Sodium-glucose cotransporter-2 inhibitors and the risk of atrial fibrillation in patients with type 2 diabetes: a population-based cohort study.

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.

Use of proton pump inhibitors is associated with increased risk of out-of-hospital cardiac arrest in the general population: a nested case-control study.

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.

Fluoroquinolones do not provide added risk of out-of-hospital cardiac arrest: a nationwide study.

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.

Association between long-term statin use and cataract surgery: a nationwide study on 505 105 cataract surgery patients.

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.

Sleep apnea, the risk of out-of-hospital cardiac arrest, and potential benefits of continuous positive airway pressure therapy: A nationwide study.

OBJECTIVE: Patients 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. METHODS: Using 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. RESULTS: We 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). CONCLUSION: SA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP.