J Reid, M-J MacLeod, D Williams
Aberdeen Royal Infirmary, Foresterhill, Aberdeen
Correspondence to: Dr John Reid, Ward 40, Aberdeen Royal Infirmary, Forresterhill, Aberdeen, AB25 2ZN. Tel : 01224 553449. Fax: 01224 551188 Email: johnmreid@doctors.org.uk
SMJ 2005 50(2): 69-72
Background: We aimed to study the timing of aspirin prescription in ischaemic stroke comparing patients admitted to an acute stroke unit (ASU) directly or via a general medical ward. We also analysed prescription of secondary preventive therapies in stroke patients in an ASU. Methods: Retrospective analysis was made of medical notes and prescription records of 69 patients admitted to an ASU over a three month period to establish timing of aspirin prescription with respect to onset of stroke symptoms, CT brain scan and route of admission to the ASU. Results: CT brain scans were obtained at a median of 2.1 days post stroke (IQ range 1.3-4.3). Patients directly admitted to the ASU received aspirin earlier post admission compared to those admitted via a medical ward (0.7 vs 2.2 days, p<0.01) and were also more likely to receive aspirin prior to CT scan being performed (57% vs 19%, p=0.02). 86% of stroke patients were discharged on an antiplatelet therapy, 79% on a statin, 37% on a thiazide diuretic and 32% on an ACE inhibitor or angiotensin II antagonist. Conclusion: Aspirin was given more promptly in acute stroke and more commonly prior to CT scanning in an ASU compared to a medical ward. Statin therapy is used extensively in stroke but there is a much lower rate of initiation of other secondary preventive therapies (e.g. anti-hypertensive therapy) in hospital. These findings demonstrate a hesitancy in early use of aspirin amongst general physicians and lends support for the use of stroke units.
Keywords: Stroke, aspirin, CT scan, secondary prevention.
Aspirin has been shown to be of proven benefit in acute ischaemic stroke1,2 giving rise to a modest reduction in death and dependence (13 fewer dead or dependent per 10003-5) when given within 48 hours of stroke onset. Current guidelines advise that aspirin be given promptly in ischaemic stroke1,6 and if CT scanning is not available within the first 48 hours aspirin should not be withheld in suspected acute ischaemic stroke.6,7
Giving aspirin is not associated with increased intracerebral haemorrhage2 and a meta-analysis of two randomised control trials found that acute stroke patients given aspirin who were subsequently found to have a haemorrhagic rather than an ischaemic stroke had the same outcomes as patients given placebo.2,8 Furthermore, in terms of secondary prevention, trials have shown that patients with ischaemic stroke should be considered for lipid lowering therapy with statins, blood pressure reduction for example with angiotensin converting enzyme (ACE) inhibitors plus a thiazide diuretic as well as anti-platelet therapy.3,9-12
Stroke units have been shown to improve outcome for stroke patients.13 The reasons for this benefit are not established but may include a number of factors such as better adherence to stroke protocols and coordinated multidisciplinary care.
We examined the timing of aspirin prescription in acute stroke with respect to the time from symptom onset and CT scan to determine whether there was a difference between patients admitted to a stroke unit directly or to a medical ward before transfer to a stroke unit. We also examined use of secondary preventive therapies in an acute stroke unit.
Retrospective analysis was made of patients’ casenotes who were admitted to the Acute Stroke Unit (ASU) at Aberdeen Royal Infirmary during a three month period (December 2002-February 2003). Patients are admitted to the ASU following referral to a 24 hour on-call pager held by a stroke physician. Referrals are received from general practitioners, from within the hospital (e.g. Accident and Emergency, Medical and Surgical wards) or regional community hospitals. Patients are either directly admitted to the ASU if a bed is available or are admitted to a general medical ward if no bed is available and are transferred to the ASU when a bed becomes available.
The ASU is a 21 bed unit covering a population of 523,000 in the North East of Scotland and 42,000 in Orkney and the Shetland Isles, and annually admits approximately 300 patients. Guidelines for management of acute stroke are available on both the medical and ASU wards.
Clinical details, risk factors for stroke and relevant medications on admission to the ASU were obtained from the hospital notes and from a proforma recorded for each patient discharged which is held on a database. A diagnosis of atrial fibrillation or left ventricular hypertrophy was ascertained from analysis of the ECG on admission using Sokolow-Lyon criteria.14 The timing of initiating drug therapies was found from the prescription records. Patients with an indeterminate onset of symptoms were excluded from analyses of timing post onset of symptoms. Timing of aspirin prescription could not be established in one patient because the prescription record could not been found in the casenotes. The data are either presented as median plus interquartile range if the data was not normally distributed or as mean +/-standard deviation where stated. ÷2, students t-test and 2 sample Mann Whitney statistical tests were performed where appropriate. Significance was taken as p<0.05.
A total of 69 patients were admitted to the ASU over a three month period (M:F ratio of 51:49, mean age 64.3+/ -12.4 and 76.0+/-9.7 years respectively). The prevalence of risk factors for stroke on admission were; hypertension 58%, previous stroke 28%, smoking 27%, ischaemic heart disease 22%, left ventricular hypertrophy 18%, diabetes 16%, atrial fibrillation 15% and peripheral vascular disease 12%. The median length of stay in the ASU was eight days (3-18). The mean systolic and diastolic blood pressure on admission was 160+/-26 and 84+/-14 mmHg respectively. Six of the 69 patients died following stroke on the ASU.
Type of stroke
Stroke was classified clinically using the Oxford stroke classification:15 the majority of strokes (85%) were anterior circulation strokes (33% partial, 30% lacunar, 22% total), with 12% posterior circulation strokes, 3% transient ischaemic attacks and one amaurosis fugax. 59% of the anterior circulation strokes affected the left hemisphere. CT scans were performed in 66/69 patients. Radiologically the strokes were classified as 36 new infarcts, nine multiple infarcts, seven old infarcts, five primary intracerebral haemorrhages, three haemorrhagic infarcts and six normal. There were no subdural or extradural haematomas identified.
Patients admitted on anti-platelet and anticoagulant therapy
Of the 69 patients, 29 were taking anti-platelet therapy (APT) on admission (24 aspirin alone, two clopidogrel alone, two aspirin and dipyridamole and one aspirin and clopidogrel). Of these 29, 14 had APT continued whilst 15 had it stopped on admission. The reasons given for withholding APT were; no reason documented (7), low Glasgow Coma Scale (GCS) score (2), severe stroke (2), haemorrhage thought likely (1), headache (1), heartburn (1) or considering warfarin for paroxysmal AF (1). Nine of these 15 were subsequently restarted on aspirin some time later (see Fig. 1).
There was a significant trend for patients admitted on APT to have it stopped in hospital if they were first admitted to a medical ward (12/19=63%) compared to direct admissions to the ASU (1/7=14%, p=0.027, ÷2 test). All six patients admitted on warfarin had this initially withheld pending CT scan. Two of these patients had aspirin initiated and all six were subsequently restarted on warfarin (all non-haemorrhagic infarcts). Two patients with recurrent stroke on aspirin were additionally prescribed dipyridamole.
Patients started on aspirin as an acute treatment for stroke
Of the 40 patients not on APT on admission 33 were given aspirin acutely for stroke. This included two patients admitted on warfarin that was stopped and aspirin started. Including the nine patients who had aspirin stopped on admission and then restarted, there were a total of 42 patients who received aspirin as an acute treatment of stroke (see Fig. 1).
Timing of aspirin
Eighty-seven per cent of patients had a definite time of onset of symptoms, and of these 23% were admitted within 0-3 hours and 27% between 3-6 hours of stroke onset. Patients were admitted to hospital a median of 6.4 hours (3.6-24) post onset of stroke symptoms. 3.5% of patients had a CT scan within six hours of symptom onset. The median time to CT scanning of patients was 2.1 days (1.3-4.3) post symptom onset of stroke and 1.4 days (0.8-2.8) post admission to hospital. CT scans tended to be obtained more urgently (median of 0.6 days, 0.1-0.8) post admission to hospital in the six patients who were taking warfarin on admission.
Of the 42 patients given aspirin as an acute treatment, the median time to receive aspirin was 2.7 (0.8-3.6) days post symptom onset, 1.7 (0.4-2.8) days post admission to hospital and 0.7 days (-1.0 to 1.7) post CT scan. Only one patient given aspirin prior to CT scan was found to have a haemorrhagic stroke and the aspirin was subsequently stopped.
Comparison of direct admission to ASU with admission via a medical unit on timing of aspirin
Fifty-two per cent of patients were admitted first to a general medical ward and transferred to the ASU after a median of 1.5 days (1.0-3.7). Thirty-eight per cent of patients were admitted directly to the ASU, 4% were admitted from peripheral hospitals, 4% from neurosurgery and 2% from general surgery.
In patients given aspirin as an acute treatment, aspirin was given significantly earlier both after onset of stroke (1.3 vs 3.0 days, p<0.025) and following hospital admission (0.7 vs 2.2 days, p<0.01) in patients directly admitted to the ASU compared to those admitted via a general medical ward (Table I, Fig. 2). Aspirin was also given as an acute treatment within 48 hours of symptom onset in 10/16 (63%) patients admitted directly to the ASU compared to 6/20 (30%) admitted via the general medical ward (p=0.051, NS, ÷2 test, Table I).
A significantly higher proportion of patients (8/14 or 57%) directly admitted to the ASU compared to those admitted first to a general medical ward (4/21 or 19%) were given aspirin prior to CT scan (p=0.02, ÷2 test, Fig. 3). Comparing patients admitted directly to the ASU with those admitted via a medical ward there was no difference in age, blood pressure, GCS, time to admission from symptom onset or time to CT scan from admission (TableII).
Secondary preventative therapies
The percentage of all stroke patients taking ACE inhibitors, angiotensin II (AII) antagonists, thiazide diuretics and statins on admission and at discharge are shown in Table III. Ten per cent of patients had an ACE inhibitor prescribed and 18% had a thiazide diuretic prescribed as new therapies whilst in hospital.
There was no difference in age or severity of stroke in patients prescribed new anti-hypertensive treatments on the ASU compared to those who were not (75% vs 67% were transient ischaemic attacks, partial or lacunar anterior circulation strokes respectively). However, the average blood pressure on admission was higher in patients who were commenced on ACE inhibitors or thiazide diuretics as a new treatment compared to patients not started on these anti-hypertensive therapies (175/94 vs 145/77, p<0.05 for systolic and diastolic blood pressure, students t-test).
Our results have demonstrated a significant delay in aspirin prescription for stroke patients admitted to a medical ward compared to direct admission to a stroke unit. There was also a significantly higher proportion of stroke patients being prescribed aspirin prior to CT scan and a significant tendency to continue APT in acute stroke patients admitted directly to a stroke unit compared to patients admitted via a medical ward.
The reasons for the delay in aspirin use in stroke on general medical wards compared to an ASU may derive from poor knowledge of current guidelines on treatment of acute stroke, despite their availability. These guidelines highlight that aspirin should be given within 48 hours of stroke onset and that aspirin should not be delayed if a CT scan is awaited and an ischaemic stroke is thought likely. 2,6,7,16 Furthermore, studies have shown that aspirin is not associated with increased mortality if it is given for a presumed ischaemic stroke that turns out to be haemorrhagic. 2,8
A recent meta-analysis of aspirin given inadvertently for presumed ischaemic stroke that was later found to be a haemorrhagic stroke found that the odds ratio for death for patients given aspirin compared to placebo was 0.96 (95% CI 0.62-1.5) and for death or dependence was 0.68 (95% CI 0.46-1.02) 17. The confidence intervals for the odds ratio for death are wide and so might include the possibility of an adverse effect. The majority of the patients in this review only received a few doses of APT, and therefore the apparent safety of aspirin given inadvertently in haemorrhagic stroke may not continue if aspirin is given for a prolonged period. It is acknowledged however that advice to give aspirin in suspected ischaemic stroke prior to a CT scan may not be universally accepted.17 Further, it is not clear whether a delay in giving aspirin of more than 24 hours as seen in this study comparing the two admission routes to the ASU would alter the benefit of aspirin in stroke.
A previous questionnaire of medical consultants’ attitudes to use of aspirin in stroke in the UK showed that the majority would initiate aspirin treatment within 48 hours of symptom onset and only 10% would withhold aspirin until the CT result was known.18 The more prompt use of aspirin in an ASU is more in keeping with current guidelines1,2,6,7,16 and lends support to the finding that stroke units benefit stroke patients.13It is acknowledged that a median time to CT scan post stroke onset of 2.1 days is not ideal and guidelines advise CT scanning within 48 hours of stroke.16 Further, the difference in timing of aspirin with respect to CT scan in stroke observed in this study might not arise if there were a more rapid access to cranial imaging. Sixty-five per cent of centres in Scotland perform CT brain scans within 48 hours of stroke onset.17 A recent study also modelled the cost effectiveness of different CT scanning strategies in stroke and concluded that the most cost-effective strategy is to scan all strokes immediately.17 Twenty-three per cent and 50% of patients were admitted within three and six hours of onset of stroke symptoms. These times are similar to those seen in a study in the UK and Ireland (37% within three hours, and 50% within six hours).19 The lower admission rate (23% vs 37%) within the first three hours may reflect the higher rural population in the North East of Scotland.
Prescription rates on discharge from ASU show that 79% were on a statin, 37% on a thiazide diuretic, and 32% on an ACE inhibitor or AII antagonist. Statins and thiazide diuretics were prescribed at a median of three and six days respectively post symptom onset, whereas ACE inhibitors and/or AII antagonists were prescribed at a median of eight days post symptom onset. There is debate over whether anti-hypertensive therapy can be initiated post stroke in selected patients in hospital or should be initiated at a follow-up stroke clinic.16 The patients in this study who were given additional antihypertensive therapy (e.g. ACE inhibitors and thiazide diuretics) in hospital post stroke tended to be more hypertensive on admission. A recent phase II trial investigating use of an angiotensin II antagonist within seven days of onset of stroke showed a beneficial effect on mortality in stroke compared to placebo.20
A recent review of practise at a hospital based TIA clinic in Scotland showed higher initiation rates of 55-70% for statins, ACE inhibitors and diuretics, although admittedly this is a different group from acute stroke patients.21 The lower prescription of thiazide diuretics and ACE inhibitors may represent a missed opportunity to initiate secondary preventive therapies.
In summary we found that aspirin is prescribed earlier in hospital, and more frequently prior to CT scan if patients are admitted directly to a stroke unit compared to admission via a general medical ward. This demonstrates that stroke units adhere to current stroke guidelines and this may partly explain why stroke units benefit stroke patients1. In the UK a minority of stroke patients are cared for on stroke units22,23 and the results of this study lend support for increased use of stroke units and better dissemination of current guidelines for aspirin use in stroke.
ACKNOWLEDGEMENTS: Thanks to Elaine Horne for help with the data collection.
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