To reduce strokes in patients with non-valvular atrial fibrillation (AF), guidelines recommend therapy with oral anticoagulants (OACs), depending on the patients’ CHA2DS2VASc score (1). The German Cardiac Society and the German Society of Internal Medicine have published recommendations from their initiative “Klug entscheiden” [“Choosing wisely“], which include positive and negative recommendations for patients with AF (2). We studied guideline adherence with respect to overtreatment or undertreatment with OACs in the Rhine-Neckar area.
Acknowledgments
Translated from the original German by Birte Twisselmann, PhD.
Footnotes
Funding
The ARENA project was funded by the German Cardiac Society’s center for cardiological health services research, by the German Cardiac Society, Düsseldorf; the German Heart Foundation, Frankfurt; the Institute for Myocardial Infarction Research, Ludwigshafen, and by Boehringer-Ingelheim, Germany.
Conflict of interest statement
DT received consultancy fees from Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer Pharma. He received lecture honoraria from Bayer Vital, Boehringer Ingelheim Pharma, Bristol-Myers Squibb, Daiichi Sankyo, Medtronic, Pfizer Pharma, Sanofi-Aventis, Abbott/St Jude Medical, and ZOLL CMS. He is a member of the steering committee of the AFNET reg. assoc. and the speaker of the Basic Science Cluster of the German Cardiac Society.
UZ received lecture honoraria from Bayer-Vital, Boehringer-Ingelheim, BMS, Daiichi Sankyo, and Pfizer.
The remaining authors declare that no conflict of interest exists.
Methods
The ARENA project is a campaign to improve treatment of AF in the metropolitan region Rhine-Neckar. One component is a registry in which patients with AF were prospectively registered and followed up (3). The present analysis includes all persons for whom we were able to calculate a CHA2DS2VASc score. Since in patients without an indication for treatment with OACs, anticoagulation is recommended for at least four weeks after cardioversion or pulmonary vein isolation, these were excluded from our analysis regarding overtreatment. To determine independent predictors for treatment with OACs, we calculated one logistic regression model each for patients with class I indication and without indication.
Results
Between 18 August 2016 and 13 July 2019, 2769 patients in 11 hospitals (n=1908, 68.9%) and five practices were included. The Figure shows the classification into persons with class I indication (CHA2DS2VASc score > 1 men and > 2 women), class IIa indication (CHA2DS2VASc score 1 men and 2 women) and without indication for oral anticoagulants (CHA2DS2VASc score 0 men and 1 women).
Figure.
Flow chart showing stratification of patients into three groups with class I, class IIa, and without indication for oral anticoagulation.
Class I indication (CHA2DS2VASc score > 1 men and > 2 women), class IIa indication (CHA2DS2VASc score 1 men and 2 women) and no indication for OAC (CHA2DS2VASc score 0 men and 1 women). Of 2769 persons included in ARENA, 421 were excluded from this analysis (CHA2DS2VASc score not documented n = 242, antithrombotic medication not documented n = 118, after interventional occlusion of atrial appendage n = 23, parenteral anticoagulation n = 38). OAC, oral anticoagulation; LAA, left atrial appendage; KV, cardioversion; PVI, pulmonary vein isolation
Of 2348 persons in the analysis, 1946 (83%) had a class I indication. In these, treatment with oral anticoagulants was done—with vitamin K antagonists (VKAs) in 23.7% and with non-VKA oral anticoagulants (NOACs) in 76.3%, with 134 (6.9%) not receiving any OACs. Of these 134 patients, 81 (60%) were treated with antiplatelets. Predictors for OAC treatment were known AF, persistent or permanent AF and valve diseases), whereas increased bleeding risk was associated less often with treatment with OACs (table).
Table. Criteria in favor of and against treatment with oral anticoagulation in patients with class I indication for anticoagulation.
| Odds ratio | [95% CI] | |
| Known AF | 2.50 | [1.54; 4.07] |
| Persistent or permanent AF | 1.75 | [1.13; 2.72] |
| Comorbid valve disease | 1.94 | [1.13; 3.33] |
| Heart failure | 1.71 | [0.99; 2.74] |
| Age (per 10 years) | 0.96 | [0.76; 1.21] |
| Female sex | 1.22 | [0.80; 1.85] |
| Vascular disease | 1.05 | [0.70; 1.57] |
| Hypertension | 1.07 | [0.63; 1.82] |
| Diabetes | 1.15 | [0.73; 1.81] |
| Prior thrombembolism | 1.07 | [0.61; 1.88] |
| Increased bleeding risk | 0.52 | [0.28; 0.95] |
CI, confidence interval; AF, atrial fibrillation
Of the 264 patients with a class IIa indication, 217 (82.2%) were treated with OACs (VKA 19.4%, NOACs 80.6%), 9 (3.4%) were treated with thrombocyte inhibitors, and 38 (14.4%) did not receive antithrombotic treatment. Only 80 patients had no indication for OACs treatment; of these, 31 (38.8%) were still treated with OACs, and 28 (92%) of these with NOACs. Predictors for overtreatment were persistent or permanent AF, valve diseases, and older age.
To summarize, 1861 (91.6%) or 2026 persons for whom an unequivocal recommendation existed received the treatment recommended by the guideline. Of the 2290 discharged patients, 2141 (93.5%) were followed up. The 1-year Kaplan Meier estimates for the combined endpoint death, stroke, myocardial infarction, and severe bleeding in the three groups indicated that for class I (9.7% versus 13.3%, hazard ratio 0.69, 95% confidence interval: [0.42; 1.14]) and class IIa indication (1.9% versus 4.3%, HR 0.42, [0.08; 2.31]), OAC treatment was associated with a trend towards fewer events. By contrast in those persons in whom no indication existed, numerically more events were seen when OACs were administered (3.2% versus 2.1%, HR 1.50, [0.09; 23.98]).
Discussion
This analysis of patients with AF in the Rhine-Neckar area showed a high degree of adherence to treatment with OACs. More than 90% of patients with an unequivocal recommendation were treated in a guideline-conform manner. Only 7% of persons with a class I indication were not treated with OACs—against the recommendation of the guidelines—and therefore formally undertreated. The crucial factor of influence against OACs is an increased risk of bleeding. Patients with a class IIa indication were treated with anticoagulants in more than 80% of cases, which means that in case of doubt, OAC tends to be given.
In contrast to the small proportion of patients who were undertreated, the proportion who were overtreated was high, at 39% of patients without an indication for OAC. This shows the tendency to administer OACs in patients with atrial fibrillation independently of their risk of systemic embolism and stroke. But this group is numerically small—31 persons. A review article including almost 10,000,000 patients from all five continents found an increase in patients treated with OACs from 42% in 2010 to 78% in 2018 (4). Comparable results from Germany exist, and this was also associated with the introduction of NOACs (5).
In our study only 7% of patients with a clear indication were not treated with anticoagulants, a rate that is very low in the international comparison. One explanation may be selection bias as persons who agree to participate in a registry represent a positive selection. As in previous studies (5), ARENA showed for guideline-conform treatment a numerically smaller rate of clinical events. For OAC therapy in patients without any indication the trend went in the opposite direction.
In sum, our data show good guideline adherence regarding OAC treatment in AF, and a lower event rate for guideline-adherent treatment.
References
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