Primary Non-Adherence and Associated Factors in Patients with Atrial Fibrillation in Germany: A Retrospective Cohort Study

Q: What are the key findings of this study?

Direct factor Xa inhibitors were associated with lower odds of 30-day primary non-adherence compared with vitamin K antagonists (10.1% vs 14.4%; OR 0.67, 95% CI 0.62–0.72) in AF patients.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Atrial fibrillation (n=53815). Intervention: Direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) and direct thrombin inhibitors (dabigatran) vs. Vitamin K antagonists (phenprocoumon, warfarin). Primary outcome: Primary non-adherence (failure to dispense a drug of the same anticoagulant class within 30 days of the first prescription) (OR 0.67, 95% CI 0.62–0.72, p=<0.01).

Q: What does this research mean for the field?

Direct factor Xa inhibitors are associated with significantly lower odds of 30-day primary non-adherence compared with vitamin K antagonists in patients with atrial fibrillation. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To estimate primary non-adherence—failure to dispense a newly prescribed medication within 30 days—to oral anticoagulants in patients with atrial fibrillation in Germany and identify associated factors.

Karel Kostev; Beate Leppert; Maximilian Peters; Henning Sievert; Marcel Konrad; Mark Luedde

doi:10.3390/jcdd13100499

October 3, 2026Journal of Cardiovascular Development and DiseaseOpen Access

Primary Non-Adherence and Associated Factors in Patients with Atrial Fibrillation in Germany: A Retrospective Cohort Study

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Key result

Direct factor Xa inhibitors linked to ~33% lower odds of primary non-adherence vs VKAs.

OR 0.67
95% CI 0.62–0.72
P<0.01
n=53,815

Why the study?

Primary non-adherence to newly prescribed oral anticoagulants in patients with atrial fibrillation in Germany and its associated factors were not well characterized.

Does prescribing direct oral anticoagulants (direct factor Xa inhibitors or direct thrombin inhibitors) reduce 30-day primary non-adherence compared with vitamin K antagonists in patients with atrial fibrillation?

Key Points

To estimate primary non-adherence—failure to dispense a newly prescribed medication within 30 days—to oral anticoagulants in patients with atrial fibrillation in Germany and identify associated factors.
Retrospective cohort study linking first prescriptions of vitamin K antagonists, direct thrombin inhibitors, or direct factor Xa inhibitors (2016–2025) from the IQVIA Disease Analyzer database with pharmacy dispensing records in the Longitudinal Prescription database.
Included 57,290 first prescriptions across 53,815 patients (mean age 75.5 years; 49.7% women), excluding prescriptions preceded by dispensing of the same class within 365 days.
Assessed primary non-adherence within 30 days and evaluated associated factors using multivariable logistic regression with generalized estimating equations.
Primary non-adherence occurred in 10.6% of first prescriptions (6,055/57,290), occurring in 14.4% for vitamin K antagonists, 11.7% for direct thrombin inhibitors, and 10.1% for direct factor Xa inhibitors.
Lower odds of primary non-adherence were associated with direct factor Xa inhibitors (OR 0.67; 95% CI 0.62–0.72), direct thrombin inhibitors (OR 0.82; 95% CI 0.70–0.95; p=0.011), prior myocardial infarction (OR 0.79; 95% CI 0.67–0.94), and dementia (OR 0.85; 95% CI 0.75–0.96), whereas ischemic heart disease (OR 1.18; 95% CI 1.10–1.27) and hypertension (OR 1.11; 95% CI 1.04–1.18) were associated with higher odds.
Non-dispensing of the first prescription strongly predicted non-dispensing of subsequent prescriptions (OR 12.47; 95% CI 11.84–13.13), occurring in 72.5% versus 15.3% of patients whose initial prescription had been dispensed.

Study Design

Type

Cohort (n=53,815)

Multicenter

Yes

Structured PICO

Does prescribing direct oral anticoagulants (direct factor Xa inhibitors or direct thrombin inhibitors) reduce 30-day primary non-adherence compared with vitamin K antagonists in patients with atrial fibrillation?

P

Population

53,815 adults (mean age 75.5 years, 49.7% women) with atrial fibrillation receiving 57,290 first prescriptions of an oral anticoagulant class in German outpatient practices, followed for 30 days (and up to 365 days) for pharmacy dispensing.

E

Exposure

First prescription of direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) or direct thrombin inhibitors (dabigatran)

C

Comparator

First prescription of vitamin K antagonists (phenprocoumon, warfarin)

O

Outcome

Primary non-adherence (PNA), defined as failure to dispense a drug of the same anticoagulant class within 30 days of the prescription datesurrogate

Main Result

Odds Ratio: 0.67 (95% CI 0.62–0.72)

Absolute Event Rate: 10.1% vs 14.4%

p-value: p=<0.01

Approximately one in ten first oral anticoagulant prescriptions for atrial fibrillation in German primary care is not dispensed within 30 days, with significantly higher primary non-adherence for vitamin K antagonists than for direct factor Xa inhibitors.

Limitations

Observational design reflects associations rather than causal relationships and residual confounding cannot be excluded.
CHA2DS2-VASc and HAS-BLED scores were approximated from diagnoses and prescriptions without laboratory values (e.g., labile INR or blood pressure measurements).
Socioeconomic status, out-of-pocket costs, distance between practice and pharmacy, and detailed cognitive function were unavailable.
Privately insured patients are not represented in the LRx database, and prescriptions initiated in hospitals or cardiology practices were not directly captured.
No information on the reasons for non-dispensing or switching, nor on whether dispensed medications were actually taken.
Observational design with potential residual confounding
CHA2DS2-VASc and modified HAS-BLED scores were approximated without laboratory values (no INR or blood pressure measurements)
Lack of data on socioeconomic status, out-of-pocket costs, smoking, and distance to pharmacy
Excludes privately insured patients and therapy directly initiated in hospitals or specialist cardiology practices
No information on reasons for non-dispensing or whether dispensed medication was actually ingested

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Answers are grounded in this paper and cite their sources.

Implication

Direct factor Xa inhibitors may reduce primary non-adherence versus vitamin K antagonists in AF; leaves open causal effects and generalizability pending trials.

Abstract

Background: Primary non-adherence (PNA)—failure to dispense a newly prescribed medication—is an early barrier to effective treatment. This study aimed to estimate PNA to oral anticoagulants in patients with atrial fibrillation (AF) in Germany and to identify associated factors. Methods: In this retrospective cohort study, first prescriptions of vitamin K antagonists (VKAs), direct thrombin inhibitors, or direct factor Xa inhibitors issued to AF patients between 2016 and 2025 in the IQVIA Disease Analyzer database were combined with pharmacy dispensing records in the Longitudinal Prescription (LRx) database. First prescriptions preceded by a dispensing of the same class within 365 days were excluded. PNA was defined as failure to dispense within 30 days; associated factors were assessed using logistic regression with generalized estimating equations. Results: The study included 57,290 first prescriptions in 53,815 patients (mean age 75.5 years; 49.7% women). PNA occurred in 10.6% (VKAs 14.4%, direct thrombin inhibitors 11.7%, direct factor Xa inhibitors 10.1%). Direct factor Xa inhibitors (odds ratio [OR] 0.67; 95% confidence interval [CI] 0.62–0.72), prior myocardial infarction (OR 0.79), and dementia (OR 0.85) were associated with lower odds of PNA, whereas ischemic heart disease (OR 1.18) and hypertension (OR 1.11) were associated with higher odds. Non-dispensing of the first prescription was strongly associated with non-dispensing of subsequent prescriptions. Conclusions: Approximately one in ten first oral anticoagulant prescriptions in AF was not dispensed within 30 days, most frequently for VKAs.

Discussion

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Cite This Study

Kostev et al. (2026) conducted a cohort in Atrial fibrillation (n=53,815). Direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) and direct thrombin inhibitors (dabigatran) vs. Vitamin K antagonists (phenprocoumon, warfarin) was evaluated on Primary non-adherence (failure to dispense a drug of the same anticoagulant class within 30 days of the first prescription) (OR 0.67, 95% CI 0.62–0.72, p=<0.01). Direct factor Xa inhibitors were associated with lower odds of 30-day primary non-adherence compared with vitamin K antagonists (10.1% vs 14.4%; OR 0.67, 95% CI 0.62–0.72) in AF patients.

synapsesocial.com/papers/6ac72a2936c8cd5d094bf1db https://doi.org/10.3390/jcdd13100499

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Primary Non-Adherence and Associated Factors in Patients with Atrial Fibrillation in Germany: A Retrospective Cohort Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Primary Non-Adherence and Associated Factors in Patients with Atrial Fibrillation in Germany: A Retrospective Cohort Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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