due to AF. The average group-level burden of disease was only representative of a small proportion of the early-onset AF population, as the early AF population displayed considerable variation in the need for healthcare.

    The prevalence and sex ratio of the early-onset AF population were comparable to previous reports,2–5 8 9 27–30 although only the oldest age group (>50 years) displayed a traditional male-to-female AF ratio of 3:1.28 30 For the youngest individuals, we observed a reduced sex difference in prevalence in line with previous reports from the UK between the years 1994 and 1998, in patients <44 years,7 and from Scotland between the years 2001 and 2002 in patients <45 years.8 In comparison, Kjerpeseth et al reported a similar prevalence for men and women <45 years of age in Norwegian national hospital data in the period 2008–2014,3 while Stefansdottir et al found a 3:1 (men: women) ratio for AF prevalence in the youngest AF patients (20–54 years) in hospital data from Iceland.28 Complications during pregnancy act as a recognised women-specific risk factor for AF in young women and may improve the diagnostic assessment of young women presenting with AF in primary care.31

    The average early-onset AF patient had a mean number of one primary care consultation per year due to AF, in line with a report by Murphy et al,8 thus suggesting a patient group with a relatively low disease burden. At a group level, we found fewer AF consultations in primary care for the youngest AF group which may reflect an initially healthier population, with less comorbidity and a need for preventive measures. Since the severity of AF symptoms often progresses with time,32 33 young patients may have less severe symptoms due to a shorter history of the disease. De With et al found that patients with no comorbidities were more prone to have familial AF.34 Despite the complicated nature of the underlying biological pathways of AF,35 36 multiple studies have established a heritability of AF, more pronounced for early-onset AF.29 37 38

    In general, women use primary care services at a higher frequency compared with men, regardless of age and marital status,39–41 and also when adjusting for sex-specific morbidity and reproduction.42 Our observations of a reversed sex ratio for AF consultations on a group level are consistent with the findings of Murphy et al, who also reported a higher contact rate for young men with AF compared with women.8 Our analyses of individual burden reflected the group-level sex differences, in which significantly more women had a low individual burden, and significantly more men had an intermediate individual burden. In contrast, for high or heavy individual burden, there was no sex difference, which indicates that non-sex-specific factors contribute to an increased need for medical attention in approximately 10% of the early-onset AF population.

    When we examined the distribution of AF consultations between the PCP and primary care ER services, we demonstrated a striking difference between women and men. The proportion of patients who were ever in contact with their PCP due to AF was similar for both sexes, but a higher proportion of men had additional contact with an ER service, which may indicate more urgent needs for medical attention due to AF for men. Only 3% of young men with new-onset AF were in contact with an ER service only, suggesting a more rapid need for additional PCP follow-up for young men around the new onset of AF. Sex differences in primary care burden in our early-onset AF population are thus not indisputable in accordance with previous AF studies, describing women with more frequent and pronounced symptoms12 13 18 and more affected QoL.14 15 Our observations were somewhat unexpected as they reflect a higher burden of early-onset AF for men than for women. The reasons for more frequent and extensive follow-up in the primary care for men than for women with early-onset AF may be complex. A higher cardiovascular risk profile for men in the study population could be one possible explanation, as the comorbidity profile was in line with previous reports on sex-specific comorbidity in AF.16 18 43 Also, more persistent AF in men15 may lead to closer monitoring. In the ISAF study, the lowest use of antiarrhythmic drugs against AF was reported in the young, and in particular in women.9 Whether or not sex differences in antiarrhythmic treatment represent an undertreatment of young women, a higher use of antiarrhythmic drugs among men may entail a closer follow-up in primary care. Men receive interventional treatment of AF to a greater extent than women,44 45 which may lead to closer primary care follow-up before and after treatment. Sex differences in health literacy among young AF patients may also have an impact. Several German population-based surveys have reported a correlation between the number of consultations with a physician and the patient’s health literacy,46 47 where >2 annual consultations were associated with reduced health literacy.

    Strengths and limitations

    A major strength of our study is the near complete registration of all residents in Norway diagnosed with early-onset AF. Studies based on diagnosis codes from hospital records include only individuals with AF receiving in- or outpatient hospital treatment, excluding patients only treated in a primary care setting. Therefore, it was advantageous to calculate the prevalence of early-onset AF in 2019 based on a confirmed early-onset AF diagnosis at any time within the study period, combined with residential status in 2019. We strengthened the results for group-level burden by calculating a 5-year average, as individual variation in time could affect the results when subdividing the cohort by sex and age. Registration of diagnosis codes in KUHR is directly linked to financial reimbursement from the health authorities, limiting selection bias of patient cases. An inherent limitation of register-based studies is the validity of the reported data. Sporaland et al found the correspondence between patient records and the ICPC-2 diagnosis codes in ordinary consultations due to all-cause to be 85.3% in the Norwegian primary care.20 In comparison, the validity of in-hospital AF diagnosis codes has been shown to be >90%.48–50 Hospital-based registry studies of AF often require at least two registered AF diagnoses, but we chose to define AF as ≥1 ICPC-2 AF diagnosis code, which is similar to the approach of other primary care studies.6–8 10 KUHR holds limited data on comorbidity since there are neither financial incentives nor a requirement in primary care to add secondary diagnoses for financial reimbursement.

    Conclusions

    In this nationwide registry-based primary care study, we found the Norwegian early-onset AF population to have a low prevalence and group-level burden, in line with previous reports. Nevertheless, we revealed a substantial individual variation and significant sex differences in primary care burden, with a higher annual consultation rate as well as more frequent use of ER consultations for men than women. Young individuals with AF are often grouped as <50 years of age in registry studies, but our observations suggest a need for more differentiated age groups to fill the knowledge gaps in burden and sex differences for early-onset AF.

    Data availability statement

    Data may be obtained from a third party and are not publicly available. The data underlying this manuscript cannot be shared according to guidelines on receipt of KUHR datasets.

    Ethics statements

    Patient consent for publication

    Ethics approval

    The study was approved by the Norwegian Regional Ethics Committee South-East (2009/2224).

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    Supplementary materials

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    Footnotes

    • Contributors All authors contributed to the conception of the study and the manuscript. SMK and SN were responsible for the analyses. IEC is the guarantor.

    • Funding The study was funded by the South-Eastern Norway Regional Health Authority (2019122), the Research Council of Norway (287086), Vestre Viken Hospital Trust, afib.no—the Norwegian Atrial Fibrillation Research Network and 'Indremedisinsk Forskningsfond' at Bærum Hospital.

    • Disclaimer SMK was supported by Vestre Viken Hospital Trust, the South-Eastern Norway Regional Health Authority and is employed by AstraZeneca. IEC was supported by the Research Council of Norway, afib.no—the Norwegian Atrial Fibrillation Research Network, and 'Indremedisinsk Forskningsfond' at Bærum Hospital. None of the funders had any part in planning of the study or writing of the manuscript.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.