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Cardiovascular medications used for comorbid diseases in patients with atrial fibrillation. The JoFib study

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Abstract

Purpose

Many atrial fibrillation (AF) patients use cardiovascular medications for indications other than AF. These medications can affect morbidity and mortality. We aim to investigate the characteristics of AF patients who use different medication classes and their clinical course.

Methods

We collected data from the prospective, multicenter registry, JoFib study. We identified classes of non-AF medications (medications not used for rate control, rhythm control, or anticoagulation), described demographic and clinical characteristics, and investigated AF-related outcomes according to these medication classes.

Results

From a total of 2020 patients, five classes of cardiovascular non-AF medications were identified, aspirin, P2Y12 inhibitors, ACE inhibitors/ARBs, statins, and diuretics. The most commonly used non-AF medications were diuretics and ACE inhibitors/ARBs (39.2%, and 39%, respectively). 51% of AF patients took more than one non-AF medication. Multivariable Cox regression analysis demonstrated that ACE inhibitor/ARB therapy independently reduced the risks of all-cause mortality and cardiovascular mortality (aHR 0.50, 95%CI 0.37–0.68; aHR 0.51, 95%CI 0.34–0.75, respectively) and that statin therapy reduced the risk of cardiovascular mortality (aHR 0.68, 95%CI 0.48–0.98) in AF patients. Multivariable logistic regression analysis demonstrated a protective effect of statin therapy against the secondary outcome, clinically relevant non-major bleeding (CRNMB) (adjusted OR 0.62 95%CI 0.42–0.94).

Conclusion

Our findings suggest a protective effect of ACE inhibitors/ARBs against all-cause and cardiovascular mortality, statins against cardiovascular mortality, and CRNMB in patients with AF. Accordingly, these medications should be encouraged in patients with AF when indicated. Additionally, future research should explore whether these medications should be offered to AF patients more routinely. The study was registered with Clinicaltrials.gov (unique identifier number: NCT03917992, Registration date:14/4/2019).

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Kornej J, Börschel CS, Benjamin EJ, Schnabel RB (2020) Epidemiology of Atrial Fibrillation in the 21st Century. Circ Res 127:4–20. https://doi.org/10.1161/CIRCRESAHA.120.316340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tsao CW, Aday AW, Almarzooq ZI et al (2023) Heart Disease and Stroke Statistics—2023 update: a Report from the American Heart Association. Circulation 147:e93–e621. https://doi.org/10.1161/CIR.0000000000001123

    Article  PubMed  Google Scholar 

  3. January CT, Wann LS, Calkins H et al (2019) 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS Guideline for the management of patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines and the heart R. J Am Coll Cardiol 74:104–132.https://doi.org/10.1016/j.jacc.2019.01.011

    Article  PubMed  Google Scholar 

  4. Park CS, Kim B, Rhee T-M et al (2023) Association between renin–angiotensin–aldosterone system blockade and clinical outcomes in patients with hypertension: real-world observation from a nationwide hypertension cohort. Clin Res Cardiol 112:1577–1586. https://doi.org/10.1007/s00392-023-02179-3

    Article  CAS  PubMed  Google Scholar 

  5. Yu Z, Zhang D, Ji Q, Yi F (2021) Inhibition of the renin-angiotensin-aldosterone system prevents and cures atrial fibrillation: an overview of systematic reviews. Med (Baltim) 100

  6. Imazio M (2012) Primary Prevention of Atrial Fibrillation where are we in 2012? J Atr Fibrillation 5:608.https://doi.org/10.4022/jafib.608

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mascolo A, Urbanek K, De Angelis A et al (2020) Angiotensin II and angiotensin 1–7: which is their role in atrial fibrillation? Heart Fail Rev 25:367–380. https://doi.org/10.1007/s10741-019-09837-7

    Article  PubMed  Google Scholar 

  8. Hindricks G, Potpara T, Dagres N et al (2021) 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 42:373–498. https://doi.org/10.1093/EURHEARTJ/EHAA612

    Article  PubMed  Google Scholar 

  9. Oraii A, Vasheghani-Farahani A, Oraii S et al (2021) Update on the efficacy of statins in primary and secondary prevention of atrial fibrillation. Rev Port Cardiol 40:509–518. https://doi.org/10.1016/j.repc.2020.11.010

    Article  PubMed  Google Scholar 

  10. Hammoudeh AJ, Khader Y, Kadri N et al (2021) Adherence to the 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS Guideline on the use of oral anticoagulant agents in Middle Eastern patients with Atrial Fibrillation: the Jordan Atrial Fibrillation (JoFib) Study. Int J Vasc Med 2021(5515089). https://doi.org/10.1155/2021/5515089

  11. Heidenreich PA, Bozkurt B, Aguilar D et al (2022) 2022 AHA/ACC/HFSA Guideline for the management of Heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice guidelines. Circulation 145:e895–e1032. https://doi.org/10.1161/CIR.0000000000001063

    Article  PubMed  Google Scholar 

  12. Byrne RA, Rossello X, Coughlan JJ et al (2023) 2023 ESC guidelines for the management of acute coronary syndromes: developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J 44:3720–3826. https://doi.org/10.1093/eurheartj/ehad191

    Article  CAS  PubMed  Google Scholar 

  13. Xu W, Yang Y, Zhu J et al (2022) Impact of renin–angiotensin–aldosterone-system inhibitor drugs on mortality in patients with atrial fibrillation and hypertension. BMC Cardiovasc Disord 22:141. https://doi.org/10.1186/s12872-022-02580-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wachtell K, Lehto M, Gerdts E et al (2005) Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan intervention for end point reduction in hypertension (LIFE) study. J Am Coll Cardiol 45:712–719. https://doi.org/10.1016/j.jacc.2004.10.068

    Article  CAS  PubMed  Google Scholar 

  15. Menichelli D, Poli D, Antonucci E et al (2024) Renin-angiotensin-aldosterone system inhibitors and mortality risk in elderly patients with atrial fibrillation. Insights from the nationwide START registry. Eur J Intern Med 119:84–92. https://doi.org/10.1016/j.ejim.2023.08.019

    Article  CAS  PubMed  Google Scholar 

  16. Lip GYH, Frison L, Grind M, Committee on B of the SI and the SES (2007) Angiotensin converting enzyme inhibitor and angiotensin receptor blockade use in relation to outcomes in anticoagulated patients with atrial fibrillation. J Intern Med 261:577–586. https://doi.org/10.1111/j.1365-2796.2007.01780.x

    Article  CAS  PubMed  Google Scholar 

  17. Amarenco P, Labreuche J (2009) Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 8:453–463. https://doi.org/10.1016/S1474-4422(09]70058-4

    Article  CAS  PubMed  Google Scholar 

  18. Choi KH, Seo WK, Park MS et al (2019) Effect of Statin Therapy on Outcomes of Patients With Acute Ischemic Stroke and Atrial Fibrillation. J Am Heart Assoc. 2019;8[24]:e013941. EpubDec 12:. https://doi.org/10.1161/JAHA.119.013941

  19. Pastori D, Baratta F, Di Rocco A et al (2021) Statin use and mortality in atrial fibrillation: a systematic review and meta-analysis of 100,287 patients. Pharmacol Res 165:105418. https://doi.org/10.1016/j.phrs.2021.105418

    Article  CAS  PubMed  Google Scholar 

  20. Goldstein LB, Amarenco P, Szarek M et al (2008) Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology 70:2364 LP – 2370. https://doi.org/10.1212/01.wnl.0000296277.63350.77

  21. Proietti M, Laroche C, Nyvad O et al (2017) Use of statins and adverse outcomes in patients with atrial fibrillation: an analysis from the EURObservational Research Programme Atrial Fibrillation (EORP-AF) general registry pilot phase. Int J Cardiol 248:166–172. https://doi.org/10.1016/j.ijcard.2017.08.055

    Article  PubMed  Google Scholar 

  22. Odutayo A, Wong CX, Hsiao AJ et al (2016) Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis. BMJ 354:i4482. https://doi.org/10.1136/bmj.i4482

    Article  PubMed  Google Scholar 

  23. Zakeri R, Morgan AD, Sundaram V et al (2021) Under-recognition of heart failure in patients with atrial fibrillation and the impact of gender: a UK population-based cohort study. BMC Med 19:179. https://doi.org/10.1186/s12916-021-02048-8

    Article  PubMed  PubMed Central  Google Scholar 

  24. Shengbo Y (2011) Diuretics administration correlate with atrial fibrillation in patients with chronic systolic heart failure. Heart 97.https://doi.org/10.1136/heartjnl-2011-300867.625. A213 LP-A213

  25. Hamon M, Lemesle G, Tricot O et al (2014) Incidence, source, determinants, and prognostic impact of major bleeding in outpatients with stable coronary artery disease. J Am Coll Cardiol 64:1430–1436. https://doi.org/10.1016/j.jacc.2014.07.957

    Article  PubMed  Google Scholar 

  26. Lamberts M, Gislason GH, Lip GYH et al (2014) Antiplatelet Therapy for stable coronary artery disease in Atrial Fibrillation patients taking an oral anticoagulant. Circulation 129:1577–1585. https://doi.org/10.1161/CIRCULATIONAHA.113.004834

    Article  CAS  PubMed  Google Scholar 

  27. Lemesle G, Ducrocq G, Elbez Y et al (2017) Vitamin K antagonists with or without long-term antiplatelet therapy in outpatients with stable coronary artery disease and atrial fibrillation: Association with ischemic and bleeding events. Clin Cardiol 40:932–939. https://doi.org/10.1002/clc.22750

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

No funds, grants, or other support was received.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan

    Nasr Alrabadi & Lama Alburie

  2. Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Mohammed Al-Nusair & Mohamad Aljarrah

  3. Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jadara University, Irbid, Jordan

    Razan Haddad

  4. Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

    Nizar Mhaidat

  5. Department of Cardiology, Istishari Hospital, Amman, Jordan

    Ayman Hamoudeh

Authors
  1. Nasr Alrabadi
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  2. Mohammed Al-Nusair
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  4. Lama Alburie
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  7. Ayman Hamoudeh
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by [Nasr Alrabadi, Mohammed Al-Nusair, and Lama Alburie]. The first draft of the manuscript was written by [Nasr Alrabadi, Mohammed Al-Nusair, and Razan Haddad] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Nasr Alrabadi.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board (IRB) of participating centers (16072019151). The study was registered with Clinicaltrials.gov (unique identifier number: NCT03917992).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

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228_2024_3622_MOESM1_ESM.pdf

Supplementary Material 1: Supplementary Tables 1–13 which further describe sociodemographic and clinical characteristics of patients with AF according to medications used for comorbid diseases and Figures S1-S5 which present forest plots with adjusted HRs and 95% CIs for AF-related outcomes according to non-AF medications.

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Alrabadi, N., Al-Nusair, M., Haddad, R. et al. Cardiovascular medications used for comorbid diseases in patients with atrial fibrillation. The JoFib study. Eur J Clin Pharmacol 80, 545–552 (2024). https://doi.org/10.1007/s00228-024-03622-8

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  • DOI: https://doi.org/10.1007/s00228-024-03622-8

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