Anticoagulants reduce the risk of thromboembolism and death in patients with atrial
fibrillation (AF).[1]
[2] Evidence-based clinical practice guidelines recommend anticoagulation based on the
CHA2DS2-VASc score to decrease the risk of stroke in patients with AF.[3] Conversely, randomized trials demonstrate the inadequacy of antiplatelet agents
compared with anticoagulants for stroke prevention in at-risk AF patients.[4]
[5] We have reported in our AF outpatient cohort study that anticoagulants were prescribed
in half of the patients with an indication for anticoagulation.[6] We now analyze this database to determine clinical factors associated with non-prescription
of anticoagulation in AF.
We reviewed 5,062 consecutive records of patients who had the diagnosis of AF entered
into the electronic health record within our outpatient clinic network between March
2013 and March 2014. We utilized the 2011 American College of Cardiology/American
Heart Association/Heart Rhythm Society guidelines, which recommended anticoagulation
in AF patients with a CHA2DS2-VASc score ≥2,[3] to narrow our final cohort to 3,677 patients. The aim of the study was to identify
factors independently associated with nonprescription of anticoagulation for stroke
prevention in AF patients with CHA2DS2-VASc score ≥2. Anticoagulation was defined as the prescription of any United States
Food and Drug Administration–approved anticoagulant therapy for stroke prevention
in patients with AF. Vascular disease included coronary artery disease (CAD) and peripheral
arterial disease (PAD). Bleeding risk was estimated with the modified HAS-BLED score,
excluding fluctuation of the International Normalized Ratio (INR) because the computer
program could not search for labile INR.[7] To investigate associations with the nonprescription of anticoagulation, we undertook
a multivariate analysis by constructing hierarchical modified Poisson's regression
models with robust error variance, adjusted for patient- and practice-level characteristics
with a p-value of <0.10 by univariate analysis.[8] Covariates entered into the model were age, sex, body mass index (BMI), race, ethnicity,
hypertension, diabetes mellitus, heart failure (HF), CAD, PAD, chronic kidney disease,
prior stroke, liver disease, prior major bleeding, alcoholism, and antiplatelet therapy.
A relative risk greater than 1 corresponds to an increased probability of anticoagulation
nonprescription. We identified factors related to prescription of antiplatelet therapy
by using the same method. These models included site as a random effect to account
for patient clustering within sites. Statistical tests were two sided and considered
significant if they yielded a p-value of <0.05.
In total, 1,945 (52.9%) patients were prescribed anticoagulation and 1,732 (47.1%)
were not. [Table 1] summarizes the baseline characteristics and antiplatelet regimen of the study population.
Patients who were prescribed anticoagulation were older, had higher BMI, and presented
with higher rates of hypertension, HF, and prior stroke compared with those who did
not receive anticoagulation by univariate analysis. These differences were reflected
by higher CHA2DS2-VASc scores in the anticoagulant patient group (median [IQR]: 3 [3–5] vs. 3 [2–4];
p < 0.001). Antiplatelet therapy was prescribed for 40.7% of patients not receiving
anticoagulation and for 25.9% of those receiving anticoagulation (p < 0.001). Concomitant antiplatelet and anticoagulant therapies were more frequently
prescribed in patients with vascular disease (48.5 vs. 20.9%; p < 0.001). The proportion of patients receiving anticoagulation (with and without
an antiplatelet agent) increased with CHA2DS2-VASc score (p < 0.001) and with HAS-BLED score (p < 0.001).
Table 1
Baseline characteristics and antiplatelet regimen of atrial fibrillation patients
at risk of stroke as categorized by the 2011 American College of Cardiology/American
Heart Association/Heart Rhythm Society (CHA2DS2-VASc score ≥2) guidelines, stratified by prescription and nonprescription of anticoagulants
|
Characteristics
|
CHA2DS2-VASc score ≥2
(N = 3,677)
|
p-Value
|
|
Anticoagulation
|
|
Yes (N = 1,945)
|
No (N = 1,732)
|
|
Mean age ± SD, y
|
75.5 ± 10.0
|
74.0 ± 10.7
|
0.11
|
|
Male (%)
|
1,039 (53.4)
|
885 (51.1)
|
0.16
|
|
Mean BMI ± SD, kg/m2
|
29.3 ± 6.5
|
28.2 ± 6.1
|
<0.001
|
|
Race (%)
|
|
White
|
1,586 (81.5)
|
1,442 (83.3)
|
0.17
|
|
Black
|
125 (6.4)
|
81 (4.7)
|
0.02
|
|
Other
|
117 (6.0)
|
91 (5.2)
|
0.35
|
|
Clinical history (%)
|
|
Hypertension
|
1,459 (75.0)
|
1,205 (69.6)
|
<0.001
|
|
Diabetes mellitus
|
459 (23.6)
|
367 (21.2)
|
0.08
|
|
Heart failure
|
463 (23.8)
|
309 (17.8)
|
<0.001
|
|
CAD
|
574 (29.5)
|
514 (29.7)
|
0.91
|
|
Valvular heart disease
|
361 (18.6)
|
293 (16.9)
|
0.19
|
|
PAD
|
127 (6.5)
|
98 (5.7)
|
0.30
|
|
CKD
|
189 (9.7)
|
194 (11.2)
|
0.14
|
|
Prior stroke
|
293 (15.1)
|
149 (8.6)
|
<0.001
|
|
Liver disease
|
30 (1.5)
|
31 (1.8)
|
0.60
|
|
Prior major bleeding
|
104 (5.3)
|
91 (5.2)
|
0.94
|
|
Alcoholism
|
31 (1.6)
|
37 (2.1)
|
0.26
|
|
Median CHA2DS2-VASc score
(Q1–Q3), points
|
3 (3–5)
|
3 (2–4)
|
<0.001
|
|
Median HAS-BLED score (Q1–Q3), points
|
2 (2–3)
|
2 (2–3)
|
0.21
|
|
Any antiplatelet (%)
|
503 (25.9)
|
705 (40.7)
|
<0.001
|
|
Dual-antiplatelet therapy (%)
|
40 (2.3)
|
<0.001
|
<0.001
|
Abbreviations: BMI, body mass index; CAD, coronary artery disease; CKD, chronic kidney
disease; PAD, peripheral artery disease; SD, standard deviation.
The rate of prescription of antiplatelet therapy alone did not vary significantly
according to the CHA2DS2-VASc score, between 17.2% for the CHA2DS2-VASc score of 2 and 22.1% for the CHA2DS2-VASc score of 5 (p = 0.72). In contrast, the rate of antiplatelet prescription increased with the HAS-BLED
score from 13.9% for HAS-BLED score of 1 to 54.1% for HAS-BLED score of 5 to 7 (p < 0.001).
After multivariate adjustment, the only factor independently associated with non-prescription
of anticoagulation was antiplatelet therapy (relative risk [RR] = 1.42; 95% confidence
interval [CI] = 1.32–1.53). Increased age (RR = 0.95; 95% CI = 0.92–0.98), increased
BMI (RR = 0.94; 95% CI = 0.92–0.98), hypertension (RR = 0.92; 95% CI = 0.85–0.99),
HF (RR = 0.87; 95% CI = 0.81–0.93), and previous stroke (RR = 0.77; 95% CI = 0.71–0.83)
were factors associated with increased frequency of anticoagulation prescription ([Fig. 1]). Male sex (RR = 1.05; 95% CI = 1.009–1.11), hypertension (RR = 1.08; 95% CI = 1.03–1.14),
and CAD (RR = 1.52; 95% CI = 1.42–1.64) were associated with prescription of antiplatelet
therapy.
Fig. 1 Multivariate analysis of factors associated with anticoagulant nonprescription versus
prescription in patients with atrial fibrillation at risk of stroke (CHA2DS2-VASc score ≥2). AC, anticoagulant; AF, atrial fibrillation; CI, confidence interval;
RR, relative risk.
Overall, we observed an inverse relationship between antiplatelet prescription and
anticoagulant nonprescription. Other investigators have reported alcohol abuse, cancer,
and falls as factors related to nonprescription of anticoagulation in addition to
antiplatelet prescription.[9]
In our analysis, the rate of antiplatelet prescription alone was constant, regardless
of stroke risk as defined by the CHA2DS2-VASc score. This suggests that antiplatelet therapy might have been prescribed for
an indication other than stroke prevention, such as prevention of cardiovascular events,
especially in patients with known vascular disease. Indeed, we identified risk factors
for atherosclerosis (i.e., male gender and hypertension), along with CAD itself, as
factors associated with prescription of antiplatelet therapy. An analysis of the PINNACLE
registry found, besides hypertension and CAD, that dyslipidemia and PAD were factors
associated with prescription of aspirin rather than anticoagulation.[10] Furthermore, the high rate of concomitant prescription of anticoagulant and antiplatelet
agents in patients with vascular disease may reflect providers' concerns regarding
the high risk of future vascular complications. We observed an increase in antiplatelet
prescription alone in patients with a high HAS-BLED score, potentially because of
concerns about causing bleeding with anticoagulant therapy. Other possible reasons
for antiplatelet therapy prescription may include primary prevention in patients at
high risk of cardiovascular disease, prevention of colon cancer,[11] or patient's refusal of anticoagulation.
Our analysis has limitations. The precise reason that prompted the providers to prescribe
antiplatelet therapy instead of guidelines-recommended anticoagulation was not recorded.
The frailty status and life expectancy of the patients were not recorded. We do not
have data regarding potential difficulties with warfarin management, which may have
led to its discontinuation. Finally, we were unable to determine whether antiplatelet
therapy was prescribed specifically for stroke prevention in AF or for some other
reason.
In conclusion, prescription of antiplatelet therapy was the only factor we identified
that was associated with omission of anticoagulants in this study of AF outpatients
at risk of stroke. Prevention of vascular events or concern for bleeding complications
could be motivating factors for antiplatelet prescription rather than anticoagulation
prescription. Factors compelling clinicians to prescribe antiplatelet therapy warrant
consideration when assessing rates of anticoagulation in patients with AF.
