Effect of long-term beta-blocker treatment following myocardial infarction among stable, optimally treated patients without heart failure in the reperfusion era: a Danish, nationwide cohort study

Holt, Anders; Blanche, Paul; Zareini, Bochra; Rajan, Deepthi; El-Sheikh, Mohammed; Schjerning, Anne-Marie; Schou, Morten; Torp‐Pedersen, Christian; McGettigan, Patricia; Gislason, Gunnar; Lamberts, Morten

doi:10.1093/eurheartj/ehaa1058

Cited by 49 publications

(31 citation statements)

References 22 publications

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“…The mechanism is unclear. However, one might speculate that inhibiting sympathetic nervous system with beta‐blocker might result in decreased heart rate and cardiac workload, 30 which in turn helps preserve cardiac function. Further studies are needed to corroborate the current findings.…”

Section: Discussionmentioning

confidence: 99%

Association between lipoprotein (a) and heart failure with reduced ejection fraction development

Zhang

Long

et al. 2021

Clinical Laboratory Analysis

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Background The current study aimed to evaluate the relationship between baseline serum lipoprotein (a) [Lp(a)] level and heart failure with reduced ejection fraction (HFrEF) development. Methods This was a retrospective study, and participants were enrolled from the outpatient clinic. All data were extracted from the electronic health record of the outpatient clinic system. The follow‐up was performed through reviewing the clinical notes at the outpatient clinic system, and study outcome of the current study was the first diagnosis of HFrEF. Participants were divided into low Lp(a) (<30 mg/dl, n = 336) and high Lp(a) (≥30 mg/dl, n = 584) groups. Results Individuals in the high Lp(a) group were more likely to be men and have diabetes mellitus (DM) and dyslipidemia. Increased Lp(a) at baseline was positively associated with serum N‐terminal pro‐B natriuretic peptide level while negatively associated with left ventricular ejection fraction (LVEF) at follow‐up. After adjusting for covariates, per 10 mg/dl increase in baseline Lp(a) remained significantly associated with HFrEF, with odds ratio of 1.17 (95% confidence interval of 1.05, 1.46). The magnitude of association between baseline Lp(a) level and HFrEF was greater in men and in individuals with DM or coronary heart disease (CHD), while it was weaker in individuals treated with beta‐blocker at baseline. Conclusion Increased Lp(a) at baseline was associated with HFrEF development. The adverse effects of Lp(a) were greater on men and individuals with DM or CHD, which were mitigated by beta‐blocker therapy. These findings together underscore the possibility and usefulness of Lp(a) as a new risk factor to predict HFrEF.

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Section: Discussionmentioning

confidence: 99%

Association between lipoprotein (a) and heart failure with reduced ejection fraction development

Zhang

Long

et al. 2021

Clinical Laboratory Analysis

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“…This study was based on nationwide, Danish administrative health registers previously used by this group. [15][16][17][18] Please see Appendix (available online) for details.…”

Section: Methods and Materials Data Sourcesmentioning

confidence: 99%

Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran

Holt

Strange

Rasmussen

et al. 2022

The American Journal of Medicine

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BACKGROUND: Bleeding safety in relation to use of systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban, or dabigatran is insufficiently explored, despite clinical relevance and several reports suggesting associations. METHODS: Using nationwide Danish registers, we identified patients with atrial fibrillation initiated on apixaban, rivaroxaban, or dabigatran from 2012-2018. We investigated associations between bleeding incidents and systemic fluconazole or topical azole treatment using a case-crossover design with 30-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We included 32,340 (36%), 32,409 (36%), and 24,940 (28%) patients initiated on apixaban, rivaroxaban, and dabigatran, respectively. Patients on apixaban were older (median age: 77 years; interquartile range [IQR] 70-84) compared with rivaroxaban users (median age: 75 years; IQR 68-82) and patients on dabigatran (median age: 73 years; IQR 66-80). Apixaban users had a significantly increased risk of bleeding following exposure to systemic fluconazole: odds ratio (OR) 3.5; 95% confidence interval (CI), 1.4-10.6. No increased risk was found among rivaroxaban and dabigatran users: ORs of 0.9 (95% CI, 0.2-3.0) and 1.7 (95% CI, 0.5-5.6), respectively. As to bleeding risk pertaining to topical azole exposure among apixaban, rivaroxaban, and dabigatran users, no association was found, with corresponding ORs of 0.8 (95% CI, 0.5-1.3); 1.3 (95% CI, 0.9-2.1); and 1.2 (95% CI 0.8-1.8), respectively. CONCLUSION: In patients with atrial fibrillation on either apixaban, rivaroxaban, or dabigatran, an association between an elevated bleeding risk and use of systemic fluconazole was found among patients on apixaban. We found no increased risk of bleeding following co-exposure to topical azoles.

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“…This study was based on nationwide, Danish registers. These are well described and previously used by this research group 6–9. Please see online supplemental appendix for details.…”

Section: Methodsmentioning

confidence: 99%

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants

Holt

Blanche

Zareini

et al. 2021

Heart

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ObjectiveGastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.MethodsThis is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012–2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case–control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.Results98 376 patients on NOACs (median age: 75 years (IQR: 68–82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).ConclusionsConcomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

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Effect of long-term beta-blocker treatment following myocardial infarction among stable, optimally treated patients without heart failure in the reperfusion era: a Danish, nationwide cohort study

Cited by 49 publications

References 22 publications

Association between lipoprotein (a) and heart failure with reduced ejection fraction development

Association between lipoprotein (a) and heart failure with reduced ejection fraction development

Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants

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