OBJECTIVES: To assess how much of the excess risk of poor outcome from stroke in people aged 80 and older aging per se explains, independent of other prognostic determinants.
DESIGN: Cohort, ...observational.
SETTING: University hospital.
PARTICIPANTS: One thousand five hundred fifty‐five patients with first‐ever ischemic stroke consecutively referred to an in‐hospital Clinical Pathway program were studied.
MEASUREMENTS: The relationship between age and 1‐month outcome (death, disability (modified Rankin Scale 3–5), and poor outcome (modified Rankin Scale 3–6)) was assessed, with adjustment for several prognostic factors.
RESULTS: Six hundred twelve patients aged 80 and older showed worse outcome after 1 month than those who were younger, in terms of mortality (19% vs 5%, hazard ratio (HR)=3.85, 95% confidence interval (CI)=2.8–5.4) and disability (51% vs 33%, odds ratio (OR)=3.16, 95% CI=2.5–4.0), although in multivariate models, the adjusted HR for mortality decreased to 1.47 (95% CI=1.0–2.16) and the ORs for disability and poor outcome decreased to 1.76 (95% CI=1.32–2.3.) and 1.83 (95% CI=137–2.43), respectively. Stroke severity, the occurrence of at least one medical complication, and premorbid disability explained most of the risk excess in the oldest‐old.
CONCLUSION: Stroke outcome is definitely worse in very old people, and most of the excess risk of death and disability is attributable to the higher occurrences of the most‐severe clinical stroke syndromes and of medical complications in the acute phase. These represent potential targets for preventive and therapeutical strategies specifically for elderly people.
Systematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. ...We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness.
Campaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced.
In phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2 hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential "patients" and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2 hours had been advised by a family member to call EMS. To act on people's tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination.
The IM approach allowed to develop a stroke campaign integrating theories, scientific evidence and information collected from the target population, and enabled to provide clear explanations for the reasons behind key decisions during the intervention development process.
NCT01881152 . Retrospectively registered June 7 2013.
The modified Charlson Comorbidity Index (MCCI) has been proposed as a tool for adjusting the outcomes of stroke for comorbidity, but its validity in such a context has been evaluated in only a few ...studies and needs to be further explored, especially in elderly patients. We aimed to retrospectively assess the validity of the MCCI as a predictor of the short-term outcomes in a cohort of 297 patients with first-ever ischemic stroke, older than 60 years, and managed according to a clinical pathway. The poor outcome (PO) at 1 month, defined as a modified Rankin Scale score of 3-6, was the primary end point. Furthermore, a new comorbidity index has been developed, specific to our cohort, according to the same statistical approach used for the original CCI. The MCCI showed a positive association with PO (odds ratio OR 1.62; 95% confidence interval CI .98-2.68) and mortality (hazard ratio HR 1.85; 95% CI .94-3.61), not statistically significant and totally dependent on its association with the severity of neurologic impairment at onset. The new comorbidity index showed, as expected, a significant association with the PO and mortality with higher point estimates of OR (2.74; 95% CI 1.64-4.59) and HR (2.73; 95% CI 1.51-4.94), but this association was also dependent on stroke severity and premorbid disability. Our results do not support the validity of the MCCI as a predictor of the short-term outcomes in elderly stroke patients nor could we develop a more valid index from the available data. This suggests the need for development of disease- and age-specific indexes, possibly according to a prospective design. In any case, initial stroke severity, a strong predictor of outcome, is associated with the degree of comorbidity.
To examine whether serum insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) concentrations, determined early after the onset of stroke, are predictive of clinical outcome in ...elderly patients.
The sample comprised 85 patients (mean ± SD age, 83 ± 7.4 years; range, 67 to 99 years; 34% male) who were admitted with acute stroke to a geriatric ward between January 1998 and June 2000, and 88 control patients who were similar in age and sex. Clinical and laboratory assessments, computed tomographic scan of the head, carotid ultrasonography, and electrocardiography were employed to define the clinical and etiologic stroke subtype. Fasting blood samples were collected within 24 hours of admission for IGF-I and IGFBP-3 measurement. Univariate and multiple logistic regression analyses, with adjustment for other related clinical covariates, were used to assess the relation of IGF-I and IGFBP-3 to poor outcome, defined as severe disability (Barthel index <60/100) or death, at 1 month (or at discharge), 3 months, and 6 months.
Mean (± SD) IGF-1 levels were lower in patients with stroke than in controls (69 ± 45 ng/mL vs. 102 ± 67 ng/mL,
P adjusted for age = 0.001). The mean IGF-1/IGFBP-3 molar ratio was also lower in stroke patients (0.12 ± 0.07 vs. 0.19 ± 0.09,
P adjusted for age <0.0001). However, there was no relation of hormone levels to either the clinical subtype of stroke or the extent of neurologic impairment. IGF-1 levels were inversely related to poor outcome (mainly death) at 3 and 6 months, independent of other clinical covariates that were highly predictive of outcome, such as age and stroke scale score on admission (hazard ratio for death at 6 months for each 20-ng/mL increase = 0.7; 95% confidence interval: 0.5 to 0.9). An independent association of the molar ratio with death at 3 and 6 months was also found.
Low levels of circulating IGF-1 may predict the clinical outcome of stroke in elderly patients.
Background Pre-hospital delay in acute stroke is critical to the administration of thrombolysis and affects patients' clinical outcome. In this study, the impact of pre-hospital delay on the outcome ...of ischemic stroke was investigated in an Italian cohort of patients who did not receive thrombolysis. Methods Data from a cohort of 1847 patients, suffering from first-ever ischemic stroke and referred to an in-hospital clinical pathway were analyzed retrospectively. The relationship between pre-hospital delay and 1-month mortality was assessed with adjustment for demographics, premorbid disability, and stroke severity, which was graded according to the Scandinavian Stroke Scale, with higher scores indicating less severity. Results Five hundred and twelve patients (27.7%) arrived at hospital within 2 hours of symptom onset. A significant correlation was found between early arrival and a reduced risk of 1-month mortality (hazard ratio .65; 95% confidence interval .48-.89; P = .02). There was a significant interaction ( P = .01) between pre-hospital delay and the neurological score on mortality in the multivariate model, and the survival advantage of early admission was significant only for patients with scores on the Scandinavian Stroke Scale less than 18 (hazard ratio .54; 95% confidence interval .34-.85; P = .008). Conclusions Our study suggests that reducing pre-hospital delay can increase the probability of survival in patients with ischemic stroke, especially those who are most severely affected. Even if the patients cannot benefit from thrombolysis, survival rates can be increased provided that they are managed according to standardized care processes.
BACKGROUND AND PURPOSE—The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial ...fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke.
METHODS—The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke.
RESULTS—Of the 1029 patients enrolled, 123 had 128 events (12.6%)77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 dayshazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003).
CONCLUSIONS—Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.
In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major ...bleedings remain uncertain.
This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment.
After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA
DS
-VASc score after the index event (odds ratio OR, 1.2 95% CI, 1.0-1.3 for each point increase;
=0.05) and hypertension (OR, 2.3 95% CI, 1.0-5.1;
=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 95% CI, 1.0-1.2 for each year increase;
=0.002), history of major bleeding (OR, 6.9 95% CI, 3.4-14.2;
=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 95% CI, 1.4-5.5;
=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 95% CI, 0.8-1.7).
Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.
The "1-3-6-12-day rule" for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings ...that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity.
The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0-7), moderate (8-15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation.
In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)-initiating DOACS within 1, 2, 3, and 4 days, respectively-than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 95% CI, 0.27-0.89), as was ischemic stroke (1.7% versus 3.2%, 0.54 0.27-0.999). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data.
In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.
BACKGROUND AND PURPOSE—Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control ...study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention.
METHODS—Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment.
RESULTS—Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio OR, 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61).
CONCLUSIONS—In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.