Heart Failure Treatment and Management · Journal article

Safety and efficacy of DOACs in clinically complex phenotypes of patients with atrial fibrillation: focus on frailty, multimorbidity and polypharmacy

Expert Opinion on Drug Safety · July 11, 2026

Expert Guidance Why this matters to you Expert discussion

A consensus or society position rather than new primary data.

AI Summary

This narrative review concludes that DOACs are safe and effective in complex AF patients (frail, multimorbid, or on polypharmacy) when individualised according to frailty status, renal function, and medication review. The evidence derives from trials and observational studies, with DOACs showing similar or superior outcomes versus warfarin. The authors recommend frailty screening and structured polypharmacy review as implementation strategies.

What was studied

Narrative review. Atrial fibrillation patients with frailty, multimorbidity, and/or polypharmacy—populations underrepresented in randomised clinical trials.. Intervention: Direct oral anticoagulants (DOACs). Compared with: Vitamin K antagonists (warfarin) and other anticoagulation strategies.

Key findings

DOACs demonstrate similar or superior efficacy and safety compared with vitamin K antagonists in frail and multimorbid patients DOACs are associated with fewer drug-drug interactions and simplified dosing strategies compared with other anticoagulants Observational data support real-world effectiveness of DOACs when treatment is individualised according to frailty status, comorbidity burden, renal function, and medication review

Safety

DOACs demonstrate similar or superior efficacy and safety compared with vitamin K antagonists in frail and multimorbid patients

Who this may help

Clinicians may use DOACs in real-world AF populations with frailty and multimorbidity, provided care is individualised with frailty screening and structured medication review. Integration of holistic management approaches, such as the ABC pathway, is recommended to optimise outcomes.

Plain-language summary

A narrative review synthesizing evidence on DOAC safety and efficacy in complex AF phenotypes, offering expert recommendations for individualized care rather than reporting a single original empirical result.

Study design

As stated by the source record.

MethodsTargeted searches of PubMed/MEDLINE, Embase, and major cardiology society documents (ESC/EHRA) performed from inception to May 2025, prioritising randomised trials and complemented by large observational studies and registries.

DesignNarrative review

PopulationAtrial fibrillation patients with frailty, multimorbidity, and/or polypharmacy—populations underrepresented in randomised clinical trials.

InterventionDirect oral anticoagulants (DOACs)

ComparatorVitamin K antagonists (warfarin) and other anticoagulation strategies

Clinical bottom line

Caveats

Narrative review without systematic methodology; no aggregate effect sizes, confidence intervals, or p-values reported for DOAC versus warfarin comparison
No quantification of drug-drug interaction frequency or clinical magnitude in DOAC-treated complex patients
Future research identified as needed on prospective studies and implementation strategies in underrepresented populations
Individual trial and observational study results not enumerated; strength of underlying evidence base not transparent

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

limited

Narrative review synthesizing trials, observational studies, and registries; not a systematic or meta-analytic approach.

Directness

strong

Directly addresses DOACs in frail, multimorbid, polypharmacy-exposed AF patients—the target population.

Consistency

moderate

Available evidence indicates similar or superior DOAC efficacy and safety; no internal conflicts reported but limited detail on variation.

Risk of bias

limited

Narrative review; no formal quality appraisal or bias assessment methodology stated.

Sample adequacy

insufficient

No aggregate sample sizes or meta-analytic pooling reported; scope depends on included primary sources.

What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.

Source abstract

INTRODUCTION: Direct oral anticoagulants (DOACs) are widely used for stroke prevention in atrial fibrillation (AF); however, patients encountered in real-world practice frequently exhibit frailty, multimorbidity, and polypharmacy, phenotypes underrepresented in randomized clinical trials. AREAS COVERED: This narrative review addresses the safety and efficacy of DOACs in clinically complex AF populations. Targeted searches of PubMed/MEDLINE, Embase, and major cardiology society documents (ESC/EHRA) were performed from inception to May 2025, prioritizing randomized trials and complemented by large observational studies and registries. Available evidence indicates that DOACs demonstrate similar or superior efficacy and safety compared with vitamin K antagonists in frail and multimorbid patients. Although polypharmacy increases the risk of drug-drug interactions, DOACs are associated with fewer interactions and simplified dosing strategies. Observational data support the real-world effectiveness of DOACs when treatment is individualized according to frailty status, comorbidity burden, renal function, and medication review. EXPERT OPINION: DOACs can be used safely and effectively in complex AF patients when care is individualized. Integration of frailty screening, structured polypharmacy review, and holistic management approaches, such as the ABC pathway, may improve outcomes. Future research should focus on prospective studies and implementation strategies in underrepresented high-risk populations.

Follow from this

Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.

Heart Failure Treatment and ManagementGregory Y.H. LipPanteleimon E. Papakonstantinou