Background:Despite growing initiatives to promote partially virtual care, there is still a lack of comprehensive data describing its use, patient characteristics, and medication management practices. Objective:This study aimed to examine the use of partially virtual care in the management of cardiovascular disease. Methods:We used nationwide Danish registries to identify all patients with a first-time diagnosis of atrial fibrillation (AF), heart failure (HF), pulmonary embolism (PE), or acute coronary syndrome (ACS) between 2019 and 2023. Patients were categorized as receiving partially virtual care if followed up at least once virtually or in-person care if seen solely in-person. We evaluated temporal changes in the use of partially virtual care and calculated the odds of receiving partially virtual care vs in-person care and the prevalence of initiating guideline-directed medical therapy (GDMT). For GDMT initiation, the exposure was instead the type of the patient's first follow-up visit. Multivariable logistic regression was used to estimate the odds of receiving partially virtual care, adjusted for frailty score, residence, and period of diagnosis. Separate multivariable logistic regression models were then used to estimate adjusted average differences in the prevalence of GDMT initiation between virtual and in-person follow-up among patients not already on the medication, accounting for frailty score, residence, and period of diagnosis. Results:In total, 45,919 patients with AF, 30,482 with HF, 12,451 with PE, and 12,435 with ACS were followed up. Among these, 27.3% (AF: 12,517/45,919), 51.7% (HF: 15,749/30,482), 47.5% (PE: 5918/12,451), and 37.2% (ACS: 4627/12,435) had partially virtual follow-up. The use of partially virtual follow-up increased during the COVID-19 pandemic and remained high afterward. In 2023, 17.4% (475/2731) to 35.3% (876/2481) of patients' first follow-up visits were virtual, depending on the condition. Patient-specific factors significantly associated with partially virtual care were patients residing in cities for those with AF (odds ratio [OR] 1.27, 95% CI 1.21-1.34), HF (OR 1.38, 95% CI 1.31-1.46), and PE (OR 1.14, 95% CI 1.04-1.24), but not for patients with ACS, and "high frailty" for those with AF (OR 1.63, 95% CI 1.48-1.80) and PE (OR 1.53, 95% CI 1.29-1.81). A large percentage of patients were on GDMT prior to the first follow-up visit. Differences in new initiation of GDMT were small in absolute terms across conditions, regardless of virtual or in-person follow-up; for example, for patients with HF, 2.23% initiated sodium-glucose cotransporter-2 inhibitors following a virtual visit, vs 4.47% after an in-person visit (prevalence difference -2.24%, 95% CI, -2.61 to -1.87). Conclusions:Among patients who received follow-up, a considerable proportion of patients with cardiovascular disease (from 12,517/45,919, 27.3% to 15,749/30,482, 51.7%) received partially virtual care. The odds of receiving partially virtual care varied significantly based on patient characteristics, particularly place of residence and frailty score. Finally, small absolute differences were found in the initiation of new GDMT.

BACKGROUND:Direct oral anticoagulants (DOACs) and corticosteroids are frequently co-prescribed in clinical practice. While both drug classes independently increase bleeding risk, the impact of their concurrent use remains unclear. AIM:To systematically review the literature on bleeding outcomes associated with combined DOAC and corticosteroid use. METHODS:We conducted a systematic review following PRISMA guidelines. PubMed, Web of Science, and Scopus were searched for studies reporting bleeding in patients receiving both DOACs and corticosteroids. Cumulative incidences of any bleeding and major bleeding (MB) were estimated using a random-effects model, and study quality assessed using the Newcastle-Ottawa Scale and the Cochrane RoB2. Subgroup analyses were performed for patients treated for atrial fibrillation (AF) and venous thromboembolism (VTE). RESULTS:Nine studies including 87,209 patients were included. The weighted cumulative incidence of any bleeding was 7.0% (95% CI 3.96-12.01%), and of MB 6.6% (95% CI 6.21-6.97%). Heterogeneity was high for any bleeding in the overall and in the AF populations, likely reflecting differences in patient characteristics, corticosteroid exposure, follow-up duration, and study design, whereas heterogeneity was minimal in the VTE subgroup. Variability in bleeding definitions, limited reporting of corticosteroid dose and duration, and absence of stratification by DOAC type/dose or bleeding site further contributed to differences in observed incidences. CONCLUSIONS:Available evidence suggests a clinically relevant incidence of bleeding among patients receiving concomitant DOAC and corticosteroid therapy. Clinicians should carefully evaluate the risk-benefit profile, monitor patients closely, and consider preventive strategies. Future studies are needed to improve risk characterization in this common clinical scenario. PROSPERO REGISTRATION:CRD420251045710.

Background and Aims Anticoagulation therapy in patients with atrial fibrillation (AF) has changed over time, particularly following the introduction of direct oral anticoagulants. However, it is unknown how the uptake of anticoagulation therapy and the related clinical outcomes in elderly patients with AF have changed over time. Methods Patients with new-onset AF were included and divided into three age groups: older adults (65–74 years), elderly (75–84 years), and very elderly (≥85 years). Temporal trends in the initiation of oral anticoagulants (OACs), the stroke-free survival, major bleedings including intracerebral haemorrhage (ICH), and all-cause mortality were investigated from 1999 to 2022. Results In total, 243 938 patients were included, of whom 89 184 (36.6%) were older adults, 99 002 were elderly (40.6%), and 55 752 (22.8%) were very elderly. The proportion of very elderly patients with AF receiving OACs was 71% in 2022. The absolute improvement in the 5-year probability of stroke-free survival was 10.1% in the older adult patients, 12.8% in the elderly patients, and 3.5% in the very elderly patients. The 5-year absolute risk of ICH increased among the elderly and very elderly AF patients. Conclusions Over the past two decades, the risk of stroke decreased significantly among all age groups, with no subsequent increase in the risk of bleeding among older adults in an era where OACs were almost fully implemented. In the very elderly patients aged ≥85 years, the risk of stroke only slightly improved over time, with an increase in the risk of ICH.

BACKGROUND AND AIMS:Glucagon-like peptide-1 receptor agonists (GLP-1 RA) carry side-effects such as dizziness and nausea related to increased vagal tone. This study investigated associations between GLP-1 RA use and the risk of vagal activity related (VAR) events. METHODS:Using the Danish health registers, patients with type 2 diabetes mellitus (T2DM) first-time initiated on GLP-1 RA (exposure) or SGLT-2i (active control) were identified between January 2010 and October 2022. Standardized 1-year absolute risks of VAR events (syncope, fractures, bradyarrhythmia, or cardiac device implantation) were computed to compare risk associated with GLP-1 RA and SGLT-2i initiation. Complementary analyses in patients treated for obesity were performed as well. RESULTS:During the study period, 50 076 and 73 138 patients with T2DM were initiated on GLP-1 RA (47% women, median age: 59 years [IQR: 50-68]) or SGLT-2i (39% women, median age: 64 years [IQR: 55-72]). Comorbidity was equally prevalent. The standardized 1-year absolute risk of syncope was 0.58% (95% CI: 0.51%-0.66%) among patients initiated on GLP-1 RA and comparable to patients initiated on SGLT-2i (0.56% [95% CI: 0.50%-0.62%]). 1-year risks of fractures, bradyarrhythmia, and cardiac device implantation were equally low and with corresponding standardized risk ratios of 0.90 (95% CI: 0.79-1.01), 0.97 (95% CI: 0.67-1.28), and 0.86 (95% CI: 0.62-1.10), respectively. No associations were found in the group treated for obesity either. CONCLUSIONS:In nationwide cohorts of patients treated for T2DM or obesity, initiation of GLP-1 RA was not associated with an elevated risk of VAR events. Despite a proposed argumentation of vagal activity, GLP-1 RA use was not associated with an increased risk in real-life users.

BACKGROUND:Peak oxygen consumption (pVO₂) is a key predictor of mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF). METHODS:From December 2022 to September 2023, patients with new-onset HFrEF were prospectively enrolled from a heart failure outpatient clinic. All patients underwent at least 12 weeks of guideline-directed medical therapy (GDMT) initiation and management, including physical training and education. Cardiopulmonary exercise testing (CPET), medication, echocardiography, and clinical data were collected at baseline and after 12 weeks. Associations with pVO₂ changes were examined using univariable and multivariable regression analyses. RESULTS:We included 48 patients (median age 73 years, 20.8% women) with baseline left ventricular ejection fraction (LVEF) of 30% ± 7 and pVO₂ of 18.1 ± 5.6 mL/min/kg. After 12 weeks, pVO₂ increased by 2.2 mL/min/kg (95% CI: 1.3-3.1, p < 0.001) and LVEF improved to 44% (+14% [95% CI: 12-17, p < 0.001]). In the multivariable model, reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and body mass index (BMI) were associated with higher pVO₂ (β = -1.11 [95% CI: -2.15 to -0.06, p = 0.039]; β = -1.62 [95% CI: -2.99 to -0.25, p = 0.023]). Higher left atrial end-systolic volume index (LAESVi) was also associated with increased pVO₂ (β = 0.23 [95% CI: 0.10-0.35, p = 0.001]). CONCLUSION:GDMT was associated with improvements in cardiorespiratory fitness and LVEF in patients with new-onset HFrEF. Reductions in NT-proBNP, decreases in BMI, and increases in LAESVi were independently associated with pVO₂ improvements after 12 weeks.

INTRODUCTION:Long-term cardiac monitoring has become more accessible with the advent of consumer-oriented wearable devices. Smartwatches (SWs) hold promise for extended rhythm monitoring owing to their availability and direct electronic health record (EHR) integration. We studied the clinical consequences of SW implementation in patients with palpitations. METHODS:Patients referred for palpitations or with inconclusive diagnostics were issued a SW for up to three months. They were instructed to take an SW-electrocardiogram (ECG) during symptoms and transfer it to the EHR. A cardiologist interpreted the ECGs, diagnosed the patient and initiated relevant clinical actions. RESULTS:We included 50 patients with a median age of 57 years (IQR: 45-64), 56% women. The following ECG diagnoses were made: 20 (40%) had sinus rhythm, six (12%) had extrasystoles and 24 (48%) had clinically relevant arrhythmias. Consequently, 25 (50%) completed their arrhythmia evaluation, whereas clinical actions were taken in 25 (50%). Notably, more than 20% underwent an electrophysiology study and ablation. Patients found the SW to be user-friendly with minimal impact on their daily life. CONCLUSIONS:SW use for symptom-based diagnosis had a high yield for both arrhythmia detection and completion of arrhythmia evaluation. Additional studies are needed to determine if SWs may replace traditional ECG monitoring. FUNDING:The project was funded by internal funds at the Department of Cardiology, Herlev and Gentofte University Hospital (HGH), Denmark. TRIAL REGISTRATION:As a quality assurance project, no ethical board approval was needed under Danish law. The study was approved by the HGH directors.

BACKGROUND The prognostic implications of early-onset atrial fibrillation (AF) in patients without coexisting cardiovascular conditions are not clear. OBJECTIVE This study aimed to investigate the long-term risk of stroke, heart failure (HF), and mortality in patients with early-onset AF. METHODS Using nationwide registers, we included adult patients with early-onset AF (aged 18-45 years) with a first-time AF diagnosis during 1999-2023 without co-existing cardiovascular conditions. All patients with AF were matched with a control group from the background population without AF. The long-term absolute risks of stroke, HF, and death were estimated and supplemented with standardized risk ratios (RRs) comparing patients with and without AF. RESULTS Among 7632 patients with AF (median age: 39 years, 71% men, 1.9% cancer, 2.1% diabetes), clinically relevant crude risks of stroke (20-year risk: 6.89%, 95% confidence interval [CI] 5.96%-7.82%), HF (20-year risk: 6.45%, 95% CI 5.60%-7.31%), and death (20-year risk: 7.10%, 95% CI 6.18%-8.02%) were observed. Comparing the AF cohort with a matched sample from the background population (median age: 38 years, 71% men, 1.1% cancer, 1.3% diabetes) revealed elevated standardized risks of stroke (RR: 2.00, 95% CI 1.67-2.33), HF (RR: 4.33, 95% CI 3.55-5.11), and death (RR: 1.37, 95% CI 1.17-1.57). CONCLUSION Early-onset AF in patients without concomitant cardiovascular conditions was associated with increased long-term risk of cardiovascular complications, most notably a 4-to 5-fold increased risk of HF. Hence, AF in otherwise healthy young patients should be considered an important marker of increased risks of a future cardiomyopathy and HF events.

Aims: Studies have reported excess risk of mortality associated with digoxin in atrial fibrillation (AF).This study sought to investigate if these findings could be replicated and whether a potential association could be explained by bias. Methods: Using Danish Nationwide registers, a nested-case control study from 2012 to 2022 was conducted in a cohort of patients with AF. Cases were defined as death of any cause and the exposure was treatment with digoxin compared with beta blockers/verapamil. To investigate bias, additional analyses with negative control outcomes as case definitions—in which we would not expect a plausible association (eg, nursing home admission)—were employed. Associations were reported as hazard ratios (HRs) with 95% confidence intervals (95% CI). Results: A total of 59,748 cases were identified and matched 1:10 with controls (53% men, median age: 84 [IQR: 77-89]). Digoxin was associated with increased rates of mortality in the entire cohort (HR 1.85, 95% CI 1.78-1.92) as well as subgroups such as patients with heart failure (HR 1.84, 95% CI 1.65-2.06), diabetes (HR 1.85, 95% CI 1.6-2.14), and kidney disease (HR 1.37, 95% CI 1.04-1.8). Significant associations with all negative control outcomes were also found, most notably nursing home admissions (HR 1.79, 95% CI 1.67-1.93). Conclusion: Digoxin use was associated with increased mortality in AF. However, negative control outcomes were also associated with digoxin use indicating that the described association between digoxin and mortality is likely not causal and being prescribed digoxin is merely a marker of more advanced disease and frailty.

Background Iron deficiency (ID) is common in patients with atrial fibrillation/flutter (AF), but its prognostic implications and optimal diagnostic criteria, particularly in those with and without heart failure (HF), remain unclear. This study assessed the associations between different ID definitions and clinical outcomes in patients with AF. Methods This Danish nationwide cohort study included 10 834 patients with AF who underwent iron studies between 2008 and 2019, stratified by HF status. ID was defined using four criteria: European Society of Cardiology (ESC) guidelines, ferritin <100 ng/mL, transferrin saturation (TSAT) <20% and serum iron ≤13 µmol/L. Associations between ID definitions and all-cause mortality, cardiovascular mortality and all-cause hospitalisation were evaluated using Cox regression models, adjusted for confounders. Results Prevalence of ID varied substantially across definitions, ranging from 36.2% to 62.7%. Over a median follow-up of 31 months, TSAT <20% was associated with increased all-cause and cardiovascular mortality in both HF (HR 1.25, 95% CI 1.14 to 1.37 and HR 1.31, 95% CI 1.14 to 1.49, respectively) and patients without HF (HR 1.39, 95% CI 1.18 to 1.64 and HR 1.54, 95% CI 1.18 to 2.00, respectively). Similarly, serum iron ≤13 µmol/L was associated with higher all-cause and cardiovascular mortality in HF (HR 1.44, 95% CI 1.31 to 1.58 and HR 1.42, 95% CI 1.24 to 1.63, respectively) and patients without HF (HR 1.67, 95% CI 1.41 to 1.97 and HR 1.46, 95% CI 1.13 to 1.89, respectively). ID defined by ESC guidelines or ferritin <100 ng/mL was not associated with mortality in either group but was linked to higher all-cause hospitalisation in patients with HF (HR 1.15, 95% CI 1.08 to 1.23 and HR 1.16, 95% CI 1.09 to 1.23, respectively). Conclusions ID defined by TSAT <20% or serum iron ≤13 µmol/L is associated with increased mortality in patients with AF, irrespective of HF status, highlighting these criteria as clinically relevant for risk stratification.

BACKGROUND:Renin-angiotensin system inhibitors (RASIs) are known teratogens, while statins are potentially teratogenic. The study examined prescribing patterns of RASIs and statins alongside use of concomitant contraception among all women of child-bearing age in Denmark. METHODS:Nationwide registers were used to identify all women aged 15-50 years on RASIs, statins or calcium-channel blockers (CCB) during 2000-2023. Concomitant contraception was categorized as oral pill, implant, intrauterine device (IUD), or non-use. The duration of protection was assumed to be 180 days for oral contraceptives, two years for implants, and four years for IUDs. RESULTS:In total, 141,351 women (median age 44 years) on RASIs, 79,814 (median age 45 years) on statins, and 86,173 (median age 44 years) on CCBs were included. The contraceptive coverage was 32.8% for RASI users, 25.2% for statin users and 30.8% for CCB users. Among RASI users on contraceptives, 66.4 % used oral contraceptives, 32.9% had IUDs, and 0.7 % had implants. For statin users, 66.3 % used oral contraceptives, 32.7% had IUDs, and 1.0 % had implants. Of the women on RASIs or statins 7.2% were on both drugs. For women aged 27-35 years, contraceptive use was 48.0 % among RASIs users, 44.5% for statin users and 39.9% for CCB users. CONCLUSION:From 2000-2023, 141,351 women of child-bearing age were prescribed RASIs and 79,814 prescribed statins, most without concomitant prescription contraceptives, suggesting a public health risk of teratogenic exposure. Future studies should investigate the extent and impact of exposure during pregnancy.

Risk of cardiovascular side effects associated with the agonistic effect on the sympathetic nervous system provided by the medical treatment of ADHD is continuously debated. Any causal relationship has yet to be proven but observational findings suggest an increased risk of cardiovascular disease associated with treatment - especially higher doses over longer periods. Follow-up with clinical assessment, blood pressure, and resting heart rate is advised. Electrocardiograms and measurements of lipid- and HbA1c levels might also often be advisable in adults, as argued in this review.

BACKGROUND:Concerns regarding side-effects of beta-blockers (BBs) are frequent but data regarding the incidence of side-effects are conflicting and real-world data are sparse. Hence, we aimed to investigate the absolute and relative risks of BB side-effects in clinical practice. METHODS:Using Danish nationwide registers, we included Danish hypertensive patients initiating antihypertensive treatment with a BB or calcium-channel blocker (CCB). We computed crude as well as standardized 1-year risks and adjusted risk ratios of BB side-effects (depression, anxiety/insomnia, gastrointestinal side-effects, erectile dysfunction, and dizziness/fainting) compared with CCB treatment. RESULTS:We included 64,722 patients initiating treatment with a BB and 181,880 patients initiating treatment with a CCB. In patients initiated on BB, the standardized 1-year risk of any outcome, erectile dysfunction exempt, was 13.7% (95% CI: 13.4%-13.9%). The 1-year risk of specific BB side-effects was the highest for anxiety/insomnia (6.2%, 95% CI: 6.0%-6.3%), gastrointestinal side-effects (4.6%, 95% CI: 4.4%-4.7%), and erectile dysfunction (4.7%, 95% CI: 4.5%-4.9%). The risk of side-effects was consistently increased when comparing BB treatment with CCBs including depression (Risk Ratio [RR] 1.48, 95% CI 1.41-1.55), anxiety/insomnia (RR 1.53, 95% CI 1.47-1.59), gastrointestinal side-effects (1.31, 95% CI 1.25-1.36), and dizziness/fainting (RR 1.50, 95% CI 1.38-1.61), but not erectile dysfunction (RR 0.91, 95% CI, 0.85-0.96). CONCLUSIONS:In a large nationwide cohort, the incidence of BB side-effects was clinically relevant and consistently increased compared with CCBs with the exception of erectile dysfunction, which carried similar risks for both treatments.

Aims:Fluoroquinolones (FQ) have been associated with aortic aneurysm and aortic dissection (AA/AD) resulting in an official warning. Recently, large-scale epidemiological studies failed to confirm this. Methods and Results:The current study aimed to scrutinize the FQ-AA/AD association through a retrospective nested case-cohort analysis supplemented with animal experimentation. FQ exposure was not associated with increased AA/AD hazard ratios in main and high-risk (elderly ≥65 years, hypertensive, and prevalent aortic disease) populations. Additionally, FQ did not cause increased mortality or aortic interventions in aortic disease patients. In addition, in animal experimentation, ciprofloxacin did not enlarge aortic diameters nor increase arterial stiffness. Conclusion:Conventional use of FQ should not be avoided when clinically indicated.

Abstract Background Cardiometabolic disorders, including hypertension, type-2 diabetes, and hyperlipidemia are increasingly prevalent among younger people. Consequently, women of child-bearing age may be prescribed renin-angiotensin system (RAS) inhibitors and statins. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known teratogens. Statins are considered possibly teratogenic. In Denmark, ACEIs and ARBs have a ‘Do not use’ recommendation in pregnancy while statins ‘Should not be used’ in pregnancy. Previous studies have reported widespread use of RAS inhibitors without concomitant contraception among women of child-bearing age. This study investigated the situation in Denmark. Purpose To examine prescribing patterns of RAS inhibitors and statins alongside use of concomitant contraception among women of child-bearing age in Denmark. Methods Using nationwide Danish registers, women aged 15–50 years initiating ACEIs, ARBs and statins during 1995–2021 were identified and use of concomitant contraception was evaluated. Contraception was categorized as oral pill, implant, intrauterine device (IUD), or non-use. The duration of protection was assumed to be 1 year for oral contraceptives, 2 years for implants and 4 years for IUDs. Where multiple types of contraceptives were retrieved by individual patients, they were categorized as taking the contraceptive retrieved most recently. Data on non-prescription contraceptives were unavailable, e.g., condoms. Women unable to conceive due to infertility were excluded. Results 79 547 women (median age: 44 years; [interquartile range (IQR): 39–47]) on ACEIs, 64 326 women (median age: 44 years [IQR: 38–48]) on ARBs, and 71 499 women (median age: 45 years [IQR: 40–48]) on statins were included (Figure 1). Correspondingly, 69.1%, 62.8%, and 73.5% were not on contraceptives when starting treatment. Among women prescribed contraception: 70.2%/56.2%/63.1% were on oral contraceptives, 25.3%/30.9%/26.6% had IUDs and 4.5%/12.9%/10.3% had implants, respectively (Figure 1). Younger patients aged 15–29 years were least likely to be unprotected with 41.8%/29.7%/33.4% being unprotected. Among women aged 25 to 35 years the percentage of unprotected women was 51.3%/41.1%/47.7%. Older patients were more likely to have IUDs. Conclusion Substantial numbers of women of child-bearing age were prescribed ACEIs, ARBs and statins from 1995–2021. Most were not prescribed contraceptives. The lack of prescribed pregnancy protection was prevalent even among the youngest women aged 15–29 years and women aged 25 to 35 years, who are the most likely to become pregnant—inferring a potential risk of teratogenic exposure during pregnancy (Figure 2). Subsequent studies should investigate the extent of exposure to ACEIs, ARBs, and statins during pregnancy and the impact of the exposure on pregnancy outcomes.Figure 1 Contraceptive useFigure 2 Study rationale

Background and Aims: Fluoroquinolones (FQ) have been linked to aortic aneurysms and dissections (AA/AD), resulting in an official warning. However, recent large-scale epidemiological studies have reported lack of FQ-AA/AD association. This study aimed to scrutinize FQ-AA/AD risk by implementing a combined epidemiological and experimental approach. Methods: Danish nationwide registers (2003-2021) were used for a nested case-control analysis. FQ-AA/AD risk was evaluated in a main and high-risk FDA cohort. Further, mortality and aortic interventions linked to FQ were investigated in patients with aortic disease. Additionally, ciprofloxacin (100 mg/kg/day, 2x2 weeks) was administered to wild-type, hypertensive or Marfan mice. Aortic diameters and pulse wave velocity (PWV) were measured longitudinally to investigate aortic remodelling. Results: The main cohort comprised 5.10 million individuals with 58,919 cases and 1,767,510 sampled controls. Compared with amoxicillin exposure. FQ exposure was not associated with increased AA/AD risk (30-day hazard ratios (HR) 1.00 [95% confidence intervals (CI): 0.74-1.34]; 90-day HR 1.07 [CI 0.94-1.22]; 1-year HR 0.95 [0.90-1.01]). In a high-risk cohort, there was no FQ-AA/AD association (30-day HR 0.83 [0.61-1.12]; 90-day HR 0.99 [0.86-1.15]; 1-year HR 0.97 [0.90-1.05]). In patients with aortic disease, FQ were not associated with increased aortic interventions or mortality (30-day HR 0.98 [0.79-1.22]; 90-day HR 1.06 [0.95-1.19]). Additionally, ciprofloxacin did not affect aortic diameters or PWV in wild type, hypertensive, and Marfan mice, while differences between models proved the sensitivity of the methodology. Conclusion: The data clearly do not support the current precautions and warnings pertaining to risks of aortopathies and FQ should not be discouraged when clinically indicated.

AIMS:Multiple health administrative databases can be individually linked in Aotearoa New Zealand, using encrypted identifiers. These databases were used to develop cardiovascular risk prediction equations for patients with known cardiovascular disease (CVD). METHODS AND RESULTS:Administrative health databases were linked to identify all people aged 18-84 years with known CVD, living in Auckland and Northland, Aotearoa New Zealand, on 1 January 2014. The cohort was followed until study outcome, death, or 5 years. The study outcome was death or hospitalization due to ischaemic heart disease, stroke, heart failure, or peripheral vascular disease. Sex-specific 5-year CVD risk prediction equations were developed using multivariable Fine and Gray models. A total of 43 862 men {median age: 67 years [interquartile range (IQR): 59-75]} and 32 724 women [median age: 70 years (IQR: 60-77)] had 14 252 and 9551 cardiovascular events, respectively. Equations were well calibrated with good discrimination. Increasing age and deprivation, recent cardiovascular hospitalization, Mori ethnicity, smoking history, heart failure, diabetes, chronic renal disease, atrial fibrillation, use of blood pressure lowering and anti-thrombotic drugs, haemoglobin A1c, total cholesterol/HDL cholesterol, and creatinine were statistically significant independent predictors of the study outcome. Fourteen per cent of men and 23% of women had predicted 5-year cardiovascular risk <15%, while 28 and 24% had ≥40% risk. CONCLUSION:Robust cardiovascular risk prediction equations were developed from linked routine health databases, a currently underutilized resource worldwide. The marked heterogeneity demonstrated in predicted risk suggests that preventive therapy in people with known CVD would be better informed by risk stratification beyond a one-size-fits-all high-risk categorization.

Background and Aims A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis.Methods Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018-21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication. The absolute risks of first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome were reported comparing medical cannabis use with no use.Results Among 1.88 million patients with chronic pain (46% musculoskeletal, 11% cancer, 13% neurological, and 30% unspecified pain), 5391 patients claimed a prescription of medical cannabis [63.2% women, median age: 59 (inter-quartile range 48-70) years] and were compared with 26 941 control patients of equal sex- and age composition. Arrhythmia was observed in 42 and 107 individuals, respectively, within 180 days. Medical cannabis use was associated with an elevated risk of new-onset arrhythmia {180-day absolute risk: 0.8% [95% confidence interval (CI) 0.6%-1.1%]} compared with no use [180-day absolute risk: 0.4% (95% CI 0.3%-0.5%)]: a risk ratio of 2.07 (95% CI 1.34-2.80) and a 1-year risk ratio of 1.36 (95% CI 1.00-1.73). No significant association was found for acute coronary syndrome [180-day risk ratio: 1.20 (95% CI 0.35-2.04)].Conclusions In patients with chronic pain, the use of prescribed medical cannabis was associated with an elevated risk of new-onset arrhythmia compared with no use-most pronounced in the 180 days following the initiation of treatment. Structured Graphical Abstract Medical cannabis and cardiovascular risk. A graphical representation of the main findings showing the risk of new-onset arrhythmia and acute coronary syndrome in patients with chronic pain according to the use of medical cannabis. AR, absolute risk; CI, confidence interval.

>Dear editor,Fluoroquinolones （FQs） are a class of antibiotics used to treat bacterial infections,such as lower respiratory,gastrointestinal,and urinary tract infections.Due to its broad-spectrum action and wide availability,it is a commonly prescribed group of antibiotics worldwide. 1