Correct Dosing, Adherence and Persistence of DOACs in Atrial Fibrillation and Chronic Kidney Disease: a Systematic Review and Meta-analysis

Overview

Journal Open Heart

Publisher BMJ Publishing Group

Specialty Cardiology & Vascular Diseases

Date 2023 Jul 7

PMID 37419525

Authors

Subo Emanuel

Riyaz A Kaba

Gayathri Delanerolle

Benjamin C T Field

Gregory Y H Lip

Simon de Lusignan

Affiliations

Soon will be listed here.

Abstract

Background: Chronic kidney disease (CKD) and atrial fibrillation (AF) are increasing in prevalence globally and share common risk factors.Our aim was to characterise real-world evidence on direct oral anticoagulant (DOAC) prescribing for people with AF and CKD, in terms of adherence, persistence and renal dose titration.

Methods: PubMed, EMBASE and CINAHL were searched from inception to June 2022. Our search terms included a combination of Medical Subject Headings (MeSH) terms and keywords including 'atrial fibrillation', 'chronic kidney disease', 'adherence', 'persistence', 'direct oral anticoagulants' and 'dosing'. Data extraction and quality assessment were undertaken by two reviewers independently. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Age, sex, diabetes, hypertension and heart failure were chosen as variables of interest.

Results: From 19 studies, a total of 252 117 patients were included with CKD and AF. Meta-analysis was only possible in seven studies with 128 406 patients, five on DOAC dose titration and two on adherence. There were insufficient studies on persistence. Our meta-analysis of dosing showed that 68% of patients with CKD and AF had correct dosing. There was no evidence to show any association between correct DOAC dosing and variables of interest. Overall, 67% of patients were DOAC adherent.

Conclusion: Adherence and correct dosing of DOACs were suboptimal compared with other medications in the pooled studies with respect to CKD and AF. Thus, further research is required as the lack of generalisation of findings is a rate-limiting factor for improved DOAC management in AF and CKD.

Prospero Registration Number: CRD;42022344491.

Citing Articles

Renal function and adverse clinical events in anticoagulated patients with atrial fibrillation: insights from the GLORIA-AF Registry Phase III.

Liu Y, Lam S, Romiti G, Huang B, Chen Y, Chao T J Thromb Thrombolysis. 2025; 58(2):165-177.

PMID: 39924624 PMC: 11885355. DOI: 10.1007/s11239-025-03067-5.

Anticoagulation in Patients with Chronic Kidney Disease.

Elenjickal E, Travlos C, Marques P, Mavrakanas T Am J Nephrol. 2023; 55(2):146-164.

PMID: 38035566 PMC: 10994631. DOI: 10.1159/000535546.

References

Jackson 2nd L, Schrader P, Thomas L, Steinberg B, Blanco R, Allen L . Dosing of Direct Oral Anticoagulants in Patients with Moderate Chronic Kidney Disease in US Clinical Practice: Results from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF II). Am J Cardiovasc Drugs. 2021; 21(5):553-561. DOI: 10.1007/s40256-021-00473-x. View

Yeo S, Toh M, Lee S, Seet R, Wong L, Yau W . Impact of medication nonadherence on stroke recurrence and mortality in patients after first-ever ischemic stroke: Insights from registry data in Singapore. Pharmacoepidemiol Drug Saf. 2020; 29(5):538-549. DOI: 10.1002/pds.4981. View

Cho M, Yun J, Park J, Kim Y, Lee J, Kim H . Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients With Atrial Fibrillation. Stroke. 2018; 50(1):110-118. DOI: 10.1161/STROKEAHA.118.023093. View

Ocak G, Khairoun M, Khairoun O, Bos W, Fu E, Cramer M . Chronic kidney disease and atrial fibrillation: A dangerous combination. PLoS One. 2022; 17(4):e0266046. PMC: 8989340. DOI: 10.1371/journal.pone.0266046. View

Piccini J, Xu H, Cox M, Matsouaka R, Fonarow G, Butler J . Adherence to Guideline-Directed Stroke Prevention Therapy for Atrial Fibrillation Is Achievable. Circulation. 2019; 139(12):1497-1506. DOI: 10.1161/CIRCULATIONAHA.118.035909. View

Stroup D, Berlin J, Morton S, Olkin I, Williamson G, Rennie D . Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000; 283(15):2008-12. DOI: 10.1001/jama.283.15.2008. View

Pages A, Sabatier R, Sallerin B . Factors Associated With the Choice of Oral Anticoagulant Class in the Older Patients: An Observational Study. J Cardiovasc Pharmacol Ther. 2020; 25(4):332-337. DOI: 10.1177/1074248420917811. View

Shore S, Carey E, Turakhia M, Jackevicius C, Cunningham F, Pilote L . Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the veterans health administration. Am Heart J. 2014; 167(6):810-7. PMC: 5381802. DOI: 10.1016/j.ahj.2014.03.023. View

Cataldo N, Pegoraro V, Ripellino C, Bertasi V, Di Turi R, Pastorello M . Non-persistence risk and health care resource utilization of Italian patients with non-valvular atrial fibrillation. Recenti Prog Med. 2018; 109(2):113-121. DOI: 10.1701/2865.28904. View

10.

Maura G, Pariente A, Alla F, Billionnet C . Adherence with direct oral anticoagulants in nonvalvular atrial fibrillation new users and associated factors: a French nationwide cohort study. Pharmacoepidemiol Drug Saf. 2017; 26(11):1367-1377. PMC: 5697683. DOI: 10.1002/pds.4268. View

11.

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

12.

Dhamane A, Hernandez I, Di Fusco M, Gutierrez C, Ferri M, Russ C . Non-persistence to Oral Anticoagulation Treatment in Patients with Non-valvular Atrial Fibrillation in the USA. Am J Cardiovasc Drugs. 2021; 22(3):333-343. PMC: 9061668. DOI: 10.1007/s40256-021-00501-w. View

13.

Guo Y, Kotalczyk A, Imberti J, Wang Y, Lip G . Poor adherence to guideline-directed anticoagulation in elderly Chinese patients with atrial fibrillation: a report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry. Eur Heart J Qual Care Clin Outcomes. 2021; 9(2):169-176. PMC: 9972510. DOI: 10.1093/ehjqcco/qcab054. View

14.

Briasoulis A, Gao Y, Inampudi C, Alvarez P, Asleh R, Chrischilles E . Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses. BMC Cardiovasc Disord. 2020; 20(1):42. PMC: 6998084. DOI: 10.1186/s12872-020-01340-4. View

15.

Joy M, Williams J, Emanuel S, Kar D, Fan X, Delanerolle G . Trends in direct oral anticoagulant (DOAC) prescribing in English primary care (2014-2019). Heart. 2022; 109(3):195-201. DOI: 10.1136/heartjnl-2022-321377. View

16.

Rhee T, Lee S, Choi E, Oh S, Lip G . Efficacy and Safety of Oral Anticoagulants for Atrial Fibrillation Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2022; 9:885548. PMC: 9226375. DOI: 10.3389/fcvm.2022.885548. View

17.

Ting C, Rhoten M, Dempsey J, Nichols H, Fanikos J, Ruff C . Evaluation of Direct Oral Anticoagulant Prescribing in Patients With Moderate to Severe Renal Impairment. Clin Appl Thromb Hemost. 2021; 27:1076029620987900. PMC: 7863154. DOI: 10.1177/1076029620987900. View

18.

Kovesdy C . Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022; 12(1):7-11. PMC: 9073222. DOI: 10.1016/j.kisu.2021.11.003. View

19.

Balduzzi S, Rucker G, Schwarzer G . How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health. 2019; 22(4):153-160. PMC: 10231495. DOI: 10.1136/ebmental-2019-300117. View

20.

Erdogan T, Erdogan O, Ozturk S, Oren M, Karan M, Bahat G . Non-vitamin K antagonist oral anticoagulant use at doses inappropriately lower than recommended in outpatient older adults: a real-life data. Eur Geriatr Med. 2021; 12(4):809-816. DOI: 10.1007/s41999-021-00452-0. View