Aims To assess the association between statin use and cataract surgery according to different statin treatment durations in patients with different cardiovascular risk profiles.Methods and results We performed a nested case-control study using Danish registries, covering the period from 1 January 1996 to 31 December 2020. We defined cases as surgically treated cataract patients, matched in a 1:1 ratio by sex and age with controls not undergoing cataract surgery. The exposure of interest was statin use in different durations (1, 5 and 10 years) compared with never use of statins. Conditional logistic regression provided adjusted HRs and corresponding 95% CIs in subgroups defined by established atherosclerotic cardiovascular disease, diabetes, hypertension and individuals without these comorbidities. We identified 505 150 cataract surgery cases and found no increased HR of cataract surgery with statin treatment at any duration in any of the subgroups with established atherosclerotic cardiovascular disease, diabetes or hypertension.Conclusion Our findings do not support a possible association between long-term statin use and cataract in patients with established atherosclerotic cardiovascular disease, diabetes or hypertension. Although we found an association between statin use and cataract in individuals without these comorbidities, increasing durations of statin use did not yield higher cataract surgery rates.

Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cardiovascular outcomes in patients with type 2 diabetes, but few studies have studied the risk of out-of-hospital cardiac arrest (OHCA). We investigated whether GLP-1 RA use reduce OHCA risk in type 2 diabetes when compared to dipeptidyl peptidase-4 inhibitor (DPP-4i) use. Methods: We identified all patients having a redeemed prescription of a glucose-lowering drug between 1995 and 2019 and excluded patients with a first-time redeemed prescription consisting of insulin. Within this cohort, we nested a case-control population comprising all OHCA-cases from presumed cardiac causes between 2013 and 2019. OHCA-cases were matched 1:5 to non-OHCA controls of the same sex and age on the date of OHCA. The odds ratios (ORs) and corresponding 95% confidence intervals (95%-CIs) of OHCA were reported comparing GLP-1 RAs versus DPP-4is. Results: We identified 3,618 OHCA-cases from presumed cardiac causes and matched them to 18,090 non-OHCA controls. GLP-1 RAs were used by 269 (7.44%) cases and 1297 (7.17%) controls, and conferred no increase in the overall odds of OHCA compared with DPP-4i use (OR:0.89, 95%-CI 0.74-1.07). However, stratification according to sex revealed that OHCA risk was significantly reduced in women (OR:0.59, 95%-CI 0.40-0.86) but not in men (OR:1.01, 95%-CI 0.82-1.26, P-value interaction:0.0093). The OR of OHCA did not vary significantly when stratifying for age, duration of diabetes, chronic kidney disease, or presence of cardiovascular disease. Conclusion: Our findings indicate that GLP-1 RA use is not associated with a reduced risk of OHCA in Danish individuals with type 2 diabetes when compared to DPP-4is.

AIMS:Proton pump inhibitors (PPIs) impair cardiac repolarization, prolong the QT interval, and may potentially be pro-arrhythmic. However, the risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We studied whether past or current PPI use is associated with OHCA in the general population. METHODS AND RESULTS:We conducted a nationwide nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA-controls from the general population. Exposure to PPI was categorized into three mutually exclusive groups of current-, past-, and non-use. Conditional logistic regression analyses with adjustments for risk factors of OHCA were used to calculate the odds ratio (OR) of OHCA comparing PPI use with non-users. We identified 46 578 OHCA cases and 232 890 matched non-OHCA controls (mean: 71 years, 68.8% men). PPI was used by 8769 OHCA-cases and 21 898 non-OHCA controls, and current use of PPI was associated with increased odds of OHCA compared with non-users [OR: 1.32 (95% CI: 1.28-1.37)], while past use conferred no increase in the odds of OHCA [OR: 1.01 (95% CI: 0.98-1.04)]. This increased odds of OHCA occurred in both sexes. Finally, the ORs remained elevated when we repeated the analyses in individuals without registered ischaemic heart disease [OR: 1.36 (95% CI: 1.31-1.41)], without heart failure [OR: 1.33 (95% CI: 1.29-1.38)], or without any cardiovascular comorbidities [OR: 1.84 (95% CI: 1.70-2.00)]. Also, the OR remained elevated when H2-antagonists served as the reference group [OR: 1.28 (95% CI: 1.11-1.47)]. CONCLUSION:PPI use is associated with an increased risk of OHCA in the general population. Considering the widespread use of PPIs, this study raises concerns and the need for awareness to balance the benefit and risk of treatment.

Aim Conflicting results have been reported regarding the association between fluoroquinolones (FQs) and the risk of out-of-hospital cardiac arrest (OHCA). In particular, it has not become clear whether OHCA in FQ users is related to the inherent comorbidities or whether there is a direct pro-arrhythmic effect of FQs. Therefore, we studied the relation between FQs and OHCA in the general population.Methods Through Danish nationwide registries, we conducted a nested case–control study with OHCA cases of presumed cardiac causes and age/sex/OHCA date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the OR with 95% CI of OHCA comparing FQs with amoxicillin.Results The study population consisted of 46 578 OHCA cases (mean: 71 years (SD: 14.40), 68.8% men) and 232 890 matched controls. FQ was used by 276 cases and 328 controls and conferred no increase in the odds of OHCA compared with amoxicillin use after controlling for the relevant confounders (OR: 0.91 (95% CI: 0.71 to 1.16)). The OR of OHCA associated with FQ use did not vary significantly by age (OR≤65: 0.96 (95% CI: 0.53 to 1.74), OR>65: 0.88 (95% CI: 0.67 to 1.16), p value interaction=0.7818), sex (ORmen: 0.96 (95% CI: 0.70 to 1.31), ORwomen: 0.80 (95% CI: 0.53 to 1.20), p value interaction=0.9698) and pre-existing cardiovascular disease (ORabsent: 1.02 (95% CI: 0.57 to 1.82), ORpresent: 0.98 (95% CI: 0.75 to 1.28), p value interaction=0.3884), including heart failure (ORabsent: 0.93 (95% CI: 0.72 to 1.22), ORpresent: 1.11 (95% CI: 0.61 to 2.02), p value interaction=0.7083) and ischaemic heart disease (ORabsent: 0.85 (95% CI: 0.64 to 1.12), ORpresent: 1.38 (95% CI: 0.86 to 2.21), p value interaction=0.6230).Conclusion Our findings do not support an association between FQ exposure and OHCA in the general population. This lack of association was consistent in men and women, in all age categories, and in the presence or absence of cardiovascular disease.

ObjectivePatients with sleep apnea (SA) are at increased cardiovascular risk. However, little is known about the risk of out-of-hospital cardiac arrest (OHCA) in patients with SA. Therefore, we studied the relation between SA patients who did and did not receive continuous positive airway pressure (CPAP) therapy with OHCA in the general population.MethodsUsing nationwide databases, we conducted a nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date matched non-OHCA-controls from the general population. Conditional logistic regression models with adjustments for well-known OHCA risk factors were performed to generate odds ratio (OR) of OHCA comparing patients with SA receiving and not receiving CPAP therapy with individuals without SA.ResultsWe identified 46,578 OHCA-cases and 232,890 matched non-OHCA-controls [mean: 71 years, 68.8% men]. Compared to subjects without SA, having SA without CPAP therapy was associated with increased odds of OHCA after controlling for relevant confounders (OR:1.20, 95%-Cl:1.06-1.36), while having SA with CPAP therapy was not associated with OHCA (OR:1.04, 95%-Cl:0.93-1.36). Regardless of CPAP therapy, age and sex did not significantly influence our findings. Our findings were confirmed in: (I) patients with neither ischemic heart disease nor heart failure (untreated SA, OR:1.24, 95%-CI:1.04-1.47; SA with CPAP, OR:1.08, 95%-CI:0.93-1.25); and (II) in patients without cardiovascular disease (untreated SA, OR:1.33, 95%-CI:1.07-1.65; SA with CPAP, OR:1.14, 95%-CI:0.94-1.39).ConclusionSA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP.

AIMS:Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have a direct cardiac effect that is likely to be independent of its glucose lowering renal effect. Previous research has shown that SGLT2-is mitigate heart failure and prevent arrhythmic cardiac death. Our objective is to determine whether SGLT-2is reduce atrial fibrillation (AF) in comparison to other second-to third-line antidiabetic drugs in type 2 diabetes. METHODS AND RESULTS:We conducted a population-based, new-user active comparator cohort study using data from the UK Clinical Practice Research Datalink. We identified a cohort of patients initiating a new antidiabetic drug class between January 2013 and September 2020. This cohort included patients initiating their first ever non-insulin antidiabetic drug, as well as those who switched to or added-on an antidiabetic drug class not previously used in their treatment history. Individuals with a diagnosis of AF or atrial flutter at any time before cohort entry were excluded. Cox regression analysis with time-dependent covariates was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of AF comparing SGLT-2-is with other second-line to third-line antidiabetic drugs. Stratified analyses were performed according to sex, diabetes duration (<5 or ≥ 5 years), body mass index (BMI), HbA1c, and presence of heart failure.The cohort comprised 142 447 patients. SGLT-2is were associated with a statistically significant reduced hazard of AF compared to other second-line to third-line antidiabetic drugs (adjusted HR: 0.77 [95% CI: 0.68-0.88]). This reduced risk was present in both sexes but was more prominently among women (adjusted HRwomen: 0.60 [95% CI: 0.45-0.79]; HRmen: 0.85 [95% CI: 0.73-0.98]; P-value interaction: 0.012). There was no evidence for effect modification when stratifying on duration of diabetes, BMI, HbA1c, or presence of heart failure. CONCLUSION:SGLT-2is were associated with a reduced risk of AF in patients with type 2 diabetes compared to other second-line to third-line antidiabetic drugs. This reduced risk occurs in both sexes but more prominently among women.

Objective Patients with stress-related disorders and anxiety are at increased risk of developing cardiovascular disease. However, the risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We aimed to establish whether long-term stress (post-traumatic stress disorder, adjustment disorder) or anxiety is associated with OHCA in the general population. Methods We conducted a nested case–control study in a nationwide cohort of individuals between 1 June 2001 and 31 December 2015 in Denmark. Cases were OHCA patients with presumed cardiac causes. Each case was matched by age, sex and date of OHCA with 10 non-OHCA controls from the general population. HRs for OHCA were derived from Cox models after controlling for common OHCA risk factors. Stratified analyses were performed according to sex, age and pre-existing cardiovascular disease. Results We included 35 195 OHCAs and 351 950 matched controls (median age 72 years; 66.8% male). Long-term stress conditions were diagnosed in 324 (0.92%) OHCA cases and 1577 (0.45%) non-OHCA controls, and were associated with higher rate of OHCA (HR 1.44, 95% CI 1.27 to 1.64). Anxiety was diagnosed in 299 (0.85%) OHCA cases and 1298 (0.37%) controls, and was associated with increased rate of OHCA (HR 1.56, 95% CI1.37 to 1.79). We found no interaction with sex, age or history of cardiovascular diseases. Conclusion Patients with stress-related disorders or anxiety have an increased rate of OHCA. This association applies equally to men and women and is independent from the presence of cardiovascular disease. Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients.

Aim Methylphenidate, a sympathomimetic drug prescribed to treat attention-deficit/hyperactivity disorder (ADHD), is associated with cardiovascular events, but few studies have explored the risk of out-of-hospital cardiac arrest (OHCA). We investigated whether methylphenidate use is associated with OHCA in the general population. Methods and results Using Danish nationwide registries, we conducted a nested case-control study with OHCA cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the odds ratio (OR) of OHCA by comparing methylphenidate use with no use of methylphenidate. The study population consisted of 46 578 OHCA cases [median: 72 years (interquartile range: 62-81), 68.8% men] and 232 890 matched controls. Methylphenidate was used by 80 cases and 166 controls, and was associated with an increased OR of OHCA compared with non-users {OR: 1.78 [95% confidence interval (CI): 1.32-2.40]}. The OR was highest in recent starters (OR <= 180 days: 2.59, 95% CI: 1.28-5.23). The OR of OHCA associated with methylphenidate use did not vary significantly by age (P-value interaction: 0.37), sex (P-value interaction: 0.94), and pre-existing cardiovascular disease (P-value interaction: 0.27). Furthermore, the ORs remained elevated when we repeated the analyses in individuals without registered hospital-based ADHD (OR: 1.85, 95% CI: 1.34-2.55), without severe psychiatric disorders (OR: 1.98, 95% CI: 1.46-2.67), without depression (OR: 1.93, 95% CI: 1.40-2.65), or in non-users of QT-prolonging drugs (OR: 1.79, 95% CI: 1.27-2.54). Conclusion Methylphenidate use is associated with an increased risk of OHCA in the general population. This increased risk applies to both sexes and is independent of age and the presence of cardiovascular disease.

ObjectiveSarcoidosis is over-represented among victims of cardiac arrest. We aimed to establish whether sarcoidosis is associated with out-of-hospital cardiac arrest (OHCA) in the general population.MethodsWe conducted a nested case-control study in a nationwide cohort of individuals between 1 June 2001 and 31 December 2015 in Denmark. OHCA cases from presumed cardiac causes were matched 1:10 by sex and age on OHCA date with non-OHCA controls from the general population. The association between sarcoidosis and OHCA was assessed using Cox regression by calculating HR and 95% CIs. Models were adjusted for cardiovascular disease. Finally, stratified analyses were performed according to sex, heart failure and ischaemic heart disease. RESULTS: We identified 35 195 OHCA cases and 351 950 matched controls without OHCA (median age 72 years and 66.8% male). Patients with sarcoidosis had higher rate of OHCA compared with the general population after adjustments for common OHCA risk factors (HR 1.51, 95% CI 1.19 to 1.92). This increased OHCA rate occurred in women (HR 2.11, 95% CI 1.42 to 3.12) but not in men (HR 1.27, 95% CI 0.93 to 1.72; p value interaction=0.033), and was larger in patients with than without heart failure (HRheart failure: 2.59, 95% CI 1.42 to 4.73; HRno heart failure: 1.33, 95% CI 1.01 to 1.74; p value interaction: 0.007). The HR associated with sarcoidosis did not vary by the presence of ischaemic heart disease. CONCLUSION: Patients with sarcoidosis have a higher OHCA rate than the general population. This increased OHCA rate occurred in women but not in men, and was larger in patients with than without heart failure.

Aims We studied the effect of discontinuing beta-blockers following myocardial infarction in comparison to continuous beta-blocker use in optimally treated, stable patients without heart failure. Methods and results Using nationwide registers, we identified first-time myocardial infarction patients treated with beta-blockers following percutaneous coronary intervention or coronary angiography. The analysis was based on landmarks selected as 1, 2, 3, 4, and 5 years after the first redeemed beta-blocker prescription date. The outcomes included all-cause death, cardiovascular death, recurrent myocardial infarction, and a composite outcome of cardiovascular events and procedures. We used logistic regression and reported standardized absolute 5-year risks and risk differences at each landmark year. Among 21 220 first-time myocardial infarction patients, beta-blocker discontinuation was not associated with an increased risk of all-cause death, cardiovascular death, or recurrent myocardial infarction compared with patients continuing beta-blockers (landmark year 5; absolute risk difference [95% confidence interval]), correspondingly; -4.19% [-8.95%; 0.57%], -1.18% [-4.11%; 1.75%], and -0.37% [-4.56%; 3.82%]). Further, beta-blocker discontinuation within 2 years after myocardial infarction was associated with an increased risk of the composite outcome (landmark year 2; absolute risk [95% confidence interval] 19.87% [17.29%; 22.46%]) compared with continued beta-blocker use (landmark year 2; absolute risk [95% confidence interval] 17.10% [16.34%; 17.87%]), which yielded an absolute risk difference [95% confidence interval] at -2.8% [-5.4%; -0.1%], however, there was no risk difference associated with discontinuation hereafter. Conclusion Discontinuation of beta-blockers 1 year or later after a myocardial infarction without heart failure was not associated with increased serious adverse events.

Aim of the Database: The aim of the National Child Health Registry is to provide comprehensive insight into children's health and growth on a national scale by continuously monitoring the health status of Danish children. Through this effort, the registry assists the health authorities in prioritizing preventive efforts to promote better child health outcomes.Study Population: The registry includes all Danish children, however, incomplete coverage persists.Main Variables: The National Child Health Registry contains information on exposure to secondhand smoking, breastfeeding duration, and anthropometric measurements through childhood. The information in the registry is divided into three datasets: Smoking, Breastfeeding, and Measurements. Beside specific information on the three topics, all datasets include information on CPR-number, date of birth, sex, municipality, and region of residence. Database Status: The National Child Health Registry was established in 2009 and contains health information on children from all Danish municipalities, collected through routinely performed health examinations conducted by general practitioners and health nurses. Conclusion: The National Child Health Register is an asset to epidemiological and health research with nationwide information on children's health and growth in Denmark. Due to the unique Danish Civil Registration System, it is possible to link data from the National Child Health Register to information from several other national health and social registers which enables longitudinal unambiguous follow-up.

AIMS:Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are antidiabetic drugs that have beneficial direct effects on the myocardium by impacting cardiac ion channels and exchangers that control cardiac electrophysiology. We investigated the relationship between SGLT-2is in comparison to glucagon-like peptide-1 receptor agonists (GLP-1as) and out-of-hospital cardiac arrest (OHCA) in individuals with type 2 diabetes.METHODS:Using data from Danish registries, we conducted a nationwide nested case-control study in a cohort of individuals with type 2 diabetes between 2013 and 2019. Cases were defined as OHCA victims from presumed cardiac causes and each case was randomly matched with five controls without OHCA based on age, sex, and index-date (OHCA date). Conditional logistic regression models were used to estimate the adjusted odds ratios (ORs) with 95% confidence interval (95% CI) of OHCA comparing SGLT-2i use with GLP-1as (reference).RESULTS:The study population consisted of 3618 OHCA cases and 18 090 matched controls. SGLT-2i was used by 91 cases and 593 controls, and was associated with reduced odds of OHCA compared with use of GLP-1a after controlling for the relevant confounders (adjusted OR 0.76 [95% CI:0.58-0.99]). The adjusted OR of OHCA associated with SGLT-2i use did not vary significantly by sex (P-value interaction: 0.461), pre-existing cardiac disease (P-value interaction: 0.762), heart failure (P-value interaction: 0.891), diabetes duration (P-value interaction: 0.101), and chronic kidney disease (P-value interaction: 0.894).CONCLUSION:Use of SGLT-2i is associated with a reduced risk of OHCA compared with use of GLP-1a in type 2 diabetes.

AimsA few studies suggested that epilepsy and antiepileptic drugs with sodium channel‐blocking properties were independently associated with out‐of‐hospital cardiac arrest (OHCA). However, these findings have not yet been replicated.MethodsUsing Danish registries, we conducted a nested case–control study in a cohort of individuals between 1 June 2001 and 31 December 2015. Cases were defined as OHCA from presumed cardiac causes, and were matched with non‐OHCA‐controls based on sex, and age on the date of OHCA. Exposure of interest was epilepsy or antiepileptic drug use. To study the association between individual antiepileptic drug use and the rate of OHCA, we compared each antiepileptic drug with valproic acid. Cox regression with time‐dependent covariates was conducted to calculate hazard ratio (HR) and 95% confidence interval (CI).ResultsWe identified 35 195 OHCA‐cases and 351 950 matched non‐OHCA controls. Epilepsy (cases: 3.58%, controls: 1.60%) was associated with increased rate of OHCA compared with the general population (HR: 1.76, 95%CI: 1.64–1.88) when common OHCA risk factors were taken into account. When we studied antiepileptic drug use, we found that 2 antiepileptic drugs without sodium channel blockage, clonazepam (HR: 1.88, 95%CI: 1.45–2.44) and pregabalin (HR: 1.33, 95%CI: 1.05–1.69), were associated with OHCA, whereas none of the antiepileptic drugs with sodium channel blockage were associated with OHCA.ConclusionEpilepsy is associated with increased rate of OHCA. Our findings do not support a possible association between antiepileptic drugs with sodium channel‐blocking properties and OHCA.

Aim: To assess the risk of sudden cardiac arrest (SCA) associated with the use of carbamazepine (CBZ) and establish the possible underlying cellular electrophysiological mechanisms.Methods: The SCA risk association with CBZ was studied in general population cohorts using a case–control design (n = 5,473 SCA cases, 21,866 non-SCA controls). Effects of 1–100 µM CBZ on action potentials (APs) and individual membrane currents were determined in isolated rabbit and human cardiomyocytes using the patch clamp technique.Results: CBZ use was associated with increased risk of SCA compared with no use (adjusted odds ratio 1.90 [95% confidence interval: 1.12–3.24]). CBZ reduced the AP upstroke velocity of rabbit and human cardiomyocytes, without prominent changes in other AP parameters. The reduction occurred at ≥30 µM and was frequency-dependent with a more pronounced reduction at high stimulus frequencies. The cardiac sodium current (INa) was reduced at ≥30 μM; this was accompanied by a hyperpolarizing shift in the voltage-dependency of inactivation. The recovery from inactivation was slower, which is consistent with the more pronounced AP upstroke velocity reduction at high stimulus frequencies. The main cardiac K+ and Ca2+ currents were unaffected, except reduction of L-type Ca2+ current by 100 µM CBZ.Conclusion: CBZ use is associated with an increased risk of SCA in the general population. At concentrations of 30 µM and above, CBZ reduces AP upstroke velocity and INa in cardiomyocytes. Since the concentration of 30 µM is well within the therapeutic range (20–40 µM), we conclude that CBZ increases the risk of SCA by a reduction of the cardiac INa.

Depolarization-blocking drugs (DB drugs) used for cardiac disease increase the risk of cardiac arrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) and out-of-hospital cardiac arrest (OHCA) in specific patient groups. However, it is unknown whether drugs for non-cardiac disease that block cardiac depolarization as the off-target effect increase the risk of OHCA on a population level. Therefore, we aimed to investigate OHCA risk of non-cardiac, DB drugs in the community. We conducted a population-based case-control study. We included OHCA cases from an emergency-medical-services-attended OHCA registry in the Netherlands (ARREST:2009–2018), and age/sex/OHCA-date matched non-OHCA controls. We calculated adjusted odds ratios (ORadj) of use of non-cardiac DB drugs for OHCA using conditional logistic regression. Stratified analyses were performed according to first-registered rhythm (VT/VF or non-VT/VF), sex, and age (≤50, 50–70, or ≥70 years). We included 5473 OHCA cases of whom 427 (7.8%) used non-cardiac, DB drugs and 21,866 non-OHCA controls of whom 835 (3.8%) used non-cardiac, DB drugs and found that non-cardiac, DB-drug use was associated with increased OHCA-risk when compared to no use (ORadj1.6[95%-CI:1.4–1.9]). Stratification by first-recorded rhythm revealed that this applied to OHCA with non-VT/VF (asystole) (ORadj2.5[95%-CI:2.1–3.0]) but not with VT/VF (ORadj1.0[95%-CI:0.8–1.2]; p-value interaction < 0.001). The risk was higher in women (ORadj1.8[95%-CI:1.5–2.2] than in men (ORadj1.5[95%-CI:1.2–1.8]; p-value interaction = 0.030) and at younger ages (ORadj≥70yrs1.4[95%-CI:1.2–1.7]; ORadj50–70yrs1.7[95%-CI:1.4–2.1]; ORadj≤50yrs3.2[95%-CI:2.1–5.0]; p-value interaction < 0.001). Use of non-cardiac, DB drugs is associated with increased OHCA risk. This increased risk occurred in patients in whom non-VT/VF was the first-registered rhythm, and it occurred in both sexes but more prominently among women and more strongly in younger patients (≤50 years).

Aims Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are antidiabetic agents that can have direct cardiac effects by impacting on cardiac ion transport mechanisms that control cardiac electrophysiology. We studied the association between SGLT-2i use and all-cause mortality and the risk of sudden cardiac arrest (SCA) in patients with type 2 diabetes. Methods Using data from the UK Clinical Practice Research Datalink, a cohort study among patients initiating a new antidiabetic drug class on or after January 2013 through September 2020 was conducted. A Cox regression with time-dependent covariates was performed to estimate the hazard ratios (HRs) of SCA and all-cause mortality comparing SGLT-2is with other second- to third-line antidiabetic drugs. Stratified analyses were performed according to sex, diabetes duration (<5 or >= 5 years), and the presence of cardiovascular disease. Results A total of 152 591 patients were included. Use of SGLT-2i was associated with a reduced HR of SCA when compared with other second- to third-line antidiabetic drugs after adjustment for common SCA risk factors, although this association marginally failed to reach statistical significance [HR: 0.62, 95% confidence interval (95% CI): 0.38-1.01]. The HR of all-cause mortality associated with SGLT-2i use when compared with other second- to third-line antidiabetics was 0.43 (95% CI: 0.39-0.48) and did not vary by sex, diabetes duration, or the presence of cardiovascular disease. SGLT-2i use remained associated with lower all-cause mortality in patients without concomitant insulin use (HR: 0.56, 95% CI: 0.50-0.63). Conclusion SGLT-2i use was associated with reduced all-cause mortality in patients with type 2 diabetes. The association between use of SGLT-2i and reduced risk of SCA was not statistically significant.

Aim Activated blood platelet products facilitate myocardial intracellular Ca2+ overload, thereby provoking afterdepolarizations and increasing susceptibility of ischemic myocardium to ventricular fibrillation (VF). These effects are counteracted in vitro by acetylsalicylic acid (ASA), but no prior study investigated whether ASA is associated with decreased out-of-hospital cardiac arrest (OHCA) risk on a population level. Therefore, we studied whether ASA and other antiplatelet drugs (carbasalate calcium, clopidogrel) are associated with decreased risk of OHCA. Methods We conducted a population-based case-control study among individuals (772 OHCA-cases with documented VT/VF, 2444 non-OHCA-controls) who had used antiplatelet drugs in the year before index-date (OHCA-date), and studied the association between current antiplatelet drug use and OHCA-risk with multivariable logistic regression analysis. Results ASA use was associated with reduced OHCA-risk (adjusted odds ratio (ORadj) 0.6 [0.5–0.8]), and more so in women (ORadj 0.3 [0.2–0.6]) than in men (ORadj 0.7 [0.5–0.95], Pinteraction 0.021). Carbasalate calcium was associated with decreased OHCA-risk in women (ORadj 0.5 [0.3–0.9]), but not in men (ORadj 1.3 [0.96–1.7], Pinteraction 0.005). Clopidogrel was not associated with reduction in OHCA-risk. Risk reduction associated with ASA in patients with OHCA was similar in the presence of acute myocardial infarction (AMI) (ORadj 0.6 [0.4–0.9]) and in the absence of AMI (ORadj 0.7 [0.4–1.2]). Conclusion ASA use was associated with reduced OHCA-risk in both sexes, and more so in women, while carbasalate calcium only protected women. Clopidogrel was not associated with reduced OHCA-risk.

Aim Inflammatory cytokines in patients with rheumatoid arthritis (RA) directly affect cardiac electrophysiology by inhibiting cardiac potassium currents, leading to delay of cardiac repolarisation and QT-prolongation. This may result in lethal arrhythmias. We studied whether RA increases the rate of out-of-hospital cardiac arrest (OHCA) in the general population. Methods We conducted a nested case–control in a cohort of individuals between 1 June 2001 and 31 December 2015. Cases were OHCA patients from presumed cardiac causes, and were matched with non-OHCA-controls based on age, sex and OHCA date. Cox-regression with time-dependent covariates was conducted to assess the association between RA and OHCA by calculating the HR and 95% CI. Stratified analyses were performed according to sex and presence of cardiovascular diseases. Also, the association between OHCA and use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with RA was studied. Results We included 35 195 OHCA cases of whom 512 (1.45%) had RA, and 351 950 non-OHCA controls of whom 3867 (1.10%) had RA. We found that RA was associated with increased rate of OHCA after adjustment for cardiovascular comorbidities and use of QT-prolonging drugs (HR: 1.22, 95% CI: 1.11 to 1.34). Stratification by sex revealed that increased OHCA rate occurred in women (HR: 1.32, 95% CI: 1.16 to 1.50) but not in men (HR: 1.12, 95% CI: 0.97 to 1.28; P value interaction=0.046). OHCA rate of RA was not further increased in patients with cardiovascular disease. Finally, in patients with RA, use of NSAIDs was not associated with OHCA. Conclusion In the general population, RA is associated with increased rate of OHCA in women but not in men.