Atrial fibrillation (AF) is an important risk factor for ischemic stroke [
The aim of study was to assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors influencing the initiation of OAC in possible eligible patients, based on the nationwide Danish Stroke Registry, in the period from 2003 to 2011.
The Danish National Health Service provides tax-supported health care for all citizens, including access to hospital care with no costs. All medical emergencies, including stroke, are exclusively treated at public hospitals, and the visitation is based upon catchment’s area and diagnoses. The Danish Stroke Registry (DAP), former a part of the Danish National Indicator Project, is a nationwide stroke registry initiated in 2003. DAP monitors and improves the quality of care provided by hospitals by benchmarking. Evidence based standards, indicators, and prognostic factors are used. Data is collected prospectively in all 35 stroke units in the country by health care specialists, in the stroke units, through a mandatory, standardized registration form [
All data was provided by DAP. Data regarding the following items were recorded during hospital stay by treating doctors: discharge diagnosis, date of admission, atrial fibrillation (yes/no, regardless if previous, current, paroxysmal, or chronic), and oral anticoagulant therapy (prescribed, not prescribed without stated reason or contraindication present). Until approval of dabigatran etexilate for the Danish market in August 2011, OAC consisted of VKA only, and >95% of VKA was warfarin. Only use of OAC and not the specific product is recorded in the registry; however, the vast majority of patients were prescribed warfarin. OAC in patients with AF within 10 days of stroke onset is a quality indicator. If a patient has AF the treating physician records if OAC is given; is not initiated in spite of existing indication or is considered contraindicated. If considered contraindicated, the cause is indicated by selecting one of the following: Recent surgery, recent bleeding, thrombocyte inhibitor treatment mandatory, uncontrolled hypertension, hemorrhagic diastase, dementia, alcoholism, patient rejecting OAC therapy, pregnancy, moribund patient, high fall risk, previous bleeding, high age, non-compliance, significant liver failure, kidney failure, endocarditis in native valves, and large cerebral infarction with edema and/or high bleeding risk. Data regarding the following patient characteristics included: age, sex, alcohol consumption (≤14/21, >14/21 drinks (5 g alcohol) per week for women and men, resp.), smoking habits (current smoker, occasionally smoker, former smoker, or never-smoker), marital status (cohabiting, living alone, or other), type of residence (private home, nursing home, another form of residence), stroke severity at admission assessed by the Scandinavian Stroke Scale (SSS) score (0–58 points) [
Data was obtained from DAP covering the period from 2003 to 2011. 105,968 patients were included in the registry. Entries dated before 2003 and after 2011 (
All statistical analyses were done using IBM SPSS Statistics version 20.0.0.
Frequency analysis was used to investigate the use of OAC in patients with ischemic stroke and AF. Frequency analysis was used to describe distribution of OAC status, gender, and stroke severity according to age. Characteristics of patients in therapy and not in therapy were compared using
Multiple logistic regression analysis was performed to identify independent predictors of OAC prescription. The variables included were age (categorized into four groups), gender, stroke severity measured by SSS score (categorized into four groups), institutionalization, living alone, smoking, excessive alcohol consumption, and a history of diabetes, acute myocardial infarction, hypertension, or previous stroke.
Values not stated were fused with system missing values, included in analysis, and reported as missing. In patient characteristics, missing values were excluded, and the total valid count for each risk factor is reported.
The study was approved by the Danish Data Protection Agency, file number 2007-58-0015.
Amongst the 55,551 ischemic stroke patients, 9,482 (17.1%) had AF. Of these, 3,938 (41.5%) were prescribed OAC; 3,385 (35.7%) were registered as having a contraindication, whilst 1,459 (15.4%) were not prescribed OAC without a stated reason, and missing values constituted overall 700 (7.4%). The proportion of patients in OAC amongst patients without a contraindication was on average 73.0%, reaching 91.9% in 2011. During the study period the rates of OAC increased from 36.0 to 46.6%; the rates of contraindications increased from 18.9 to 42.5%, whereas the rates of patients not prescribed OAC, without a stated contraindication, decreased during period from 38.5% in 2003 to 3.7% in 2011. The amount of missing values remained the same. It was 6.6% in 2003 versus 7.4% in 2011.
Characteristics of the patients in OAC and not in OAC are presented in Table
Characteristics of ischemic stroke patients with AF (
Characteristics | OAC ( |
No OAC ( |
Total |
|
||
---|---|---|---|---|---|---|
Mean (SD) |
|
Mean (SD) |
|
|||
Age (years) | 76.5 (±9.5) | 81.7 (±9.5) | 8,782 | <0.0001 | ||
SSS score (points) | 43 (±15) | 32 (±18) | 8,272 | <0.0001 | ||
Gender | ||||||
Female | 1,812 (46.0) | 2,888 (59.6) | 8,782 | <0.0001 | ||
Male | 2,126 (54.0) | 1,956 (40.4) | ||||
Institutionalized | ||||||
Yes | 193 (5.1) | 792 (17.3) | 8,354 | <0.0001 | ||
No | 3,591 (94.9) | 3,778 (82.7) | ||||
Previous stroke | ||||||
Yes | 1,174 (30.7) | 1,572 (34.0) | 8,447 | 0.001 | ||
No | 2,656 (69.3) | 3,045 (66.0) | ||||
Living alone | ||||||
Yes | 1,629 (42.5) | 2,562 (55.2) | 8,476 | <0.0001 | ||
No | 2,205 (57.5) | 2,080 (44.8) | ||||
Smoking | ||||||
Yes | 799 (24.8) | 805 (23.6) | 6,635 | 0.232 | ||
No | 2,420 (75.2) | 2,611 (76.4) | ||||
Excessive alcohol consumption | ||||||
Yes | 161 (4.7) | 184 (5.0) | 7,077 | 0.581 | ||
No | 3,244 (95.3) | 3,488 (95.0) | ||||
Diabetes mellitus | ||||||
Yes | 620 (16.1) | 759 (16.2) | 8,521 | 0.856 | ||
No | 3,230 (83.9) | 3,912 (83.8) | ||||
Acute myocardial infarction | ||||||
Yes | 553 (14.7) | 687 (15.4) | 8,226 | 0.431 | ||
No | 3,200 (85.3) | 3,786 (84.6) | ||||
Hypertension | ||||||
Yes | 2,247 (59.8) | 2,679 (59.3) | 8,278 | 0.668 | ||
No | 1,513 (40.2) | 1,839 (40.7) |
The proportion of patients receiving OAC was decreasing with age, from 56.5% in the age range 51–60 years to 16.4% in the age range 91–100 years. The proportion of patients with contraindications showed the opposite trend and increased with age, from 24.1% in the age range 51–60 years to 58.7% in the age range 91–100 years. The proportion of not prescribed without stated reason and missing values were only slightly increasing with age from 14.3% and 5.1% in the age range 51–60 years to 18.2% and 7.3% in the age range 91–100 years, respectively (Figure
Age distribution of OAC status, gender, and stroke severity in AF patients in the age range of 51–100 years (
(
(
(
In the logistic regression model relatively younger age, less severe stroke, and male gender were significant positive predictors of OAC prescription, whereas institutionalization, smoking, and excessive alcohol consumption were significant negative predictors of OAC prescription (
Multiple logistic regression analysis of treatment with OAC in ischemic stroke patients with AF (
|
OR | 95% CI | |
---|---|---|---|
Age group (years) | |||
>84 | Reference category | ||
75–84 | <0.0001 | 1.984 | 1.716–2.293 |
65–74 | <0.0001 | 2.780 | 2.326–3.321 |
<65 | <0.0001 | 2.721 | 2.170–3.413 |
SSS group (points) | |||
Very severe (0–14) | Reference category | ||
Severe (15–29) | <0.0001 | 1.917 | 1.502–2.447 |
Moderate (30–44) | <0.0001 | 2.468 | 1.982–3.074 |
Mild (45–58) | <0.0001 | 3.881 | 3.170–4.751 |
Male gender | 0.004 | 1.197 | 1.058–1.354 |
Institutionalization | <0.0001 | 0.430 | 0.337–0.548 |
Smoking | 0.053 | 0.871 | 0.756–1.002 |
Excessive alcohol consumption | 0.007 | 0.692 | 0.528–0.906 |
In the present study positive predictors of OAC were relatively younger age, less severe stroke, and male gender, while negative predictors were excessive alcohol consumption, smoking, and institutionalization. Age was one key factor influencing OAC decision. On average 41.5% of all patients admitted from 2003 to 2011 with ischemic stroke and AF were prescribed OAC. A majority of patients not in OAC had a contraindication.
OAC was administered in 41.5% of ischemic stroke patients with AF, in conformity with results from a nationwide Swedish registry (Riks-Stroke), where 11% received primary prevention and 33.5% received secondary prevention [
As it is well known from previous studies, we found that stroke severity increased with age [
In our model the strongest predictor of OAC prescription was stroke severity, with higher SSS score associated with higher odds; the more severe the stroke was the less likely the patient was to be receiving OAC. This is in conformity with the finding in Riks-Stroke that being fully conscious on admission was associated with OAC prescription [
In our model comorbidity such as hypertension and diabetes did not predict OAC, in line with Stockholm Cohort-Study [
The strengths of the present study include a population-based design that comprises the entire Danish population and reflects routine clinical practice. Health care specialists collected detailed quality data prospectively, which minimizes the risk of selection and information bias. Minimal exclusions were made, since the exclusions of patients with missing data potentially would have introduced selection bias. Risk of referral bias was low, since it can be assumed that all patients with acute symptoms of stroke are referred to the public health care system if hospitalized. Traditionally hospitalization rates are high after stroke in Denmark [
The weaknesses of the present study include the retrospective design and the risk of misclassifications during data collection in routine clinical settings. Some change of practice may have occurred during the 9-year period. However, participation in DAP is mandatory for all departments treating patients with acute stroke, and extensive efforts are made to ensure data validity. Missing values in some items were decreasing during study period, reflecting better implementation of DAP. Although missing data should always be a reason for concern, we have no reason to believe these substantially influenced results, since the missing data were incidental; however, in some analyses this caused substantial exclusion of patients. Further, more detailed data on patients for example, CHA2DS2-VASc score, might have contributed to a more detailed interpretation of our findings; however, these data were not collected.
The present study stresses the importance of continued attention to therapy rates. However, it also raises the question if alleged underuse of OAC really is of the previously assumed size or could for a majority be explained by contraindications and risk/benefit ratios made by clinicians on an individual patient level. When the decision about OAC is made it is important to be knowledgeable about present guidelines and actual contraindications, especially when treating older patients, patients with severe strokes, or institutionalized patients, which may frequently lead to not treating the patient. Novel OAC (NOAC) drugs such as dabigatran, rivaroxoban, and apixaban show efficacy and safety at least comparable to warfarin [
In summary, relatively younger age and less severe stroke were strong positive predictors of OAC. Smoking and excessive alcohol consumption as well as being institutionalized were negative predictors of OAC. Male gender was a weak but significant positive predictor. Contraindications were generally present in patients not in therapy. Underuse of OAC may be overestimated and represents risk/benefit estimates in individual high-risk patients.
The authors are grateful to Centre for Clinical Quality and Health Informatics West and all stroke units in Denmark for providing data. The authors are also grateful to Susanne Zielke Schaarup, senior nurse, MHSc, Copenhagen University Hospital Bispebjerg, for continuously providing good advice about The Danish Stroke Registry. Louisa M. Christensen has received honoraria and conference attendance grants from Bayer Denmark, Boehringer-Ingelheim Denmark, and Medtronic Denmark. Hanne Christensen is Associate Research Professor funded by Capitol Region of Denmark.