de Weerd et al.

BMC Family Practice 2013, 14:74

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RESEARCH ARTICLE Open Access

Survival of stroke patients after introduction

of the ‘Dutch Transmural Protocol TIA/CVA’
Leonie de Weerd*, Feikje Groenhof, Boudewijn J Kollen and Klaas van der Meer

Abstract
Background: Earlier research showed that healthcare in stroke could be better organized, aiming for improved
survival and less comorbidity. Therefore, in 2004 the Dutch College of General Practitioners (NHG) and the Dutch
Association of Neurology (NVN) introduced the ‘Dutch Transmural Protocol TIA/CVA’ (the LTA) to improve survival,
minimize the risk of stroke recurrence, and increase quality of life after stroke. This study examines whether survival
improved after implementation of the new protocol, and whether there was an increase in contacts with the
general practitioner (GP)/nurse practitioner, registration of comorbidity and prescription of medication.
Methods: From the primary care database of the Registration Network Groningen (RNG) two cohorts were composed:
one cohort compiled before and one after introduction of the LTA. Cohort 1 (n = 131, first stroke 2001–2002) was
compared with cohort 2 (n = 132, first stroke 2005–2006) with regard to survival and the secondary outcomes.
Results: Comparison of the two cohorts showed no significant improvement in survival. In cohort 2, the number of
contacts with the GP was significantly lower and with the nurse practitioner significantly higher, compared with cohort
1. All risk factors for stroke were more prevalent in cohort 2, but were only significant for hypercholesterolemia. In both
cohorts more medication was prescribed after stroke, whereas ACE inhibitors were prescribed more frequently only in
cohort 2.
Conclusion: No major changes in survival and secondary outcomes were apparent after introduction of the LTA.
Although, there was a small improvement in secondary prevention, this study shows that optimal treatment after
introduction of the LTA has not yet been achieved.
Keywords: Stroke, Survival, General practice, Healthcare, Prevention

Background Studies have shown that healthcare in stroke patients

The prevalence of stroke in general practice in the could be better organized, that more thrombolysis
Netherlands is 13.3 in 1000 men and 13.4 in 1000 treatment should be given and that more admissions
women [1]. Additionally, within 5 years after stroke, 50% to a stroke unit would result in better survival and less
of patients will die and 30-50% will experience another comorbidity [6-9]. It became increasingly obvious that
stroke [2]. secondary prevention (e.g. controlling blood pressure,
A stroke has considerable impact on the patient’s life cholesterol and glucose) is also very important. Treatment
and his/her family [2,3]. Stroke can cause various of cardiovascular/cerebrovascular risk factors reduces the
neurological deficits, including paralysis, loss of vision, risk of stroke, in particular hypertensive treatment.
aphasia, spatial disorder, disturbance in thinking, difficulty Moreover, consistent measurements to control whether
in swallowing and incontinence [4]. Moreover, stroke has treatment is effective are essential in stroke prevention
cognitive, behavioral, emotional and social consequences programs [10]. All these findings emphasized that specific
[5] and, in the chronic phase, negatively affects quality of treatment is required for stroke patients.
life [3,4]. A transmural stroke service, in which neurologists and
general practitioners (GPs) participate, would allow
* Correspondence: [email protected] proper care to be delivered in the appropriate setting.
Department of General Practice, University of Groningen, University Medical
Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Patients should be quickly referred to the hospital and
Netherlands

© 2013 de Weerd et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
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the GP is responsible for secondary prevention at home After discharge from hospital, the GP continues this
[11]. To improve survival after stroke and minimize the treatment.
risk of stroke recurrence, the Dutch College of General Antihypertensive medication is prescribed to patients
Practitioners (NHG) and the Dutch Association of with hypertension 2 weeks after the patient has stabilized.
Neurology (NVN) introduced the ‘Dutch Transmural The protocol advises the prescription of statins to patients
Protocol TIA/CVA’ (the LTA) in 2004 [12]. It also offers with a total cholesterol of 3.5 mmol/L or higher [12]. For
the GP and neurologist the advice to provide quality treatment of high glucose levels, the NHG protocol
healthcare at the right time, without compromising the ‘Diabetes mellitus type 2’ must be followed [13]. Health
continuity of care. education should be performed by a neurologist, but the
The LTA protocol states that when acute neurological GP should also discuss risk factors, lifestyle changes and
symptoms are apparent, the GP should visit the patient use of medication with the patient. This is important
immediately so that thrombolytic treatment can be because patients regard the GP and neurologist as their
given within 3 hours after the symptoms started. Other main source of information [12,14,15].
indications for an emergency visit are unconsciousness, GPs are responsible for assisting in the coordination of
worsening of neurological symptoms, or when the event rehabilitation and post-hospital care of patients at home.
is so worrying for the patient or his/her environment The neurologist has to provide a discharge letter with
that delay is not justified. Visiting the patient at home treatment advice and a risk profile within 1 week after
can be postponed if the situation is stable and no discharge from hospital to ensure that quality aftercare
thrombolysis is possible [12]. is possible [12,15].
The protocol recommends that agreements should be The purpose of this study is to compare the survival
made about healthcare between the local hospital and of patients one year after stroke before and after the
GPs. In general, when a GP suspects an ischemic stroke, introduction of the LTA. We were not interested in
treatment with a platelet inhibitor or a coumarin establishing a causal relationship in survival before and
derivative is started the same day and patients are after stroke due to the introduction of LTA, but only to
admitted to a hospital (preferably a stroke unit). The show changes in survival occurring between pre- and
protocol states that the neurologist is responsible for post LTA time periods. We expected survival to be better in
the remaining necessary medication, and for starting stroke patients after the introduction of the LTA, because
rehabilitation and secondary prevention in hospital. follow-up and secondary prevention is implemented more

Table 1 Baseline characteristics of the study population

Variables Cohort 1 (%) Cohort 2 (%) p-value
Patients included 131 132
Gender
- Men 72 (55) 59 (45) 0.096*
- Women 59 (45) 73 (55)
Age, in years: average [range] 69.82 [19–105] 70.86 [31–103] 0.565†
Risk factors present before stroke/History
- K85 (high blood pressure without hypertension) 8 (6) 9 (7) 0.815*
- K86/87 (hypertension) 34 (26) 31 (23) 0.643*
- T93 (hypercholesterolemia) 2 (2) 3 (2) 0.658*
- T90 (diabetes) 17 (13) 16 (12) 0.834*
- K91 (arteriosclerosis) 2 (2) 1 (1) 0.557*
- K89 (TIA) 5 (4) 9 (7) 0.278*
Average number of contacts (consults and visits) with general practice in the year preceding stroke
- Contact moments GP 5.40 5.76 0.914‡
- Consult GP 3.48 5.76 0.346‡
- Visits GP 2.46 3.17 0.811‡
- Contacts nurse practitioner 1.00 1.01 0.319‡
Average exposure time§ in days 528 554 0.256‡
*Pearson’s Chi-square test, †Independent T-test, ‡ Mann–Whitney test. Exposure time: time during which patients were registered in a general practice during
§

the study.
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regularly when complying more strictly with the LTA.

Secondary outcomes include survival at 2-year follow-up,
difference in the number of contacts with the GP/nurse
practitioner, and difference in secondary prevention
(e.g. prescription of medication, comorbidity, risk factors).
We expected the number of contacts with the GP and the
prescription of medication and comorbidities to be higher,
because the LTA recommends that GPs check and monitor
patients more regularly after stroke.

Methods
Study design and setting
In this registry study, the database of the Registration
Network Groningen (RNG) was used. This primary
care-based network was established in 1989, and consists
of three group practices in the northern part of the
Netherlands with about 20 GPs and about 30,000 patients
[16]. The RNG is a validated register [17]. All contacts,
diagnoses, referrals and prescriptions are registered in the Figure 1 Survival at one-year follow-up.
RNG using the International Classification of Primary
Care (ICPC) [18]. Anonymous patient data were used Results
according to the privacy assignments by the RNG. The Baseline characteristics
study was in agreement with the regulations for publication A total of 263 patients were included: 131 patients in cohort
of patient data and, therefore, no further approval was 1 (first stroke 2000–2001) and 132 patients in cohort 2
required from the Medical Ethical Committees of the (first stroke 2005–2006). Table 1 provides details on
University Medical Centre Groningen. baseline characteristics: there were no significant differences
between the two groups.
Participants and data collection
The study includes two cohorts of patients, one cohort
Survival
compiled before and one after introduction of the LTA.
Inclusion criteria were patients who had a first stroke in Both cohorts were followed for two years, during which
2000–2001 (cohort 1) and in 2005–2006 (cohort 2). These time some patients died. There was no significant
patients had to be registered in the general practice for at
least one year and were followed for two years after stroke.
No additional selection criteria were applied. A total of
263 patients were included. Details on history, risk factors,
mortality, morbidity, medication and referrals were obtained
from the RNG.

Statistical analysis
For statistical analysis SPSS 15 for Windows (SPSS Inc.,
Chicago) was used. Statistical significance was set at
p < 0.05 (two-sided). To test differences between groups
the Student’s t-test was used for normal distributed
(continuous) variables and the Mann–Whitney U test
was used for not normal distributed continuous, ordinal
scaled or count variables. The Chi-square test was used
for independent observations of nominal or dichotomous
variables. The Kaplan-Meier method was used to estimate
the survival distributions and the log-rank test was
used to compare differences in survival between the
Figure 2 Survival at two-year follow-up.
groups [19,20].
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Table 2 Number (%) of deceased patients during the Secondary prevention

two-year follow-up Theoretically, the LTA should lead to an increase in
Deceased Cohort 1 (%) Cohort 2 (%) p-value# the number of ICPC codes in cohort 2 compared to
Men cohort 1 (Table 4). Table 4 shows that all ICPC
- related to stroke* 8 (11) 6 (10) 0.862 codes are more frequently applied in cohort 2 than
in cohort 1; however, the difference is significant
- within one year 17 (24) 14 (24) 0.987
only for hypercholesterolemia.
- within two years 24 (33) 18 (31) 0.730
Women Medication
- related to stroke* 6 (10) 6 (8) 0.698 With the introduction of the new protocol more attention
- within one year 20 (34) 18 (25) 0.244 is paid to secondary prevention and the prescription of
- within two years 25 (42) 20 (27) 0.071 medication, e.g. aspirin and statins. Table 5 presents data
on the number of patients who were prescribed several
0-60 years
types of medication in the year preceding the stroke and
- related to stroke* 4 (3) 2 (2) 0.523
in the following two years post stroke.
- within one year 4 (3) 2 (2) 0.523 The results show that in both cohorts significantly more
- within two years 5 (4) 3 (2) 0.619 cholesterol-lowering medication and antithrombotics were
0-80 years prescribed after stroke. Also, only in cohort 2 significantly
- related to stroke* 10 (8) 6 (5) 0.306 more medication affecting the renin-angiotensin system
was prescribed after stroke.
- within one year 21 (16) 15 (11) 0.280
- within two years 27 (21) 17 (13) 0.091
Discussion
Deceased related to stroke 14 (11) 12 (9) 0.665 This study examined whether the survival of stroke
Deceased during one-year 37 (28) 32 (24) 0.461 patients changed after the introduction of the ‘Dutch
follow-up Transmural Protocol TIA/CVA’ , and whether the number
Deceased during two-year 49 (37) 38 (29) 0.138 of contacts with the GP/nurse practitioner, registration
follow-up
of comorbidity, and prescription rate of medication
*Related to first stroke: death within 3 days. #Pearson’s Chi-square test.
increased.
The two cohorts were well matched regarding the
difference in survival between the two cohorts at one-year number of patients, age, gender and comorbidity.
follow-up (p = 0.511) (Figure 1) or at two-year follow-up After introduction of the LTA there was no significant
(Figure 2) (p = 0.188). difference in survival between cohort 1 and 2. We
Table 2 shows the percentage of patients that died in expected survival to improve after introduction of the
both cohorts. In cohort 1 more men and women died than LTA because the GPs could use the FAST test, i.e. a
in cohort 2; however, the difference is not significant. In checklist in which patients are sent to hospital directly
both cohorts more patients died with increasing age. after telephone contact without causing any delay [12,21].
An explanation for this result might simply be that the
LTA does not lead to improved survival, despite rapid and
Healthcare in general practice effective patient care. Another possibility is that the situ-
For healthcare consumption of patients in general practice, ation envisaged with the LTA was not achieved, perhaps
a distinction was made between the consults and visits due to problems associated with the implementation of
with the GP and/or nurse practitioner. There were no thrombolysis and stroke unit treatment [22,23].
significant differences between healthcare consumption of Although survival is slightly better in cohort 2 (Figures 1
the two cohorts with the exception of the average number and 2), our results show that there was no significant
of contacts with the nurse practitioner (Table 3). improvement in long-term survival after introduction of

Table 3 Healthcare provided by general practice during two-year follow-up

Variables Cohort 1 (range) Cohort 2 (range) p-value#
Median number of contacts with GP (consults/visits) per patient per year 8.0 (0–44) 7.0 (0–36) 0.801
Median number of consults per patient per year 2.0 (0–31) 2.0 (0–30) 0.746
Median number of home visits per patient per year 2.0 (0–33) 1.0 (0–30) 0.230
Median number of contacts with nurse practitioner per patients per year 0.0 0.0 (0–17) <0.001
#
Mann–Whitney test.
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Table 4 Number (%) of patients with different risk factors According to the LTA, secondary prevention in stroke
included in the prescription register and/or journal two patients is important, especially for the GP [12]. This
years after stroke should lead to an increase in the number of risk factors in
ICPC Cohort 1 (%) Cohort 2 (%) p-value* cohort 2 compared to cohort 1. The data indeed showed
K85 (high blood pressure 3 (2.3) 8 (6.1) 0.127 an increase, but only the increase of hypercholesterolemia
without hypertension) is significant; this might be because (in 2003) treatment of
K86/87 (hypertension) 54 (41.2) 63 (47.7) 0.288 stroke patients (without elevated cholesterol) with statins
T93 (hypercholesterolemia) 24 (18.3) 45 (34.1) 0.004 proved to be effective [12,27]. However, whether secondary
T90 (diabetes) 26 (19.8) 31 (23.5) 0.474 prevention has in fact improved remains debatable. A
future questionnaire study among GPs and patients
K91 (arteriosclerosis) 1 (0.8) 2 (1.5) 0.566
*
might provide more insight into secondary prevention
Pearson’s Chi-square test.
after implementation of the LTA.
Implementation of the LTA was expected to increase
the LTA; a longer follow-up period might perhaps reveal use of medication to treat risk factors. The increase in
a significant difference as both curves tend to diverge prescription rate of certain types of medication is not
progressively over time. per se due to the introduction of the LTA, but also
The number of patient contacts in general practice because of new insights into drug use. In both cohorts
was expected to increase after introduction of the LTA, almost all medication is prescribed more frequently after
because the LTA recommends GPs to aim for intensive stroke than before stroke. However, only for cholesterol-
rehabilitation and to monitor secondary prevention in lowering medication and antithrombotic medication is
stroke patients [12]. This should lead to an increase in this increase significant. The increase in use of statins is
the number of GP contacts, especially in the first year probably because they are known to be effective in stroke
after stroke. There was a slight increase in contacts with patients, regardless of cholesterol levels [27]. Furthermore,
the nurse practitioner, a nurse practitioner assists the GP significantly more ACE inhibitors are prescribed after
in care for chronic patients [24], including stroke patients. stroke in cohort 2; this might be because ACE inhibi-
This might be explained by the recent introduction of tors are known to very effective in the treatment of
nurse practitioners for cardiovascular risk management in hypertension [28].
GP offices. Although there was an increase in contacts Overall, this study showed only minimal differences
with the nurse practitioner this was not the case for the between cohort 1 and 2. A possible reason for this is that
number of GP contacts and visits. A possible explanation there were no major differences in the groups before
is the establishment of GP centers, which probably means introduction of the LTA. Another explanation could be
that visits by the GP in the evenings/weekends are no that there was already a shift in the referral and treatment
longer necessary [25]. Moreover, there is a tendency patterns in stroke.
towards more telephone contacts and fewer home visits This study has several limitations. The study popula-
[26]. Another explanation is that insufficient attention tion was selected from general practices in the northern
is paid to rehabilitation by GPs, implying the stricter part of the Netherlands. To be more representative, the
implementation of the LTA may still be beneficial. Expos- study group should be selected from multiple general
ure time (defined as number of days during which patients practices throughout the Netherlands.
were registered in a general practice) was the same in Furthermore, this registry study and its design were
both groups. not suitable to examine a causal relationship between the

Table 5 Number of patients who were prescribed several types of medicine from one year before stroke (Before) until
two years post stroke (After)
Medication Number of patients in Cohort 1 (%) Number of patients in Cohort 2 (%)
Before After p-value* Before After p-value*
Antithrombotics 50 (38.2) 85 (64.9) <0.001 56 (42.4) 103 (78.0) <0.001
Diuretics 55 (33.6) 36 (27.5) 0.165 47 (35.6) 49 (37.1) 0.798
Beta-receptor blocker 35 (26.7) 46 (35.1) 0.120 49 (37.1) 48 (36.4) 0.898
Calcium channel blocker 14 (10.7) 21 (16.0) 0.116 18 (13.6) 13 (9.8) 0.339
Medication influencing renin-angiotensin system 20 (15.3) 30 (22.9) 0.243 40 (30.3) 58 (43.9) 0.022
Antidiabetics 20 (15.3) 19 (14.5) 0.964 24 (18.2) 28 (21.2) 0.536
Cholesterol-lowering medication 15 (11.5) 23 (17.6) 0.035 39 (29.5) 68 (51.5) <0.001
*
Pearson’s Chi-square test.
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doi:10.1186/1471-2296-14-74
Cite this article as: de Weerd et al.: Survival of stroke patients after
introduction of the ‘Dutch Transmural Protocol TIA/CVA’. BMC Family
Practice 2013 14:74.

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