Risk factors and stroke-preventing medications
among patients admitted for stroke – a sub-
study within the MedBridge trial
Lisa Bergström
Magister Degree Project in Drug Management, 15 hp,
Master of Science Programme in Drug Management,
Spring semester 2019, Uppsala University Hospital
Supervisor: Ulrika Gillespie
Examiner: Margareta Hammarlund-Udenaes
Division for Pharmacokinetics and Drug Therapy Department of Pharmaceutical Biosciences Faculty of Pharmacy
Uppsala University
a high-quality risk factor management is essential. However, some studies indicate that there is undertreatment of preventive medication for stroke or overtreatment of
medication that is not recommended for primary prevention for stroke. Aim: To investigate the baseline characteristics for patients admitted for ischemic stroke with a focus on the risk factors AF and DM and the medication for primary prevention at the time of admission. Methods and materials: Medication data from approximately 700 patients were collected from the electronic medical record system COSMIC and stored in the electronic data capture system Castor EDC together with data from all other participants, a total of 2646. Baseline characteristics such as “medical history”, “age”,
“eGFR” and “medication lists” were collected to assess and describe the risk factor pattern and the rate of prescribed preventive medicines. Results were presented using descriptive statistics.Results: Of all MedBridge patients with AF, the prescription rate of anticoagulants was 75,1 %, and of all MedBridge patients with DM, the rate of prescribed statins was 54,5 %. Among the 68 AF patients admitted for stroke, the prescription rate of anticoagulants was 64,7 %. Among the 85 DM patients admitted for stroke, the rate of prescribed statins was 55,3 %. After risk assessment, anticoagulant treatment was indicated in nine AF patients admitted for stroke that lacked treatment.
Anticoagulant treatment was indicated in four AF patients admitted for stroke that only had antiplatelets. Statin treatment was indicated in 13 DM patients admitted for stroke that lacked treatment. Conclusion: AF and DM are both common risk factors for ischemic stroke. Of all MedBridge patients with AF, approximately one in five lacked anticoagulant treatment, but there were only a few AF patients, out of those admitted for stroke, that lacked anticoagulants after risk assessment. However, this study indicates undertreatment with statins among patients with DM. Further studies should include more risk factors to get an insight into which part of the risk factor management and primary prevention of stroke that should be improved.
Populärvetenskaplig sammanfattning
Stroke är den andra vanligaste dödsorsaken i världen och är associerad med många riskfaktorer, så som förmaksflimmer, diabetes, höga blodfetter och högt blodtryck.
Risken att drabbas av en stroke kan reduceras genom att påverka dessa riskfaktorer och därför är det viktigt med en högkvalitativ riskfaktorhantering. Tidigare studier har visat att det både förekommer underförskrivning av skyddande läkemedel mot stroke samt överförskrivning av läkemedel som inte är rekommenderat som skydd mot stroke.
Syftet med detta arbete var att undersöka patienter som har kommit in till sjukhuset på grund av en stroke med fokus på riskfaktorerna förmaksflimmer och diabetes samt om patienterna hade skyddande läkemedel mot stroke vid tidpunkten för inläggning.
Läkemedelslistor från patienter samlades in från ett journalsystem och överfördes sedan till ett datainsamlingsprogram. Därefter överfördes den insamlade datan till Microsoft Excel för analysering. Av alla inkluderade patienter med förmaksflimmer, var andelen som hade fått antikoagulantia förskrivet 75,1 % och av alla inkluderade patienter med diabetes var andelen som hade fått statiner förskrivet 54,5 %. Av de 68 patienter med förmaksflimmer som lagts in på grund av en stroke, hade 64,7 % antikoagulantia förskrivet. Av de 85 patienter med diabetes som lagts in på grund av en stroke, hade 55,3 % en statin förskrivet. När riskbedömning hade genomförts bedömdes nio patienter med förmaksflimmer, som lagts in på grund av en stroke och saknade antikoagulantia, ha indikationen för det. Antikoagulantia var indicerat hos fyra patienter med
förmaksflimmer som hade lagts in på grund av en stroke och enbart hade
trombocythämmare. Statinbehandling bedömdes vara indicerat hos 13 patienter med diabetes som lagts in på grund av en stroke och saknade läkemedel mot höga blodfetter.
Sammanfattningsvis visar denna studie att det var ungefär en femtedel av alla inkluderade patienter med förmaksflimmer som saknade antikoagulantia. Av de patienter med förmaksflimmer som lagts in på grund av en stroke var det endast några få som saknade antikoagulantia efter riskbedömningen. Resultatet från studien tyder dock på en underförskrivning av statiner hos patienter med diabetes. Vidare studier bör inkludera fler riskfaktorer för att få en större bild av vilka delar i riskfaktorhanteringen som kan förbättras.
Table of Contents
Abstract____________________________________________________________________________________ 2 Populärvetenskaplig sammanfattning ___________________________________________________________ 3
1. Introduction __________________________________________________________________________ 6 1.1. Epidemiology of stroke ____________________________________________________________ 6 1.2. Stroke risk factors and prevention ____________________________________________________ 7 1.3. Medication related problems in patients with high risk for stroke ___________________________ 9 1.4. The Medication Review Bridging Healthcare study ______________________________________ 9
2. Aim ________________________________________________________________________________ 10 2.1. Objectives _____________________________________________________________________ 10
3. Methods and materials ________________________________________________________________ 11 3.1. Setting and study population _______________________________________________________ 11 3.2. Inclusion criteria (for the MedBridge study) ___________________________________________ 11 3.3. Exclusion criteria (for the MedBridge study) __________________________________________ 11 3.4. Data collection _________________________________________________________________ 12 3.5. Outcome measure and statistics ____________________________________________________ 12 3.6. Ethical approval ________________________________________________________________ 13
4. Results______________________________________________________________________________ 13 4.1. The rate of anticoagulant prescribing among all MedBridge patients with AF _________________ 13 4.2. The rate of prescribed lipid-lowering medication among all MedBridge patients with DM _______ 15 4.3. Risk factors and use of stroke-preventing medications among patients admitted for ischemic stroke 15 4.4. Lack of stroke preventive medication among patients admitted for stroke ____________________ 18
5. Discussion ___________________________________________________________________________ 18 5.1. Summary of the results ___________________________________________________________ 18 5.1.1. Anticoagulant treatment in patients with AF ____________________________________ 19 5.1.2. Lipid-lowering treatment in patients with DM ___________________________________ 20 5.2. Strengths and limitations __________________________________________________________ 21 5.3. Risk assessment methods _________________________________________________________ 22 5.4. Future directions ________________________________________________________________ 23 6. Conclusions _________________________________________________________________________ 23 References _________________________________________________________________________________ 24 Appendices ________________________________________________________________________________ 30
Appendix A: Risk assessment of AF patients admitted for ischemic stroke _________________________ 30 Appendix B: Risk assessment of DM patients admitted for ischemic stroke _________________________ 32
1. Introduction
1.1. Epidemiology of stroke
The elderly population is increasing worldwide, and an aging population is associated with more diseases (1,2). Like in many other countries, the aging population could lead to a heavy burden for the society in Sweden (3),and according to Persson et al., the economic burden of diseases such as stroke is important (3).
Stroke includes vascular diseases in the brain that leads to acute neurological symptoms (4). When a stroke occurs, it leads to oxygen deficiency in parts of the brain, causing damage to the brain tissue (4). Of all stroke cases, thrombosis cause 85 % (ischemic stroke) and the remaining 15 % is caused by hemorrhage (intracerebral hemorrhage and subarachnoid hemorrhage) (4). The effects of a stroke depend on which brain half is injured and how severely it is affected (5). In the worst case, the outcome is death (5).
According to the World Health Organization (WHO), stroke is the second most common cause of death worldwide representing 10,2 % of all deaths (6). Furthermore, stroke is the second leading cause of disability; in 2016, WHO estimated that stroke accounted for 5,2 % of disability adjusted life years (DALYs) from all causes (6). In Sweden, approximately 25 000-30 000 people suffer from a stroke every year, and it’s the third most common cause of death (4).
The statistics from WHO confirms that disabilities are common after a stroke;
disabilities include physical and cognitive impairments that often lead to long-term care and rehabilitation (3,7). Hospital care, including stroke units and rehabilitation, also results in costs for the society (3). A Swedish study showed that during the first year after an ischemic stroke the total per-patient cost was approximately 370 000 SEK (8) and according to Riksstroke, the average societal cost for a stroke patient is nearly 800 000 SEK for the remaining years of life for the patient (9). Furthermore, strokes can lead to a heavy burden, not only for the patient, but often the caregiver is affected as well (10).
1.2. Stroke risk factors and prevention
Ischemic stroke is associated with several risk factors, including atrial fibrillation (AF), diabetes mellitus (DM), hyperlipidemia and hypertension (11). The risk of suffering from a stroke could be reduced by modifying these risk factors, and therefore, a high- quality risk factor management is essential (12).
AF is one of the major causes of stroke, and studies confirm that AF strongly correlates with increased incidences of stroke (13,14). A Swedish study showed that among patients with an ischemic stroke, 31,9 % had the diagnose AF before the initial event (15). The same study pointed out that AF was the second most important risk factor for stroke (adjusted OR 1,82 95%Cl 1,73-1,91), after age ≥85 year (adjusted OR 1,84 95%Cl 1,72-1,96) (15). Among patients with AF, one of the strongest risk factors for ischemic stroke is age (11).
DM is also a risk factor for stroke; DM can contribute to pathologic changes in blood vessels, which can lead to stroke if it’s affecting cerebral vessels (16). Uncontrolled glucose levels lead to a higher risk of mortality and poorer post-stroke outcomes (16).
Also, metabolic syndrome is a risk factor for stroke (12). Metabolic syndrome refers to cardiometabolic risk factors such as obesity, raised serum triglycerides, reduced high- density lipoprotein cholesterol, glucose intolerance and high blood pressure (17).
To reduce the risk of stroke in patients with AF, medication treatment with
anticoagulants should always be considered (11). Studies show that anticoagulants, including vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs), significantly reduce the risk of stroke and mortality in patients with AF (18,19).To estimate the stroke risk CHA2DS2-VASc can be used, a high evidence-based score (Table 1) based on risk factors for stroke (11). Anticoagulants are recommended in men with risk score ≥ 2 and in women with ≥ 3 (11). However, renal function and the
expected bleeding risk must be considered before initiating anticoagulant treatment (11). The expected bleeding risk can be estimated with HAS-BLED (Table 2); patients who score 0-2 have a lower bleeding risk and patients who score 3-8 have a higher bleeding risk (11).
Studies show that statins reduce the risk from acute cardiovascular events, including stroke, with 25 % respective 48 % among patients with DM (20,21). The results correlate well with both National guidelines and European guidelines, saying that DM patients with high risk for cardiovascular disease (CVD) should be treated with statins in primary prevention for stroke (17,22). A way to estimate the CVD risk in patients with DM is by the National Diabetes Registers (NDRs) frame risk (23). Moreover, European guidelines point out that statin therapy is indicated in patients with DM and ischemic heart disease (IHD) or documented CVD, to reduce the risk for cardiovascular events, including stroke (24). Also, lipid-lowering, combined with well-controlled blood pressure and glucose levels is essential to reduce the stroke risk (24).
Table 1. CHA2DS2-VASc; risk factors and risk score (11)
Risk factors Risk score
Congestive Heart failure 1
Hypertension 1
Age ≥ 75 years 2
Diabetes 1
Stroke 2
Vascular disease 1
Age 65-74 years 1
Sex (female) 1
Table 2. HAS-BLED; risk factors and risk score (11)
Risk factors Risk score
Hypertension 1
Abnormal renal function 1
Abnormal liver function 1
Stroke 1
Bleeding history 1
Labile INR 1
Elderly (>65 years) 1
Alcohol concomitantly 1
1.3. Medication related problems in patients with high risk for stroke
Adverse drug events (ADEs) frequently occur in the elderly population and contribute to medication-related hospital admissions (MRAs) (25). ADEs are events that could be defined as “an injury resulting from medical intervention related to a medication” (26).
ADEs include events that occur from adverse drug reactions (ADRs), poor medication adherence but also from inappropriate prescribing such as over-, under- or
misprescribing (27,28).
Even though the use of anticoagulants is increasing among patients with AF in Sweden (29), some studies suggest that there is still undertreatment of anticoagulants in patients with AF (30), particularly in elderly patients (31). However, there is a limitation in one of the studies; because of the lack of information of patients with contraindications against anticoagulants, the undertreatment may be over-estimated (30).Furthermore, a study from Sweden showed an overuse of acetylsalicylic acid (ASA) in high-risk patients with AF (32),which correspond with neither National nor European guidelines saying that ASA is not recommended to prevent stroke in patients with AF (11,33).
Patients with DM and high risk for CVD should be treated with statins in primary prevention to reduce the risk of stroke (22), but studies indicate that there is an underuse of statins among patients with DM (34,35).
1.4. The Medication Review Bridging Healthcare study
The Medication Review Bridging Healthcare (MedBridge) study is an on-going cluster- randomized controlled trial (C-RCT) including four hospitals; Uppsala University Hospital and the hospitals of Enköping, Gävle and Västerås (36). The study is designed to determine the effects of pharmacist-led medication reviews together with active
follow-up among patients 65 years or older, this compared to solely pharmacist-led medical reviews and usual care (36). Patients that participate in this study are randomized into three different groups; intervention 1 (I1), intervention 2 (I2) and control. The I1-group include pharmacist-led medication reviews, I2 include the same as I1, but after discharge, this also includes an active follow-up. The control group receives usual hospital care without pharmacist involvement (36).
A previous pharmacy student did a sub-study within the MedBridge trial and found that cerebrovascular disease was one of the most prevalent diagnoses among the included patients (37). Therefore, it will be interesting to investigate these patients further, focusing on risk factors for stroke and the use of – or lack of – stroke preventive
medication at the time for admission. Some studies indicate that there is undertreatment of preventive medication for stroke (30,31,34,35) and overtreatment of medication that is not recommended for primary prevention for stroke (32). Therefore, it’s interesting to investigate this and to compare and discuss the results from MedBridge to previous studies, national register and guidelines.
2. Aim
To illustrate the risk factor pattern and the rate of prescribed preventive medicines in the MedBridge population, the aim of this study was to investigate the baseline
characteristics for patients admitted for ischemic stroke with a focus on the risk factors AF and DM and medication for primary prevention at the time of admission.
2.1. Objectives
Research questions:
• To investigate the rate of anticoagulant prescribing among all MedBridge patients with the diagnosis of AF.
• To investigate the rate of prescribed lipid-lowering medication among all MedBridge patients with the diagnosis of DM.
• To determine the number of patients with risk factors for stroke among patients admitted with an ischemic stroke and investigate these patients’ medication lists.
• To assess whether it exists under- over or misprescriptions of preventive medications among patients admitted for ischemic stroke.
• To investigate the reason why patients with high risk for stroke lack primary preventive medication.
3. Methods and materials
3.1. Setting and study population
This study was performed on patients in the MedBridge study. From a total of 2646 MedBridge patients, 2639 were included in this sub-study. Seven patients were excluded because it was not possible to determine which medication they had at the time of admission. The included number of patients with AF was 724 and 745 patients with DM. The included number of patients admitted for ischemic stroke was 324 and among these, 68 patients with AF and 85 patients with DM were included. The remaining 171 patients were included to assess and describe the risk factor pattern among the 324 patients admitted for ischemic stroke.
3.2. Inclusion criteria (for the MedBridge study)
Patients admitted to one of the study wards of the MedBridge study aged 65 years or older.
3.3. Exclusion criteria (for the MedBridge study)
Patients residing in another hospital’s county, patients having received medication review within the last 30 days, patients being in a palliative stage according to the medical record, and/or admitted for only one day was excluded.
3.4. Data collection
The first step in this study was to collect medication lists at the time of admission for approximately 700 patients from Uppsala University hospital and the hospital of Enköping from the electronic medical record system COSMIC. The medication lists from these patients were transferred and stored in the electronic data capture system Castor EDC, where it was pooled together with data from all the other patients in the MedBridge study, a total of 2646 patients. The data from the other patients had already been collected and stored by the investigators. After that, the data was transferred to Microsoft Excel.
The second step was “data-cleaning”. The extracted data were double checked to see if there were any missing or incorrect data. All patients in the MedBridge study were checked. Missing or incorrect data was corrected in Castor EDC with the right
information from COSMIC. Seven patients were excluded because it was not possible to determine which medication they had at the time of admission; 2639 patients were included. After the “data-cleaning”, the data was extracted to Microsoft Excel for further analyze.
The third step in the study was to collect relevant data for the results, which was done in the extracted Microsoft Excel file. The file included the baseline characteristics
“medical history”, ”age”, ”eGFR”, “sex” and “medication lists” of the patients.
3.5. Outcome measure and statistics
The first outcome measure of this study was the prescription rate of anticoagulants among patients with AF and the rate of prescribed lipid-lowering medication among patients with DM. The second outcome measure was the number of patients admitted for ischemic stroke, lacking stroke-preventing medication, that had the indication for it.
Descriptive statistics were used to present the baseline characteristics of the included patients in the MedBridge study. Bar charts were used to present the percentage of
MedBridge patients and of patients admitted for stroke. Microsoft Excel was used to calculate the statistics. The risk assessment tools “CHA2DS2-VASc” and “HAS-BLED”
were used to assess if anticoagulants were indicated among patients with AF admitted for stroke, not already using anticoagulants. In patients with DM admitted for stroke, the stroke risk was assessed according to European guidelines. COSMIC was used to find potential contraindications.
3.6. Ethical approval
Since this study is a part of the MedBridge study, no additional ethical approval was needed. The MedBridge study has received ethical approval from the Central Ethical Review Board in Sweden.
4. Results
4.1. The rate of anticoagulant prescribing among all MedBridge patients
with AF
From a total of 2639 patients included in this study, 724 had the diagnosis of AF. At the time of admission, 544 patients (75,1 %) were using anticoagulants (VKAs, NOACs, heparin). The number of patients with antiplatelet medication was 63 (8,7 %), 28 of these patients had an IHD. Patients who used a combination of anticoagulants and antiplatelets were 27 (3,7 %). Patients with neither anticoagulant nor antiplatelet
treatment were 90 (12.4 %). Results are presented in Figure 1. Of all anticoagulants, the most prescribed was apixaban, 43,6 % (Table 3).
Figure 1. The rate of anticoagulant prescribing among all MedBridge patients with AF.
*Patients with both anticoagulant and antiplatelet medication.
Table 3. The rate of prescribed substances among all anticoagulants. *Includes patients with only anticoagulants in their medication list and patients with both anticoagulants and antiplatelets.
Substance ATC-code Patients
(n)
Part of anticoagulants (%)
Apixaban B01AF02 249 43,6
Rivaroxaban B01AF01 59 10,3
Edoxaban B01AF03 2 0,4
Dabigatran B01AE07 16 2,8
Warfarin B01AA03 219 38,4
Dalteparin B01AB04 22 3,9
Enoxaparin B01AB05 4 0,7
Total - 571* 100,0
4.2. The rate of prescribed lipid-lowering medication among all
MedBridge patients with DM
Among all MedBridge patients, 745 had the diagnosis of DM. Of these 745, statins were used by 406 patients (54,5 %), at the time of admission. The number of patients with other lipid-lowering medication (fibrates, resins, ezetimibe) was 14 (1,9 %). Patients who used both a statin and other lipid-lowering medication were 15 (2,0 %). The number of patients without lipid-lowering medication was 310 (41,6 %). Results are shown in Figure 2.
Figure 2. The rate of prescribed lipid-lowering medication among all MedBridge patients with DM.
*Patients with both a statin and other lipid-lowering medication.
4.3. Risk factors and use of stroke-preventing medications among
patients admitted for ischemic stroke
The included number of patients admitted for ischemic stroke was 324. The number of patients with risk factors for stroke is shown in Table 4; the most common risk factor among the patients was hypertension, 66 %, and the least common risk factor was ischemic heart disease (IHD), 20,7 %. Patients with AF were 68 (21 %), and patients with DM were 85 (26,2 %).
Table 4. The risk factor pattern among patients admitted for ischemic stroke. *Observe that one patient may have more than one risk factor in their medical history.
Medical history
Patients (n)
Percent (%)
Atrial fibrillation (AF) 68 21,0
Diabetes Mellitus (DM) 85 26,2
Hypertension 214 66,0
Previous stroke 79 24,4
Ischemic heart disease (IHD) 67 20,7
Among patients with AF (n=68) admitted for ischemic stroke, 44 patients (64,7 %) had anticoagulants in their medication list. Patients with antiplatelets were 8 (11,8 %), 3 of these patients had an IHD. Patients who used a combination of anticoagulants and antiplatelets were 2 (2,9 %). The number of patients with neither an anticoagulant nor an antiplatelet were 14 (20,6 %). Results are shown in Figure 3. Of all anticoagulants, the most prescribed was warfarin, 39,1 % (Table 5). The most prescribed NOAC was apixaban, 23,9 % (Table 5).
Figure 3. The rate of anticoagulant prescribing among patients with AF admitted for ischemic stroke.
*Patients with both anticoagulant and antiplatelet medication.
Table 5. The rate of prescribed substances among all anticoagulants. *Includes patients with only anticoagulants in their medication list and patients with both anticoagulants and antiplatelets.
Substance ATC-code Patients
(n)
Part of anticoagulants (%)
Apixaban B01AF02 11 23,9
Rivaroxaban B01AF01 9 19,6
Edoxaban B01AF03 0 0,0
Dabigatran B01AE07 4 8,7
Warfarin B01AA03 18 39,1
Dalteparin B01AB04 2 4,3
Enoxaparin B01AB05 2 4,3
Total - 46* 100,0
Among patients with DM (n=85) admitted for ischemic stroke, 47 patients (55,3 %) had a statin in their medication list. Patients who used both a statin and other lipid-lowering medication (fibrates, resins, ezetimibe) were 2 (2,4 %). The number of patients without lipid-lowering medication were 36 (42,4 %). Results are presented in Figure 4.
Figure 4. The rate of prescribed lipid-lowering medication among patients with DM admitted for ischemic stroke. *Patients with both a statin and other lipid-lowering medication.
4.4. Lack of stroke preventive medication among patients admitted for
stroke
From a total of 68 AF patients admitted for stroke, 14 patients neither had anticoagulant nor antiplatelet in their medication list. Based on the risk assessment tools “CHA2DS2- VASc” and “HAS-BLED”, anticoagulant treatment was indicated in 9 of these 14 patients. The remaining 5 patients had either high HAS-BLED score and thus high bleeding risk or information from physicians in the medical record saying
anticoagulants had been ended due to prior bleeding. The data is presented in Table A1 in Appendix A. The number of patients that only had antiplatelet medication in their medication list was 8. In 4 of these patients, anticoagulant treatment was indicated. The remaining 4 patients had either high HAS-BLED score and thus high bleeding risk or information from physicians in the medical record saying anticoagulants had been ended due to prior bleeding. The data is presented in Table A2 in Appendix A.
From a total of 85 DM patients admitted for stroke, 36 patients lacked lipid-lowering medication. Based on European guidelines, statin treatment should be considered in 13 of these patients. Remaining 23 patients didn’t have any medical history of ICH or CVD. Therefore, the risk of suffering from a stroke couldn’t be estimated. The data is presented in Table B1 in Appendix B.
5. Discussion
5.1. Summary of the results
The four most common risk factors among patients admitted for stroke was
hypertension (66 %), DM (26 %), previous stroke (24,4 %), and AF (21 %). When comparing these numbers with the Riksstroke register, it’s well in line with how it looks at the national level. Riksstroke showed that the proportion with a medical history of hypertension was 64 %, DM; 22 %, previous stroke; 22 % and AF; 29 % among patients admitted for stroke and transient ischemic attack (TIA) (29).
5.1.1. Anticoagulant treatment in patients with AF
The results from this study show that there is a relatively high number of all patients with AF in the MedBridge study, that have anticoagulants prescribed (Figure 1). The rate of anticoagulant prescribing alone, and the prescription rate of both anticoagulant and antiplatelet among patients with AF admitted for ischemic stroke was slightly lower (Figure 3). When comparing the results from this current report with others, previous studies show a lower use of anticoagulants among patients with AF. One study from USA showed that only 34 % of patients with AF were prescribed warfarin (38). A systemic review from 2010 reported that over two-thirds of the included studies showed treatment levels under 60 % with anticoagulants among patients with AF (30).
According to a report from 2011, only 42 % of all individuals with AF were using anticoagulants in Sweden (39). One possible explanation of the low results from the previous studies could be that some studies are relatively old. According to Riksstroke, the prescribing of anticoagulants has continued to grow strongly among patients with AF in recent years (29). One study lacked information about patients with
contraindications against anticoagulants, and therefore, the undertreatment may be over- estimated (30). Another possible reason for the low results in the previous studies is that they only investigated the use of VKAs. A recent study indicated that the total
prescription of anticoagulants among patients with AF has increased since NOACs were introduced on the market (40). In this current study, apixaban was the most prescribed anticoagulant among all patients with AF. However, among AF patients admitted for stroke, warfarin was the most prescribed anticoagulant.
After risk assessment in AF patients admitted for ischemic stroke, there were only nine patients that lacked anticoagulants in whom such treatment was indicated (Appendix A, Table A1). Of those patients that only used antiplatelet medication, there were four patients in whom anticoagulants were indicated (Appendix A, Table A2). One possible reason that these patients lacked anticoagulants could be that the majority is “elderly elderly” (>80 years), which is associated with an increased risk of ADRs (41). However, age isn’t a contraindication for treatment with anticoagulants. There is strong scientific
evidence saying that the benefit of VKAs outweighs the risk in patients up to 90 years of age (42).
A problem worth discussing is that some patients were only treated with antiplatelets;
63 among all AF patients respective 8 among AF patients admitted for stroke. Both European and National guidelines point out that antiplatelet medication is not recommended to prevent stroke in patients with AF (11,33).A systematic review reported that both VKAs and NOACs are more effective in stroke prevention than antiplatelets (42). The same review also reported that there is no difference in the risk of severe bleedings between apixaban and ASA (42). However, antiplatelets are indicated in patients with IHD (11). Among all AF patients with antiplatelets, there were 28 with IHD and 3 among AF patients admitted for stroke. This is probably the reason why they have antiplatelets in their medication list. But still, dual therapy with anticoagulation and antiplatelet should be considered for up to 12 months to reduce the risk of CVD in patients with AF, and then anticoagulation in monotherapy (11).
5.1.2. Lipid-lowering treatment in patients with DM
Among all MedBridge patients with diabetes (n=745), the number of patients without lipid-lowering medication was 310 (41,6 %). Among DM patients admitted for ischemic stroke (n=85), the number of patients without lipid-lowering medication were 36 (42,4
%). When observing these numbers, it indicates that a high number of DM patients lack lipid-lowering medication. However, according to the National guidelines, not every patient with DM has an indication for lipid-lowering medication. The National Board of Health and Welfare point out that patients with DM and high or very high risk for CVD should be treated with statins in primary prevention to reduce the risk of stroke (22,43).
However, the opinion of whether all patients with DM are at high risk for CVD has been diverse (44).In previous European guidelines, all patients with type II DM were classified at high risk for CVD (45). But according to the Swedish Medical Products Agency (MPA), there is no support in that all patients over 40 with DM are at high risk for CVD (46). Furthermore, the National Board of Health and Welfare point out that
medication treatment should always be based on a combined risk factor assessment (47). As said before, among DM patients admitted for ischemic stroke, 36 patients lacked lipid-lowering medication. After risk assessments, statin treatment should be considered in at least 13 out of these 36 patients. Still, there is undertreatment, and when investigating the result of previous studies, they also indicate undertreatment of statins among patients with DM (34,35). The Swedish National Diabetes Register (NDR) as well means that there is undertreatment with lipid-lowering medication among patients with DM (48).
5.2. Strengths and limitations
One strength with this project is that possible reasons why patients with high risk for stroke lacked primary preventive medication has been considered, to make the result more reliable. Except for the baseline characteristics; medical history, age, and eGFR, CHA2DS2-VASc score, a validated risk assessment tool, was included within this study to estimate the stroke risk (49). The medical record was used to find potential
contraindications. The expected bleeding risk was assessed with HAS-BLED.
Limitations of this study also need to be addressed. The fact that this was a retrospective study mean there was no possibility of interacting with the included patients. Therefore, the patients couldn’t confirm that the medication list was correct. This could lead to an over- or underestimation of the use of stroke preventive medication. Also, there was no possibility to investigate the included patients’ adherence to the prescribed medication.
Nonadherence of anticoagulants can be a contributing factor to poor anticoagulation control with increased risk for stroke events (50,51). Furthermore, there is a risk that the collected medication lists aren’t completely correct. In COSMIC, some of the
medication lists were vague, and others not clear on what the physician had written in the medical record. However, after collecting the medication lists, it was double checked to minimize the risk of incorrect data.
5.3. Risk assessment methods
CHA2DS2-VASc and HAS-BLED were used to balance the benefit and risk of anticoagulants in AF patients admitted for stroke. CHA2DS2-VASc is a validated risk assessment tool (49), and it’s recommended to use when estimating the stroke risk in patients with AF (11). HAS-BLED has been evaluated in a Swedish study (49). The investigators concluded that HAS-BLED has a similar predictive ability compared to older bleeding risk stratification schemes (49). However, because of the similar risk factors of CHA2DS2-VASc and HAS-BLED, it was difficult to estimate the benefit-risk of anticoagulant treatment, especially in those patients who had both high CHA2DS2- VASc score and HAS-BLED score. The challenge is to manage the right balance between these risk assessment tools so that the patient gets the proper treatment.
The medical record can be used to identify patients with contraindication to certain medications. However, information explaining why the patient wasn’t on anticoagulants was often missing. Therefore, some contraindicators could have been excluded due to missing information in the medical record. Also, it was difficult finding information on why DM patients weren’t treated with lipid-lowering medication and therefore, this method was not used in these patients. Furthermore, it would have been interesting to investigate the risk factor hypertension, but because the current blood pressure could not be easily found in the medical record, it was decided not to control how well-treated this risk factor was.
In patients with DM, the stroke risk was assessed according to European guidelines, saying that statin therapy is indicated in patients with DM and IHD or documented CVD (24). This method is simplified, and other risk factors such as hypertension and smoking have not been considered in the risk assessment. Therefore, it is a risk that the number of patients indicated for lipid-lowering medication was underestimated. The most optimal strategy would have been to use the NDRs frame risk score, but due to lack of data, this method couldn’t be used.
5.4. Future directions
This study has shown the rate of prescribed anticoagulants in patients with AF and the rate of prescribed lipid-lowering medication among DM patients within the MedBridge study. It would be interesting if similar studies were made in other Swedish hospitals than the included, to be able to compare this nationally and to see if the result is generalizable to the whole population. In Riksstroke register, there is a comparison between hospitals, but the results show the rate of prescribed anticoagulants and prescribed statins among patients with ischemic stroke after discharge (29). Also, further studies should include more risk factors; for instances, the rate of prescribed antihypertensives among patient with hypertension or the rate of prescribed glucose- lowering medication among patients with DM. This could help getting insight into which part of the risk factor management and primary prevention of stroke that should be improved.
6. Conclusions
AF and DM are both common risk factors for ischemic stroke. From a total of 324 patients admitted for stroke, there was 68 with AF and 85 with DM. Of all MedBridge patients with AF, approximately one in five lacked anticoagulants, but there were only a few AF patients, out of those admitted for stroke, that lacked anticoagulants after risk assessment. However, this study indicates undertreatment with statins among patients with DM. Further studies should include more risk factors to get an insight into which part of the risk factor management and primary prevention of stroke that should be improved.
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Appendices
Appendix A: Risk assessment of AF patients admitted for ischemic stroke
Table A1. Risk assessment of AF patients, admitted for ischemic stroke, without anticoagulants.
* Medical record information from physicians, explaining why the patient doesn't have anticoagulants
** Based on the score of CHA2S2-VASc and HAS-BLED. OAC = Oral anticoagulants.
CHA2DS2-VASc: anticoagulants are recommended in men with risk score ≥2 and in women with ≥3 HAS-BLED: low bleeding risk: 0-2 scores, high bleeding risk: 3-8 scores
Patients without OAC
Age Sex (M/F)
eGFR (ml/min/1,73m2)
CHA2DS2-VASc (score)
HAS-BLED (score)
COSMIC*
OAC is indicated**
1 1917 F 45 4 2 Missing Yes
2 1935 M 53 3 2 Missing Yes
3 1931 F 59 7 3 Missing
With caution
4 1948 F 57 3 2 Missing Yes
5 1949 M 70 1 1 Missing Yes
6 1940 F 33 4 3 Missing
With caution
7 1936 M 47 4 2 Missing Yes
8 1927 M 66 2 1 Missing Yes
9 1940 M 57 6 3
Previous subdural hematoma
With caution
10 1929 F 71 7 2 Missing Yes
11 1936 F 46 4 2 Missing Yes
12 1922 F 24 5 2
Previous gastrointestinal bleeding
With caution
13 1931 F 79 3 1 Missing Yes
14 1939 F 32 7 3 Missing
With caution
Table A2. Risk assessment of AF patients, admitted for ischemic stroke, with antiplatelets
* Medical record information from physicians, explaining why the patient doesn't have anticoagulants
** Based on the score of CHA2S2-VASc and HAS-BLED. OAC = Oral anticoagulants.
CHA2DS2-VASc: anticoagulants are recommended in men with risk score ≥2 and in women with ≥3 HAS-BLED: low bleeding risk: 0-2 scores, high bleeding risk: 3-8 scores
Patients with antiplatelet
Age Sex (M/F)
eGFR (ml/min/1,73m2)
IHD CHA2DS2-VASc (score)
HAS-BLED (score)
COSMIC*
OAC is indicated**
1 1935 F 58 No 7 3 Missing
With caution
2 1933 F 62 No 4 2 Missing Yes
3 1922 F 53 Yes 4 2 Missing Yes
4 1940 M 81 No 5 4
Previous cerebral hemorrhage
With caution
5 1933 M 64 Yes 5 3
Previous bleeding caused by warfarin
With caution
6 1940 M 48 No 3 2 Missing Yes
7 1926 F 32 Yes 7 3 Missing
With caution
8 1933 F 50 No 5 2 Missing Yes
Appendix B: Risk assessment of DM patients admitted for ischemic stroke
Table B1. Risk assessment of DM patients, admitted for ischemic stroke, without lipid- lowering medication.
Patients without lipid- lowering medication
Age Medical history of IHD or CVD
High or very high risk
Statin should be considered*
1 1935 1 Yes Yes
2 1936 0 No No
3 1934 0 No No
4 1926 0 No No
5 1924 1 Yes Yes
6 1938 0 No No
7 1943 0 No No
8 1932 1 Yes Yes
9 1941 1 Yes Yes
10 1941 0 No No
11 1942 0 No No
12 1937 0 No No
13 1931 1 Yes Yes
14 1926 1 Yes Yes
15 1952 1 Yes Yes
16 1935 0 No No
17 1946 0 No No
18 1932 0 No No
19 1941 0 No No
20 1937 0 No No
21 1940 0 No No
22 1944 1 Yes Yes
23 1933 0 No No
24 1935 1 Yes Yes
25 1926 1 Yes Yes
26 1937 0 No No
27 1938 0 No No
28 1938 0 No No
29 1943 0 No No
30 1939 0 No No
31 1935 1 Yes Yes
32 1947 1 Yes Yes
33 1939 0 No No
34 1948 0 No No
35 1936 1 Yes Yes
36 1941 0 No No
* Risk assessment according to European guidelines, saying that statin therapy is indicated in patients with DM and ischemic heart disease (IHD) or documented CVD (24)
