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(Stroke. 2004;35:913.)
© 2004 American Heart Association, Inc.
Original Contributions |
From 2nd Section of Internal Medicine (S.V., C.M., A.B., M.R., A.R.A., R.F., G.Z.), Department of Clinical and Experimental Medicine, University of Ferrara, Italy; and Geriatric Section (L.J.D., M.B.), Department of Emergent Pathologies, University of Palermo, Italy.
Correspondence to Dr Stefano Volpato, Department of Clinical and Experimental Medicine, University of Ferrara, Via Savonarola, 9, I-44100 Ferrara, Italy. E-mail vlt{at}unife.it
| Abstract |
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Methods A total of 17 337 patients admitted to geriatric and internal medicine wards participating in the study in the 1993 to 1998 survey period were analyzed. Patients with coded diagnoses of ischemic stroke and transient ischemic attack (TIA) were selected. Data recorded included demographic and clinical characteristics and medication prescription during hospital stay and at discharge. Logistic regression analyses were used to identify conditions associated with the prescription of antiplatelet or anticoagulant drugs.
Results Among 946 patients with diagnosis of stroke or TIA (mean age 78 years), >40% was discharged without antithrombotic prescription. Conditions that made the prescription more unlikely were diagnosis of stroke (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.44 to 0.86), presence of anemia (OR: 0.70; 95% CI: 0.49 to 0.98), severe disability (OR: 0.48; 95% CI: 0.30 to 0.75), and cognitive impairment (OR: 0.58; 95% CI: 0.43 to 0.75). There was an independent and additive association of physical and cognitive status with antithrombotic therapy prescription.
Conclusions A high rate of patients affected by stroke or TIA are discharged from the hospital without antithrombotic therapy. The most important correlates of the likelihood of not receiving an antithrombotic medication were cognitive and functional status.
Key Words: antithrombotic therapy stroke aging epidemiology
| Introduction |
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10% in the first year and
5% per year thereafter.3 Stroke recurrence increases mortality, disability, institutionalization, and may lead to cognitive impairment and dementia.4 Despite recent advances in the treatment of acute ischemic stroke, the number of effective and feasible treatments remains limited.5,6 For this reason, prevention of ischemic stroke, particularly secondary prevention, is a major clinical and public health issue.7 The efficacy of antiplatelet and oral anticoagulant therapy in stroke prevention has been clearly demonstrated by several clinical trials8,9; conversely, few data exist regarding the actual prescription of secondary prevention treatment in clinical practice, and some studies highlighted inadequate management of patients with previous stroke or TIA.10,11
The aim of this study was to describe the prescription of antiplatelet and oral anticoagulant therapy in patients hospitalized for an acute ischemic stroke or TIA. In addition, we sought to identify demographic and clinical factors that may affect this type of prescription at discharge from the hospital.
| Materials and Methods |
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For this project, only patients enrolled during 1993, 1995, 1997, and 1998 surveys were considered. Data collected in 1988 and 1991 were not included because most of the randomized clinical trials showing the protective effect of antithrombotic therapy were published in the 1990s.8 Moreover, according to the anatomical therapeutic chemical classification, acetyl salicylic acid was not classified as an antiplatelet drug until 1993. Therefore, our study population was limited to 17 337 patients enrolled in the 1993 to 1998 period. Of them, 946 who had a main discharge diagnosis of ischemic stroke or TIA represent the final sample.
Prevalent Disease Ascertainments
All diseases diagnosed by the physicians were classified according to the International Classification of Disease, 9th revision (ICD-9). Cases of ischemic stroke and TIA were identified on the basis of the ICD-9 code (434 to 434.9, 436, 433.01, and 435 to 435.9, respectively). In addition, the following diseases were considered: hypertension, atrial fibrillation, diabetes, congestive heart failure, coronary heart disease, peptic ulcer, and gastroduodenitis. Prevalence of anemia was classified according to WHO criteria (male: hemoglobin <13 g/dL; female: <12 g/dL). To estimate the global burden of diseases, an index of comorbidity was calculated using the Charlson index (CI) score, modified by Deyo et al.13 Subjects were classified into 3 comorbidity groups as follows: CI=0; CI=1 to 2; CI>2. Onset of adverse drug reactions related to antiplatelet or anticoagulant medications prescribed during hospitalization were assessed using the Naranjo algorithm.14
Ascertainment of Drug Prescription
All drugs prescribed during hospital stay and at discharge were abstracted from hospital charts and codified according to the anatomical therapeutic chemical classification. Drugs considered for the analysis were the following antiplatelet drugs: acetyl salicylic acid, ticlopidine, indobufen, clopidogrel, dipyridamole, and picotamide; the following anticoagulant drugs were also considered: warfarin and acenocoumarol.
Cognitive and Functional Status
Cognitive and functional status was assessed at the time of admission and at discharge. Cognitive function was assessed using the Hodkinson Mental Test, a 10-item screening test for dementia.15 The presence of cognitive impairment was identified by the presence of
4 errors on the test administered at discharge.
Functional status was evaluated using 6 basic activities of daily living, including transferring from bed to chair, walking in a small room, eating, bathing, using the toilet, and personal hygiene procedures. Patients were considered with severe disability if they needed intensive assistance in at least one activities of daily living and were considered with mildmoderate disability if they needed only supervision or limited assistance in at least one activities of daily living at the time of discharge from the hospital.
Statistical Analysis
Descriptive statistic of selected characteristics was presented according to main diagnosis. We used the ANOVA to compare continuous variables and the
2 test for the comparison of proportions. Factors potentially related to antithrombotic prescription at discharge were compared in patients who had or did not have the prescription, using univariate logistic regression. Because <5% of the subject were using oral anticoagulant therapy, the analysis was performed for antiplatelet and anticoagulant drugs in combination. Multivariate logistic regression analysis was then used to identify factors independently associated with the prescription of antiplatelet or anticoagulant drugs. The selection of the variables to be included in the model was made on the basis of clinical plausibility and according to the result of the unadjusted analysis. The OR with 95% CI was used as measure of the association between demographic and clinical characteristics and the probability of being treated with antithrombotic medication.
| Results |
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At the univariate analysis (Table 2), presence of hypertension increased the likelihood of having anticoagulant or antiplatelet prescription (OR: 1.77; CI: 1.35 to 2.31). Patients with
3 stroke risk factors and patients using
2 medications were also more likely to have antithrombotic prescription. Conversely, factors inversely associated with prescription were anemia (OR: 0.65; CI: 0.49 to 0.87), severe disability (OR: 0.26; CI: 0.19 to 0.36), cognitive impairment (OR: 0.27; CI: 0.20 to 0.36), and adverse drug reaction or patient refusal during hospitalization (OR: 0.41; CI: 0.10 to 1.72).
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Multivariate logistic regression analysis (Table 3) showed that cognitive impairment (OR: 0.58; CI: 0.43 to 0.78) and severe disability (OR: 0.48; CI: 0.31 to 0.76) were inversely associated with the likelihood of treatment prescription. Other conditions significantly associated with the probability of being treated with antithrombotic therapy were diagnosis of TIA, diagnosis of anemia, and adverse drug reactions. Patients with
3 risk factors for stroke were also more likely to have the prescription, but the association was non-statistically significant (P=0.106).
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Finally, to further explore the relationship of cognitive and functional status and the treatment prescription, we performed a stratified analysis according to physical and cognitive status. This was performed creating 9 mutually exclusive groups according to cognitive and functional performance levels (Figure 2). Patients with dementia or with very low (
2) Hodkinson Mental Test scores were excluded. After adjustment for age and sex, we found an independent and additive effect of physical and cognitive status on antithrombotic therapy prescription, with patients with both good cognitive and physical function having the highest probability of being treated. Of note, even among subjects with normal cognitive function there was a graded and strong relationship between the level of physical impairment and the likelihood of antithrombotic prescription.
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| Discussion |
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Previous studies suggested that there is discrepancy between knowledge derived from clinical trial and clinical practice,17 showing that a significant number of patients with previous stroke do not receive adequate medical intervention.18 Two recent studies reported a low rate of antithrombotic treatment, but they were unable to determine whether the observed low rates were the result of hospitals failure to prescribe preventive treatment or discontinuation of the treatment by family physicians.19,20 Our results are in agreement with these observations and suggest that physicians operating in the acute care setting may, at least partially, be responsible for the low rate of antithrombotic treatment reported in several surveys. The rate of patients without antithrombotic treatment observed in our study was higher (41%) than that reported in the other studies (25% to 28%).19,20 This could be caused by the specific setting of the study, because our patients were recruited from geriatrics and internal medicine departments, and only a few were from neurology departments. Neurologists may be more prone to prescription of antithrombotic therapy for stroke prevention. Moreover, most of the important trials supporting the efficacy of secondary prevention were performed in the late 1980s and early 1990s. This time lag may have been insufficient to translate by 1993 these results into routine clinical practice. In fact, we observed a significant increment in the prescription rate between 1993 and 1997; in 1998, the rate of prescription of our study (69%) was very similar to the rate reported by another Italian study in the same year (72%).20 Indeed, more recent studies published in the past 3 years reported a higher prevalence (>70%) of patients treated with antithrombotic medications for secondary prevention of stroke;21,22 nevertheless, in agreement with our data, implementation of international guidelines seems to be not yet adequate, particularly among the oldest patients.23
The most important independent correlates of no treatment with antithrombotic therapy were cognitive impairment and disability, and the association between disability and cognitive impairment increases further the probability of being untreated. Furthermore, even among patients with normal cognitive function there was a direct and graded association between physical performance status and the likelihood of being treated. The association between disability and antithrombotic prescription rate is difficult to explain, because there is no evidence of a lower effectiveness of antithrombotic therapy in patients with functional impairment. Conversely, stroke recurrence in these patients can increase the severity of disability and worsening their quality of life.
With regard to cognitive status, some studies showed that increasing level of cognitive impairment has been associated with a decreased use of cardiovascular and analgesic medications.24 Our results seem to confirm these previous findings also in patients with stroke. Although, prescription of anticoagulant cannot be feasible in patients with severe cognitive impairment, our stratified analysis demonstrated that almost 40% of non-disabled patients with moderate cognitive impairment were not treated with any antithrombotic medication, and this rate was substantially higher compared with patients with normal cognitive function. From this point of view, it seems unlikely that the low rate of antithrombotic prescription in patients with cognitive decline would be explained by the impossibility to prescribe anticoagulants. Impaired cognitive function is associated with an increased incidence and recurrence of stroke.25 However, stroke, particularly recurrent stroke, is a strong risk factor for cognitive impairment and dementia.26
Some of the limitations of our survey have been already mentioned. Another limitation could be that patients who had ischemic stroke with secondary hemorrhagic complications were not identified; however, the prevalence of this condition is usually low and the results should not be affected by this misclassification. We considered peptic disease, gastroduodenitis, and adverse drug reaction onset during the hospital stay or patient refusal as potential contraindications for antithrombotic therapy, but the study protocol did not gather information on previous intolerance to antithrombotics. Finally, although we analyzed a number of demographic and clinical characteristics, other measures that were not available for this study, including level of disease severity, could have provided more precise and appropriate information.
In conclusion, although antithrombotic therapy has been consistently demonstrated as an effective tool in stroke secondary prevention, our results highlighted an unexpected low rate of antiplatelet and anticoagulant prescription. Our data suggest that secondary prevention of cerebrovascular disease should be substantially improved and underline the need for therapeutic decisions to be based on the best evidence and should be incorporated into routine clinical practice, particularly in older patients with moderate cognitive or functional impairment.
| Acknowledgments |
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Received October 20, 2003; revision received January 7, 2004; accepted January 8, 2004.
| References |
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