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Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis

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Abstract

Background

In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference.

We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT).

Methods

A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel–Haenszel method.

Results

Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36–2.63]).

Conclusions

In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.

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Abbreviations

AF:

Atrial fibrillation

DOAC:

Direct oral anticoagulation

OAC:

Oral anticoagulation

VKA:

Vitamin K antagonist

SAPT:

Single antiplatelet therapy

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Funding

This work was supported by an Education Research Grant from Academy of Teaching Scholars University of Oklahoma College of Medicine awarded to Zain Ul Abideen Asad, MD MS.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Oklahoma Health Sciences Center, 800 Stanton L. Young Blvd, AAT 5400, Oklahoma City, OK, 73104, USA

    Aamina Shakir, Arsalan Khan, Siddharth Agarwal, Warren M. Jackman, Stavros Stavrakis & Zain Ul Abideen Asad

  2. Robert M Bird Health Sciences Library, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Shari Clifton

  3. Department of Biostatistics and Epidemiology, Hudson College of Public Health, Oklahoma City, OK, USA

    Jessica Reese

  4. Section of Electrophysiology, Division of Cardiology, University of California Davis, Sacramento, CA, USA

    Muhammad Bilal Munir

  5. Baystate Medical Center, Springfield, MA, USA

    Usama Bin Nasir

  6. Houston Methodist Hospital, Houston, TX, USA

    Safi U. Khan

  7. Kansas City Heart Rhythm Institute, Overland Park, MO, USA

    Rakesh Gopinathannair

  8. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA

    Christopher V. DeSimone & Abhishek Deshmukh

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  1. Aamina Shakir
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Shakir, A., Khan, A., Agarwal, S. et al. Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis. J Interv Card Electrophysiol 66, 493–506 (2023). https://doi.org/10.1007/s10840-022-01347-1

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