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the Department of General Practice & Primary Care (C.R.S., P.C.H.), Foresterhill Health Centre, Westburn Road, The University of Aberdeen, UK
the Department of Clinical Pharmacology (C.W., D.W.), Grampian Universities Trust, Foresterhill, Aberdeen, UK.
Abstract
Background and Purpose— Secondary preventive measures play an important role in the reduction of stroke, the third largest cause of death in Scotland. We investigated whether sex, age, or deprivation differences existed in the secondary prevention of stroke in primary care.
Methods– A retrospective cross-sectional study using a computerized database with 61 practices (377 439 patients) to identify group differences in secondary preventive therapy between March 2003 and April 2004 for 10 076 patients with a diagnosis of any stroke.
Results— Women with any stroke were more likely than men to be prescribed a thiazide (odds ratios [OR], 1.60; 95% confidence interval [CI], 1.46 to 1.75) but less likely to be prescribed an angiotensin-converting enzyme inhibitor (OR, 0.73; 95% CI, 0.67 to 0.81). Women with ischemic stroke were less likely to receive either an antiplatelet or warfarin (OR, 0.84; 95% CI, 0.75 to 0.94) or statin therapy (OR, 0.82; 95% CI, 0.74 to 0.90) than men. Women with atrial fibrillation received less warfarin (OR, 0.62; 95% CI, 0.48 to 0.81) but more antiplatelet therapy than men (OR, 1.30; 95% CI, 1.00 to 1.68). The oldest patients (older than 75 years) with ischemic stroke received more antiplatelet therapy than the youngest patients (younger than 65 years) (OR, 1.83; 95% CI, 1.64 to 2.06). No significant differences in secondary preventative treatment across deprivation groups were found.
Conclusion— Important sex and age differences exist in the care of patients with stroke and suggest that women and the elderly need to be targeted for secondary prevention therapy.
Key Words: age anticoagulation antihypertensive agents antiplatelet drugs database epidemiology prevention sex stroke management
Introduction
Stroke is the third largest cause of death in Scotland, which has the highest mortality rates for stroke in Western Europe.1 A recent Scottish Executive report "Coronary Heart Disease and Stroke: A Strategy for Scotland" aims to reduce rates of ischemic heart and stroke disease through the adoption of a "high-risk" approach whereby key groups within the population are targeted for primary and secondary prevention.2 Blood pressure reduction is important in the secondary prevention of stroke.3 Furthermore, the PROGRESS study identified a blood pressure-lowering regimen (angiotensin-converting enzyme inhibitor and thiazide combined) that reduced the risk of further stroke in both hypertensive and nonhypertensive patients,4 a regimen that has subsequently been recommended by The United Kingdom Royal College of Physicians national clinical guidelines.5 For patients with ischemic stroke, aspirin6 and statins7 and anticoagulation therapy for patients with atrial fibrillation8 also have a proven role in secondary prevention.
There have been a number of reports of sex and age differences in the treatment of cardiovascular disease in primary care.9,10 Previous studies have also found sex differences in the treatment of stroke patients in the acute care setting, with elderly men older than 85 years found to be more likely to receive antiplatelet therapy.11 Conflicting results have been found for sex differences in the prescribing of warfarin.11,12 Among patients hospitalized for acute stroke, investigations such as brain imaging and angiography were used less often in women than men, even after allowing for age differences.13 Furthermore, women with carotid artery disease were less likely to be referred for carotid endarterectomy.13
No differences were found in the secondary preventive treatment of deprived patients after discharge from acute care,14 whereas suboptimal preventive care was found among deprived neighborhoods in another study.15
We used a population-based analysis to investigate whether sex, age, or deprivation differences exist in the secondary prevention of stroke using a Scottish family practice database.
Materials and Methods
All individuals resident in Scotland (including children) are registered with primary care, which is free at the point of contact and manages the treatment of patients once they are discharged from hospital. Access to secondary care is usually obtained through a general practitioner based within a primary care practice. Anonymized retrospective data on 377 439 patients registered with 61 practices participating in a continuous morbidity recording system in Scotland were obtained in April 2004. These practices and the patients registered with them were recruited to be broadly representative of the age/sex, urban/rural, and deprivation distribution of the Scottish population and have recorded the reason for every face-to-face doctor-patient encounter using trained entry clerks since March 1996.16 The practices record encounters as clinical diagnoses based on a mixture of general practitioner diagnosis supplemented (especially for serious conditions) by investigation and diagnostic input from specialist colleagues. The long-term nature of the database and its clinical focus ensures that initially uncertain events are confirmed or refuted over time and the diagnostic codes amended appropriately. Participating practices also routinely record repeat prescribing treatment for all patients.17,18 The Information and Statistics Division of the Scottish Executive operates a continuous quality assurance system for completeness and accuracy of diagnostic data.18
the data set, we identified all patients registered with the practices on March 31, 2004 who had ever had a computer record of transient cerebral ischemia or any stroke, including cerebral infarction and other stroke (all indicated by a Read code of G6 and below). While realizing that the Read coding for stroke includes both pathological and pathogenetic classifications, we attempted to divide such codes into hemorrhagic and nonhemorrhagic diagnoses of stroke, which would benefit from differing secondary preventive measures. To identify ischemic stroke or transient cerebral ischemia, those who had a hemorrhagic stroke (Read codes G60 and G680 [subarachnoid hemorrhage], G61 and G681 [intercerebral hemorrhage], G62 and G682 [other intercranial bleed]) were excluded. The key characteristics of all stroke patients, as of March 2004, were determined. These were sex, age (<64, 65 to 75, or 75), ever had hypercholesterolemia recorded (Read code C320 and below; yes or no), number of stroke-related comorbidities diabetes (C10 and below), hypertension (G2 and below), atrial fibrillation (G573 and below), coronary heart disease (G3 and below), heart failure (G58 and below), and peripheral vascular disease (G73 and below); 0, 1, 2 or 3+) and deprivation status based on postal code using Carstair’s DEPCAT categorization system based on indicators of poverty, such as overcrowding in households, unemployment, and the proportion of all persons in private households with no car. Deprivation quintile 1 comprises the most affluent patients and 5 comprises the most deprived.19 Use of secondary prevention treatments was assessed by determining whether between April 1, 2003 and March 31, 2004 a prescription had been issued (at least once) for a thiazide or an ACE inhibitor in patients with any stroke; antiplatelet (including aspirin, clopidogrel or dipyrimidole), warfarin, and statin therapy for patients with ischemic stroke; and for ischemic stroke patients with atrial fibrillation antiplatelet or warfarin therapy.
Statistical Analysis
Binary logistic regression was used to determine odds ratios and 95% confidence intervals for sex, age and deprivation groups receiving each type of treatment, adjusted for potential confounding by sex, age, hypercholesterolemia, number of stroke related comorbidities (excluding atrial fibrillation when examining treatment in patients with this condition), deprivation, and practice. Standardization (direct to the total practices population) was used and when appropriate, 2 tests were used for trend and were used to compare differences in the prevalence of disease. All analyses were performed using SPSS for Windows 11.0 (SPSS Inc).
The study protocol was approved by the Scientific Advisory Group of the Primary Care Clinical Informatics Unit-Research.
Results
10 076 (2.7% of all patients; 95% confidence intervals [95% CI] 2.6% to 2.7%) registered in the study practices had a computer record of any stroke and 9201 (2.4%; 95% CI, 2.3% to 2.5%) had a record of ischemic stroke. The overall age standardized prevalence of any stroke was higher in women (2.8%; 95% CI, 2.7% to 2.9%) than men (2.6%; 95% CI 2.5% to 2.7%), with male patients tending to be younger than female (mean age, 69.72 versus 72.71 years, respectively; P<0.001). Transient cerebral ischemia occurred more commonly in women than men, with cerebral infarction being more common among men (Table 1).
No significant differences were found between men and women in the recorded history of hypertension, heart failure, or in those with ischemic stroke or atrial fibrillation. However, men with stroke were more likely than women to have concurrent diabetes, peripheral vascular disease, and coronary heart disease. Male and older patients were more likely to have >3 comorbidities recorded than female and younger patients. More deprived patients were less likely than their more affluent counterparts to have multiple comorbidity (Table 2).
The age- and sex-standardized prevalence of any stroke significantly increased from 2.3% (95% CI, 2.2% to 2.4%) (n=1700) among the least deprived group (deprivation category 1) to 3.0% (95% CI, 2.8% to 3.1%) (n=1532) in the most (deprivation category 5) (P<0.001).
Prescription of Secondary Preventative Therapies
Overall, 44.5% (95% CI, 43.5% to 45.4%) of all stroke patients were prescribed a thiazide, 29.2% (95% CI, 28.3% to 30.1%) an ACE inhibitor and 19.1% (95% CI, 18.3% to 19.8%) an ACE inhibitor and a thiazide in the same year. 76.8% (95% CI, 77.5% to 79.2%) of ischemic stroke patients received either antiplatelet or warfarin therapy and 42.8% (95% CI, 41.7% to 43.8%) statin therapy. 93.0% (95% CI, 91.3% to 94.3%) of ischemic stroke patients with an additional diagnosis of atrial fibrillation were prescribed antiplatelet therapy or warfarin.
Women with any stroke were more likely than men to be prescribed a thiazide but less likely to be prescribed an ACE inhibitor even after adjustment for age, hypercholesterolemia, number of stroke-related comorbidities, deprivation, and practice (Table 3). Women with ischemic stroke were significantly less likely than men to receive antiplatelet, warfarin, or statin therapy. Women with ischemic stroke and atrial fibrillation were significantly less likely than men to be prescribed warfarin but more likely to be prescribed antiplatelet therapy.
Compared with the youngest age group, older patients with stroke were more likely to receive a thiazide and the oldest group less likely to receive an ACE inhibitor (Table 4). The oldest patients with ischemic stroke were significantly more likely to receive antiplatelet therapy, or antiplatelet or warfarin, and less likely to receive statin therapy. The oldest patients with ischemic stroke and atrial fibrillation were more likely to receive antiplatelet therapy but much less likely to be prescribed warfarin.
When comparing the care of patients from the higher deprivation categories with those in the least deprived group (quintile 1), no significant differences were observed in the provision of secondary prevention treatments (Table 5).
Discussion
This analysis of prescribing data derived from primary care practices in Scotland has revealed important sex- and age-related differences in the care of patients with stroke, but no important differences among deprivation groups.
Men with ischemic stroke were prescribed more antiplatelet therapy than women. These findings were in agreement with previous observations from a European hospital-based study.13 Whereas men may be more likely to be on antiplatelet therapy before they have a stroke because of the higher prevalence of concomitant ischemic heart disease, inequalities in the prescribing of this therapy should disappear after an ischemic stroke.1
Women with a diagnosis of atrial fibrillation received less warfarin even when age and other factors were allowed for. This finding is at variance with European and Canadian hospital stroke care studies,11,13 but in accordance with findings from a Swedish hospital-based study.12 It has been suggested that primary care physicians perceive women to have a greater potential for contraindication, no indication, or a greater chance of bleeding with warfarin therapy.20 Furthermore, with the longer life expectancy of women and the direct relationship between stroke and advanced age, in terms of severity and residual disability, older female patients will be those bearing the major burden of disease.13 No information was available in this data set on levels of compliance, which would require further study. The undertreatment of women with cardiovascular disease has been previously described as the "Yentl syndrome."21 Our results suggest that this phenomenon may also operate in patients with cerebrovascular disease.
The lower use of statins in older patients with ischemic stroke may have been caused by prescriber perceptions about these treatments being less effective or less cost-effective in this group.22 Despite such concerns, recent guidelines have stated that patients on lipid-lowering therapy should not have their drugs stopped because of age.23 Furthermore, because older patients are more likely to have more severe disease, they would be expected to benefit more from these important secondary preventive therapies. The greater use of antiplatelet treatments among older patients compared with the youngest group may be explained by some younger patients having to pay a prescription charge and so they are purchasing this medication from pharmacies without prescription.24 Information about such "over-the-counter" purchases is not recorded routinely by practices.
A notable feature of the study practices is the dedicated support provided to enter information about each patient-physician contact. Thus, once a diagnosis is made, its recording should be the same irrespective of the characteristics of the user. Although there might be systematic bias in the diagnostic labeling used, or in the ascertainment of stroke in different groups, once a diagnosis has been made, subsequent treatment should be the same irrespective of age, sex, or socioeconomic status (provided that other factors such as severity were the same). The computer systems used by the general practitioners were initially designed for repeat prescribing. Given the chronic nature of stroke, most prescriptions (98.2%) were issued as repeat prescriptions. We were unable to control directly for disease severity but could allow for a number of other confounders such as age, sex, deprivation, practice, hypercholesterolemia and number of comorbidities. Alternative explanations for the findings include differences between groups in frequency of side effects or response to therapy in the different groups. Prevalence cases of any stroke were examined, because it could be argued that every patient experiencing this condition should be offered secondary prevention treatment regardless of when the event occurred. Furthermore, events occurring in the more distant past are more likely to be followed-up by primary care. In addition, use of prevalent cases has enabled us to have many more events in the analysis, increasing the power of the study to detect differences that might exist.
Although epidemiological and clinical research has investigated sex differences in stroke occurrence, associated mortality, and drug effectiveness, little is known about patterns of secondary prevention treatment between groups. Our results suggest that women and the elderly need to be targeted for secondary prevention therapy so that they benefit fully from such measures. Further epidemiological and sociological studies investigating the reasons for the differing management of stroke are required.
Acknowledgments
This work was funded by Chest, Heart, and Stroke, Scotland. The authors thank the Information and Statistics Division of the Scottish Executive. The authors are grateful to the general practitioners who provided practice data to the Primary Care Clinical Informatics Research Unit.
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