Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral bleeding: the AF SPICE protocol.

INTRODUCTION: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity. METHODS AND ANALYSIS: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72 hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3 months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up. ETHICS AND DISSEMINATION: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice. TRIAL REGISTRATION NUMBER: NCT05134454.

Identifying factors explaining practice variation in secondary stroke prevention in primary care: a cohort study based on all patients with ischaemic stroke in the Stockholm region.

OBJECTIVES: The aim of this study was to describe the practice variation in dispensation of secondary stroke preventive drugs among patients at different primary care centres (PCCs) in Stockholm region and to identify factors that may explain the variation. DESIGN: Cohort study using administrative data from the Stockholm region. SETTING: Stockholm Health Care Region, Sweden, serving a population of 2.3 million inhabitants, hospital and PCC data. PARTICIPANTS: All patients (n=9761) with ischaemic stroke treated in hospital from 1 July 2009 to 30 June 2014 were included. Of these, 7562 patients registered with 187 PCCs were analysed. Exclusion criteria were; deceased patients, age <18, haemorrhagic stroke and/or switching PCC. PRIMARY AND SECONDARY OUTCOME MEASURES: As primary outcome the impact of PCC organisation variables and patient characteristics on the dispensation of statins, antiplatelets, antihypertensives and anticoagulants were analysed. Secondarily, the unadjusted practice variation of preventive drug dispensation of 187 PCCs is described. RESULTS: There was up to fourfold practice variation in dispensation of all secondary preventive drugs. Factors associated with a lower level of dispensed statins were privately run PCCs (OR 0.91 (95% CI 0.82 to 1.00)) and the patient being woman. Increased statin use was associated with a higher number of specialists in family medicine (OR 1.03 (95% CI 1.01 to 1.05)) and a higher proportion of patients registered with a specific physician (OR 1.37 (95% CI 1.11 to 1.68)). Women had on average a lower number of dispensed antihypertensives. CONCLUSIONS: A high practice variation for dispensation of all secondary preventive drugs was observed. Patient and PCC level factors indicating good continuity of care and high level of general practitioner education were associated with higher use of statins. Findings are of importance to policymakers as well as individual providers of care, and more research and actions are needed to minimise inequality in healthcare.

Recording a diagnosis of stroke, transient ischaemic attack or myocardial infarction in primary healthcare and the association with dispensation of secondary preventive medication: a registry-based prospective cohort study.

OBJECTIVES: The aim of this study was to explore whether recording in primary care of a previously recorded hospital diagnosis was associated with increased patient utilisation of recommended medications. DESIGN: Registry-based prospective cohort study. SETTING AND PARTICIPANTS: 19 072 patients with a hospital discharge diagnosis of transient ischaemic attack (TIA), stroke or acute coronary syndrome from hospitals in Stockholm County 2010-2013 were included in the study. MAIN OUTCOME MEASURE: The outcome of the study was medication dispensation as a marker of adherence to recommended medications. Adherence was defined as having had at least two filled prescriptions in the third year following hospital discharge. RESULTS: Recording a diagnosis was associated with higher utilisation of all recommended medications with the exception of antihypertensives in patients with TIA. The differences between the groups with and without a recorded diagnosis remained after adjusting for age, sex, index year and visits to private practitioners. Dispensation of antithrombotics was high overall, 80%-90% in patients without a recorded diagnosis and 90%-94% for those with a diagnosis. Women with recorded ischaemic stroke/TIA/acute coronary syndrome were dispensed more statins (56%-71%) than those with no recorded diagnosis (46%-59%). Similarly, 68%-83% of men with a recorded diagnosis were dispensed statins (57%-77% in men with no recorded diagnosis). The rate of diagnosis recording spanned from 15% to 47% and was especially low in TIA (men 15%, women 16%). CONCLUSION: Recording a diagnosis of TIA/stroke or acute coronary syndrome in primary care was found to be associated with higher dispensation of recommended secondary preventive medications. Further study is necessary in order to determine the mechanisms underlying our results and to establish the utility of our findings.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained.

Renal function estimations and dose recommendations for dabigatran, gabapentin and valaciclovir: a data simulation study focused on the elderly.

OBJECTIVES: The thrombin inhibitor dabigatran is mainly excreted by the kidneys. We investigated whether the recommended method for estimation of renal function used in the clinical trials, the Cockcroft-Gault (CGold) equation and the estimated glomerular filtration rate (eGFR) modification of diet in renal disease equation 4 (MDRD4), differ in elderly participants, resulting in erroneously higher dose recommendations of dabigatran, which might explain the serious, even fatal, bleeding reported. The renally excreted drugs gabapentin and valaciclovir were also included for comparison. DESIGN: A retrospective data simulation study. PARTICIPANTS: Participants 65 years and older included in six different studies. MAIN OUTCOME MEASURE: Estimated renal function by CG based on uncompensated ('old Jaffe' method) creatinine (CGold) or by MDRD4 based on standardised compensated P-creatinine traceable to isotope-dilution mass spectrometry, and the resulting doses. RESULTS: 790 participants (432 females), mean age (±SD) 77.6±5.7 years. Mean estimated creatinine clearance (eCrCl) by the CGold equation was 44.2±14.8 ml/min, versus eGFR 59.6±20.7 ml/min/1.73 m(2) with MDRD4 (p<0.001), absolute median difference 13.5, 95% CI 12.9 to 14.2. MDRD4 gave a significantly higher mean dose (valaciclovir +21%, dabigatran +25% and gabapentin +37%) of all drugs (p<0.001). With MDRD4 58% of the women would be recommended a full dose of dabigatran compared with 18% if CGold is used. CONCLUSIONS: MDRD4 would result in higher recommended doses of the three studied drugs to elderly participants compared with CG, particularly in women, and thus increased the risk of dose and concentration-dependent adverse reactions. It is important to know which method of estimation of renal function the Summary of Products Characteristics was based on, and use only that one when prescribing renally excreted drugs with narrow safety window. Doses based on recently developed methods for estimation of renal function may be associated with considerable risk of overtreatment in the elderly.