Diazepam to improve acute stroke outcome: results of the early GABA-Ergic activation study in stroke trial. a randomized double-blind placebo-controlled trial

BACKGROUND: We tested whether diazepam, a GABA-ergic drug that also inhibits brain nitric monoxide formation, improves acute stroke prognosis. METHODS: 880 patients, randomized within 12 h of acute stroke, received diazepam 10 mg or placebo by rectiole, as soon as possible, followed by 10-mg tablets twice daily for 3 days. Primary outcome was independence (Rankin score <3) at 3 months; secondary outcome was complete recovery (Barthel index >or=95 or Rankin score 相似文献   

Effect of perindopril on cerebral and renal perfusion on normotensives in mild early ischaemic stroke: a randomized controlled trial

BACKGROUND AND PURPOSE: Blood pressure reduction is central to secondary prevention after stroke, but the optimal time to start therapy is unknown. Cerebral autoregulation is impaired early after ischaemic insult, and any changes in systemic blood pressure may be reflected in cerebral perfusion. However, early initiation in hospital may better assure continued long-term treatment. We have investigated the effect of the angiotensin-converting enzyme inhibitor perindopril on blood pressure, global and focal cerebral blood flow (CBF) and glomerular filtration rate (GFR) in a normotensive acute stroke population. METHODS: Twenty-five patients within 4-8 days of mild ischaemic stroke/transient ischaemic attack and with diastolic blood pressure 70-90 mm Hg were randomized to receive perindopril 2 or 4 mg daily versus placebo according to estimated GFR. Mean arterial blood pressure (MABP), internal carotid artery (ICA) flow and middle cerebral artery velocity (MCAv) were measured prior to dosing, over the following 24 h and at 2 weeks. Brain hexamethyl propylene amino oxide single photon emission computed tomography (SPECT) was performed before dosing and at estimated time of peak drug effect (6-8 h after first dose). GFR measurement using a (51)Cr-ethylene diamine tetraacetic acid technique was undertaken prior to medication and repeated at 2 weeks. RESULTS: MABP was reduced throughout the first 24 h with a mean MABP reduction of 9.3 mm Hg (95% CI 7.4-11.3 mm Hg), maximal placebo corrected fall of 12.5 mm Hg at 10 h post-dose, p = 0.005. No significant change occurred in ICA flow, MCAv or CBF measured by SPECT: change from baseline in symptomatic hemisphere CBF was -0.02 (SD 3.11) ml/100 g/min (treated group) compared with 0 (SD 3.01) (placebo group). Similarly, no significant change was observed in cortical CBF. Mean within-group change in GFR was 2.7 +/- 10.1 in the treated group and -4.3 +/- 6.7 in the placebo group (p = NS). DISCUSSION: Antihypertensive therapy with perindopril may be introduced in the first week after mild ischaemic stroke in normotensive patients without affecting global or regional CBF or affecting GFR.     

Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder

CONTEXT: Paroxetine controlled release (CR) is approved for the treatment of major depressive disorder (MDD) in the dosage range of 25 to 62.5 mg daily. However, lower daily doses (12.5 mg and 25 mg) of this formulation have not been investigated in the treatment of MDD. If the 12.5-mg and 25-mg doses are found to be efficacious, these lower doses may well convey a superior tolerability profile for paroxetine CR in the treatment of MDD. OBJECTIVE: To evaluate the antidepressant efficacy and tolerability profile of daily doses of paroxetine CR 12.5 mg and 25 mg versus placebo in the treatment of MDD. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted in 40 clinical investigation centers in the United States. PARTICIPANTS: 447 adult (> or = 18 years of age) outpatients who met DSM-IV criteria for MDD and with a baseline 17-item Hamilton Rating Scale for Depression (HAM-D) score of at least 20 comprised the intent-to-treat study population (mean age = 38.8 years; 58.4% female; 75.6% white). INTERVENTION: Eligible patients completing a 1-week single-blind placebo run-in period were randomly assigned to receive once-a-day study medication (paroxetine CR 12.5 mg [N = 156], paroxetine CR 25 mg [N = 154], or placebo [N = 149]) in an 8-week, double-blind, parallel cell comparison. MAIN OUTCOME MEASURES: The primary efficacy measure was the change from baseline to study endpoint (week 8) as measured by the HAM-D. Secondary efficacy measures included change from baseline to study endpoint as assessed by both the depressed mood item on the HAM-D and the Clinical Global Impressions (CGI) Severity of Illness scale (CGI-S). The proportion of patients considered at study endpoint to be in response (CGI-Improvement score of 1 or 2) or in remission (HAM-D < or = 7) in the 3 treatment groups was also compared. Quality of life was assessed by the change from baseline in total score of the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Safety observations were made by assessing the proportion of patients who had adverse experiences, including laboratory and electrocardiographic abnormalities, during the treatment period. RESULTS: The primary efficacy analysis revealed that both the 12.5-mg and the 25-mg paroxetine CR treatment groups were associated with significant therapeutic effects (change in HAM-D score) from baseline to study endpoint (LOCF: p = .038, 95% CI = -3.38 to -0.09 and p = .005, 95% CI = -4.06 to -0.74, respectively). Results from the Wilcoxon rank sum test of the depressed mood item of the HAM-D (p = .011, 95% CI = -0.57 to -0.07) demonstrated significant efficacy in the 25-mg treatment group but not in the 12.5-mg group. However, LOCF analysis of the CGI-S revealed significant therapeutic effects for both the 12.5-mg (p = .018, 95% CI = -0.61 to -0.06) and 25-mg (p < .001, 95% CI = -0.78 to -0.22) treatment groups. Significantly more patients in the 25-mg paroxetine CR-treated group than in the placebo-treated group met criteria for response (CGI-Improvement score of 1 or 2, p = .035, OR = 1.68, 95% CI = 1.04 to 2.73) as well as for remission (HAM-D score 相似文献   

Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial

BACKGROUND: There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial. METHODS: Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096. FINDINGS: Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days. INTERPRETATION: Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH. FUNDING: National Health and Medical Research Council of Australia.     

Long-term outcome as function of blood pressure in acute ischemic stroke and effects of thrombolysis

BACKGROUND: While baseline blood pressure (BP) is a known predictor of 90-day residual deficit after acute ischemic stroke, the effect of thrombolysis on this relationship has not been described. To study the interaction and to find intervals of prognostic significance, the functional forms of this predictive relationship should be found and compared for recombinant tissue plasminogen activator (rt-PA)- and placebo-treated patients of the first European Cooperative Acute Stroke Study. METHODS: We studied the 615 patients with acute ischemic hemispheric stroke randomized and treated in the first European Cooperative Acute Stroke Study. Endpoints were fatal outcome within and favorable outcome (no or negligible long-term handicap on the modified Rankin Scale scores 0 or 1) after 90 +/- 14 days. Functional relationships with baseline BP were estimated fully nonparametrically as moving averages of occurrences of either outcome among placebo- and rt-PA-treated patients, separately. Visual findings were corroborated by conventionally stratified logistic regression. RESULTS: For favorable outcome, an S-shaped functional relationship with baseline systolic BP (SBP) was found with an averaged incremental rate around 10% per 1 mm Hg increase in baseline SBP between 140 and 160 mm Hg, among rt-PA and placebo patients. Similar results were obtained for diastolic BP (DBP) between 80 and 90 mm Hg. Odds ratios in favor of rt-PA were 1.96 (95% CI: 1.02-3.78) and 2.87 (95% CI: 1.36-6.04) for SBP and DBP in these intervals, respectively. For mortality, visible markedly lower risks in the placebo group between 120 and 140 and between 160 and 180 mm Hg SBP were confirmed with adjusted OR of 2.47 (95% CI: 1.09-5.64) and 9.73 (95% CI: 2.02-46.82), respectively. CONCLUSIONS: Patients benefited from rt-PA in terms of no or negligible handicap after 90 days, without excess risk of death, with baseline SBP between 140 and 160 mm Hg or baseline DBP between 80 and 90 mm Hg.     

Characteristics of in-hospital onset ischemic stroke

BACKGROUND AND PURPOSE: The aim of the present study was to clarify the clinical characteristics of in-hospital onset stroke. MATERIAL AND METHODS: We analyzed 15,815 patients with acute brain infarction registered in the Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC) registry. RESULTS: The in-hospital onset group included 694 (4.4%) patients and the out-of-hospital group included 15,121 (95.6%) patients. Atrial fibrillation (AF) was more common in the in-hospital onset group (34.6%) than in the out-of-hospital group (20.4%, p < 0.001). The admission NIHSS score (median, in-hospital 13 vs. out-of-hospital 5, p < 0.0001) and the mortality rate at discharge were higher in the in-hospital group than in the out-of-hospital group (in-hospital 19.2% vs. out-of-hospital 6.8%, p < 0.0001). On multivariate logistic regression analyses, female gender (OR 1.1, 95% CI 1.1-1.3), older age (OR 1.0, 95% CI 1.02-1.03), AF (OR 4.4, 95% CI 4.0-4.8), history of stroke (OR 1.3, 95% CI 1.2-1.4) and in-hospital stroke onset (OR 3.3, 95 %CI 2.7-3.9) were independent factors associated with severe stroke (NIHSS score > or =11), and older age (OR 1.03, 95% CI 1.02-1.04), the presence of AF (OR 1.21, 95% CI 1.0-1.5), in-hospital stroke onset (OR 1.01, 95% CI 1.01-1.02) and NIHSS score at initial evaluation (OR 1.15, 95% CI 1.14-1.17) were independent factors associated with death at discharge. Conclusion: In-hospital stroke onset was not uncommon. The neurological deficits in patients with in-hospital onset stroke were severer and the outcome was worse than in those with out-of-hospital stroke. Therefore, a strategy to reduce in-hospital stroke onset should be implemented.     

Ginsenoside-Rd improves outcome of acute ischaemic stroke - a randomized, double-blind, placebo-controlled, multicenter trial

Background and purpose: Ginsenoside‐Rd is a receptor‐operated calcium channel antagonist and has shown promise as a neuroprotectant in our phase II study. As an extended work, we sought to confirm its efficacy and safety of Ginsenoside‐Rd in patients with acute ischaemic stroke. Methods: We conducted a randomized, double‐blind, placebo‐controlled trial involving 390 patients with acute ischaemic stroke in a 3:1 ratio to receive a 14‐day intravenous infusion of Ginsenoside‐Rd or placebo within 72 h after the onset of stroke. Our primary end‐point was the distribution of disability scores on the modified Rankin scale (mRs) at 90 days. Results: The efficacy analysis was based on 386 patients (Ginsenoside‐Rd group: 290; placebo group: 96). Ginsenoside‐Rd significantly improved the overall distribution of scores on the mRs, as compared with the placebo (P = 0.02; odds ratios [OR], 1.74; 95% confidence interval [CI], 1.08–2.78). There were significant differences between the two groups when we categorized the scores into 0–1 vs. 2–5 (P = 0.01; OR, 2.32; 95% CI, 1.23–4.38; 66.8% vs. 53.1%). It also improved the National Institutes of Health Stroke Scale (NIHSS) at 15 days [P < 0.01; least squares mean (LSM), ?0.77; 95% CI, ?1.31 to ?0.24]. Mortality and rates of adverse events were similar in the two groups. Conclusions: Ginsenoside‐Rd improved the primary outcome of acute ischaemic stroke and had an acceptable adverse‐event profile.     

Trends in five-year survival and risk of recurrent stroke after first-ever stroke in the Perth Community Stroke Study

BACKGROUND: Few studies provide information on trends in the long-term outcome of stroke. We aimed to determine trends in survival and recurrent stroke, over 5 years after first-ever stroke, for 2 cohorts of patients enrolled in the Perth Community Stroke Study in 1989-90 and 1995-96. METHODS: For 12-month periods beginning February 1989 and February 1995, all individuals with an acute stroke who were resident in a geographically-defined and representative region of Perth, Western Australia, were registered and followed-up prospectively 5 years after the index event. RESULTS: The 5-year cumulative risk of death was 59% (95% confidence interval (CI) 53%, 65%) and 58% (95% CI 52%, 65%) for the 1989-90 and 1995-96 cohorts, respectively (p = 0.94). The 5-year cumulative risk of first recurrent stroke was 32% (95% CI 25%, 40%) and 23% (95% CI 16%, 30%) for the 1989-90 and 1995-96 cohorts, respectively (p = 0.07). CONCLUSIONS: Although no statistically significant improvement occurred in 5-year survival after first-ever stroke in Perth between 1989-90 and 1995-96, there was a statistically nonsignificant trend towards a smaller cumulative risk of recurrent stroke over 5 years after a first-ever stroke. Serial community-based studies of the incidence and outcome of stroke are an important means of monitoring the translation of proven preventive interventions to improvements in population health.     

Prophylaxis of deep venous thrombosis and adherence to guideline recommendations among inpatients with acute stroke: results from a multicenter observational longitudinal study in China

INTRODUCTION: Deep venous thrombosis (DVT) is a common complication in acute stroke. Evidence-based guidelines recommend the use of prophylactic heparins in patients with risk of DVT. We aimed to evaluate the clinical practices for DVT prophylaxis in acute stroke inpatients enrolled in a multicenter observational longitudinal study on deep venous thrombosis (Incidence of Deep Venous Thrombosis after Acute Stroke in China, INVENT-China). MATERIALS AND METHODS: Patients' characteristics and DVT prophylaxis was extracted from the database of INVENT-China. Appropriate adherence to the guidelines was analysed. RESULTS: Six hundred and fifty-six patients with acute stroke were eligible for analysis in this study. Pharmacologic prophylaxis with low-molecular-weight heparins (LMWH) was applied to 18 patients with ischemic stroke (3.4%) and one patient with cerebral hemorrhage. Independent factors associated with use of prophylactic anticoagulant treatment were stroke subtype (OR=0.07, 95% CI=0.01-0.78, p=0.03), baseline NIHSS score (OR=0.25, 95% CI=0.07-0.95, p=0.04), baseline motor leg function (NIHSS score) (score=1, OR=0.16, 95% CI=0.03-0.79, p=0.025; score=2, OR=0.20, 95% CI=0.05-0.84, p=0.028; score=3, OR=0.23, 95% CI=0.06-0.91, p=0.037; score=4, reference), diabetes mellitus (OR=3.86, 95% CI=1.39-10.72, p=0.009), malignancy (OR=9.55, 95% CI=1.98-46.2, p=0.005), varicose veins (OR=12.48, 95% CI=1.64-94.9, p=0.015) and central venous catheterization (OR=6.96, 95% CI=1.36-35.79, p=0.02). CONCLUSION: Thromboprophylaxis is inadequate in acute stroke inpatients in China. Guidelines for prevention DVT in acute stroke should be established and efforts should be made to improve venous thromboembolism prophylaxis practice.     

Genetic predisposition to stroke in relatives of hypertensives

BACKGROUND AND PURPOSE: The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to test the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors. METHODS: Genealogical and medical history information was obtained for a cohort of 354 hypertensive probands ascertained in a clinic-based setting, their 1427 first-degree relatives, and 239 of their spouses. Risks of stroke and hypertension in biological and nonbiological relatives were compared with the logistic model of the generalized estimating equations adjusted for age and sex. RESULTS: The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio [OR]=2.4; 95% CI, 1.8 to 3.4; OR=2.2; 95% CI, 1.6 to 3.0, respectively). When the spouses were used as a reference group, the risk of stroke for parents of the hypertensive probands was 7.3 times higher (OR=7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings (OR=1.6; 95% CI, 0.8 to 3.3) was observed. Controlling for hypertension, obesity, smoking, coronary heart disease, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (OR(parents)=5.4; 95% CI, 2.6 to 11.2; OR(siblings)=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher for hypertensive parents and siblings than for nonhypertensive parents (OR=5.2; 95% CI, 2.8 to 9. 7) and siblings (OR=5.8; 95% CI, 2.1 to 15.9). A history of hypertension was not associated with an increased risk for stroke in spouses (OR=0.7; 95% CI, 0.2 to 3.1). The risk of stroke in hypertensive relatives of probands with stroke was higher than that of the normotensive relatives (OR=13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (OR=4.0). CONCLUSIONS: Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that some of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not significant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treatment for hypertension. Although a history of hypertension increases the risk of stroke among parents and siblings, multivariate analyses revealed a familial component to stroke independent of hypertension.     

The time course and determinants of blood pressure within the first 48 h after ischemic stroke

BACKGROUND AND PURPOSE: Previous research suggests that blood pressure falls acutely after ischemic stroke. We aimed to further characterize this fall with a statistical technique that allows the application of regression techniques to serial blood pressure outcome data. METHODS: In a prospectively recruited ischemic stroke cohort, systolic (SBP) and diastolic (DBP) blood pressure was recorded every 4 h until 48 h after stroke. Potential determinants of blood pressure, including stroke severity and acute infection, were also recorded. Mixed effects models were used to model serial blood pressure measurements over time, adjusted for significant determinants. RESULTS: In 156 patients, SBP and DBP fell by 14.9 mm Hg (95% CI 6.2-22.6 mm Hg) and 6.2 mm Hg (95% CI 1.4-10.6 mm Hg), respectively, over the first 48 h after stroke. SBP was higher in patients with premorbid hypertension, a previous history of stroke or TIA, current alcohol use, increasing age, stroke of mild to moderate severity (NIHSS 3-13) and in patients treated with antihypertensives. SBP was lower in smokers. There was a progressive rise in SBP in patients with acute infection. No factors other than time were associated with DBP. CONCLUSIONS: The use of mixed effects models has identified a linear SBP and DBP fall over the first 48 h after stroke. The timing and magnitude of this fall should be accounted for in the design of future prognostic and intervention studies.     

Blood Pressure, smoking and oral contraceptive control after cryptogenic stroke in young adults in the PFO-ASA Study

BACKGROUND: Management of vascular risk factors is not optimal in stroke patients. We assessed the control of hypertension, smoking and stopping of oral contraceptive in 581 consecutive young cryptogenic ischemic stroke patients followed in the PFO-ASA study and we identified factors associated with inadequate management. METHODS: At each follow-up visit, blood pressure (BP), smoking and use of oral contraceptive were recorded. Data were analyzed at 6 months, 1 and 2 years. Hypertension was defined as systolic BP > or = 140 or diastolic BP > or = 90 mm Hg, recorded in at least two follow-up visits. Current smoking was defined as more than one cigarette per day reported during at least one follow-up visit. RESULTS: During follow-up, 36% of patients were hypertensive and 30% were smokers. Among the 90 hypertensive patients at baseline, 60-68% remained with high BP and among the 278 patients who were current smokers at baseline, 54-58% still smoked during follow-up. Age (OR = 1.05, 95% CI 1.02-1.08), male sex (OR = 1.42, 95% CI 0.93-2.18), body mass index > or = 27 (OR = 2, 95% CI 1.27-3.17) and known hypertension (OR = 3.08, 95% CI 1.80-5.28) were significantly associated with hypertension during follow-up. Tobacco consumption at baseline (OR = 35.2, 95% CI, 19.3-64.2), alcohol consumption at baseline (OR = 2.7, 95% CI 1.4-5.2) and Rankin < or = 2 (OR = 2.6, 95% CI 1.4-4.9) were independently associated with persistent smoking. Among the 114 women who were using combined estrogen-progesterone pills at baseline, 96.5% stopped. CONCLUSIONS: Major risk factors for stroke are poorly controlled after stroke, even in the context of a prospective clinical study in young adults.     

Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta-analysis of randomized controlled trials

BACKGROUND AND PURPOSE: Low-molecular-weight heparins and heparinoids (LMWHs) are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism and acute coronary syndromes. We performed a systematic review of randomized controlled trials (RCTs) to examine the safety and efficacy of LMWH in acute ischemic stroke. METHODS: Randomized, controlled, and nonconfounded trials of LMWH in acute ischemic stroke were identified from the Cochrane Library (version 2, 1999), previous systematic reviews, and a review of publication quality relating to acute stroke trials. The authors each independently extracted data by treatment group and assessed trial quality using Cochrane Collaboration criteria. RESULTS: Eleven completed RCTs involving 3048 patients were identified; data were available from 10 of these. Four trials explicitly excluded patients with presumed cardioembolic stroke. Treatment with LMWH was associated with significant reductions in prospectively identified deep vein thrombosis (OR 0.27, 95% CI 0.08 to 0.96) and symptomatic pulmonary embolism (OR 0.34, 95% CI 0.17 to 0.69) and with increased major extracranial hemorrhage (OR 2.17, 95% 1.10 to 4.28). Nonsignificant increases in end-of-treatment (OR 1.20, 95% CI 0.86 to 1.69) and end-of-trial (OR 1.05, 95% CI 0.83 to 1.32) case fatality and symptomatic intracranial hemorrhage (OR 1.77, 95% CI 0. 95 to 3.31) were observed. End-of-trial death and disability was nonsignificantly reduced (OR 0.87, 95% CI 0.72 to 1.06). CONCLUSIONS: ++LMWHs reduce venous thromboembolic events in patients with acute ischemic stroke and increase the risk of extracranial bleeding. A nonsignificant reduction in combined death and disability and nonsignificant increases in case fatality and symptomatic intracranial hemorrhage were also observed. On the basis of the current evidence, LMWH should not be used in the routine management of patients with ischemic stroke.     

Statins and stroke prevention

Over the past decade, statins have been proven to significantly decrease coronary events in primary and secondary prevention of coronary artery disease. Recent clinical trials have indicated that statins significantly reduce stroke risk in patients with vascular disease. The Cholesterol Treatment Trialists' Collaborators in a meta-analysis including 90,056 patients found that the use of statins determined a significant 17% proportional reduction in the incidence of first-ever stroke of any type per 1 mmol/l low-density lipoprotein (LDL) cholesterol reduction. During an average of 5 years of treatment, the reduction in the overall incidence of stroke was about one sixth per 1 mmol/l LDL cholesterol decrease meaning that 8 fewer participants have any stroke per 1,000 among those with preexisting coronary artery disease at baseline, compared with 5 fewer per 1,000 among the participants with no such history. It is not known whether these findings might be due to the cholesterol reduction effect of statins or to pleiotropic effects of statins, such as improved endothelial function, decreased platelet aggregability, and reduced vascular inflammation. In secondary prevention of stroke, the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study found that treatment with atorvastatin reduced the risk of recurrent cerebrovascular events in patients with recent stroke or transient ischemic attack but no history of heart disease. Combining the results of patients with no history of heart disease from the SPARCL study and Heart Protection Study in a mini meta-analysis, compared with placebo, statins were associated with a barely nonsignificant difference in recurrent stroke (OR = 0.87, 95% CI = 0.75-1.01, p = 0.07) and a significant difference in the occurrence of major vascular events (OR = 0.78, 95% CI = 0.68-0.88, p = 0.0001) at final follow-up.     

Evaluating the efficacy of acupuncture in defined aspects of stroke recovery

OBJECTIVE: To investigate the efficacy of acupuncture on stroke recovery compared to an inert placebo. DESIGN : Placebo-controlled, randomised, clinical trial. SETTING: Post-stroke rehabilitation wards in five NHS hospitals in the UK. SUBJECTS: Patients between 4 and 10 days after their first stroke. INTERVENTIONS AND OUTCOME MEASURES: The patients received 12 acupuncture or placebo treatments over four weeks. Acupuncture with electrical stimulation was compared with mock TENS, and assessments continued for 12 months after entry. Primary outcome was the Barthel Index (BI). Secondary outcomes were muscle power, Motricity Index (MI), mood, Nottingham Health Profile (NHP) and treatment credibility. RESULTS: 92 patients completed data sets. Data were analysed using both t tests and a structural equation based on longitudinal analysis of both BI and MI, using generalised estimating equations with an exchangeable correlation structure. While both acupuncture and placebo (mock TENS) appeared to have had an equal effect on stroke recovery, there is no significant difference between the two interventions at 12 (p = 0.737, 95 % CI -2.00 to 2.81) and 52 weeks (p = 0.371, 95 % CI -3.48 to 1.32). An apparently accelerated improvement in the MI scores in the acupuncture group at 3 weeks (p = 0.009, 95 % CI 1.55 to 10.77) is interesting. CONCLUSIONS: Acupuncture did not demonstrate specific efficacy over placebo and both groups did as well as normally expected with this condition.     

Geographic variation in stroke risk in the United States. Region, urbanization, and hypertension in the Third National Health and Nutrition Examination Survey

BACKGROUND: In the United States, stroke mortality is higher in the south than in other regions. Hypertension is the main risk factor for stroke among older adults; however, few studies have examined group-specific regional and urbanization differences in hypertension prevalence. METHODS: Data from the Third National Health and Nutritional Examination Survey (NHANES III), 1988 to 1994, were analyzed to calculate the prevalence of hypertension (systolic >140 mm Hg and/or diastolic >90 mm Hg and/or taking antihypertensive medication) by region and urbanization for age (40 to 59 and 60 to 79 years), sex, and ethnic subgroups. Logistic regression models were fitted to estimate the association of hypertension with region and urbanization. RESULTS: With age and urbanization kept constant, southern residence was associated with hypertension among middle-aged non-Hispanic white men (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.12 to 1.90; P<0.006), non-Hispanic black men (OR, 1.36; 95% CI, 1.05 to 1.66; P=0.019), and non-Hispanic black women (OR, 1.23; 95% CI, 1.01 to 1.45; P=0.034). Among older non-Hispanic white men, a significant interaction was noted between region and urbanization (P=0.01), with a higher prevalence in the south only for nonmetropolitan residents (OR, 1.32; 95% CI, 1.06 to 1.56; P<0.013). A similar but not statistically significant trend was also confirmed among non-Hispanic black men in logistic regression analysis (OR, 1.38; 95% CI, 0.97 to 1.68; P=0.061). No statistically significant association was observed for urbanization or region in the other subgroups. CONCLUSIONS: Southern residence was associated with increased hypertension prevalence among middle-aged non-Hispanic white men, non-Hispanic black men and women, and older non-Hispanic white men.     

A systematic review of the associations between age and sex and the operative risks of carotid endarterectomy

BACKGROUND: Randomized trials of carotid endarterectomy (CEA) for both symptomatic and asymptomatic carotid stenosis have demonstrated that benefit is decreased in women, due partly to a high operative risk, which is independent of age. However, it is uncertain whether these trial-based observations are generalisable to routine clinical practice. METHODS: We performed a systematic review of all publications reporting data on the association between age and/or sex and procedural risk of stroke and/or death following CEA from 1980 to 2004. RESULTS: 62 eligible papers reported relevant data. Females had a higher rate of operative stroke and death (25 studies, OR = 1.31, 95% CI = 1.17-1.47, p < 0.001) than males, but no increase in operative mortality (15 studies, OR = 1.05, 95% CI = 0.81-0.86, p = 0.78). Compared with younger patients, operative mortality was increased at > or =75 years (20 studies, OR = 1.36, 95% CI = 1.07-1.68, p = 0.02), at age > or =80 years (15 studies, OR = 1.80, 95% CI = 1.26-2.45, p < 0.001) and in older patients overall (35 studies, OR = 1.50, 95% CI = 1.26-1.78, p < 0.001). In contrast, risk of non-fatal stroke did not increase with age and so the combined perioperative risk was only slightly increased at age > or =75 years (21 studies, OR = 1.18, 95% CI = 0.94-1.44, p = 0.06), at age > or =80 years (10 studies, OR = 1.14, 95% CI = 0.92-1.36, p = 0.34) and in older patients overall (36 studies, OR = 1.17, 95% CI = 1.04-1.31, p = 0.01). CONCLUSIONS: The effects of age and sex on the operative risk of CEA in published case series are consistent with those observed in the trials. Operative risk of stroke is increased in women and operative mortality is increased in patients aged > or =75 years.     

Clinically relevant cognitive impairment after cardiac surgery: a 6-month follow-up study

BACKGROUND AND PURPOSE: The majority of studies on neuropsychological complications after cardiac surgery used the raw variation of selective tests scores to define the occurrence of cognitive decline. We prospectively estimated the frequency of cognitive impairment after cardiac surgery, with a particular emphasis on persistent and clinically relevant cognitive decline. Possible baseline and operative predictors were also evaluated. METHODS: An extensive neuropsychological battery was administered to 110 patients (mean age 64.1+/-9.4 years; 70.9% males) undergoing cardiac surgery before and 6 months after the operation. After evaluating the variations in the cognitive performances, two independent neuropsychologists ranked the patients as unchanged-improved, mildly-moderately deteriorated, or severely deteriorated, using a global and functionally oriented judgement. The degree of the impairment was determined in relation to its impact on everyday life activities. RESULTS: Ten patients (9.1%) were ranked as severely deteriorated, 22 (20%) as mildly-moderately deteriorated, and 78 (70.9%) as unchanged-improved. Cognitively impaired patients were older (p=0.031), more often females (p=0.005), with a low education level (p=0.013). At multivariate analysis, female gender (odds ratio (OR) 6.14, 95% confidence interval (95% CI) 2.16-17.50), baseline use of beta-blockers (OR 4.55, 95% CI 1.30-15.92), and PaO2 at arrival in intensive care unit (OR for 1 mm Hg increment 1.012, 95% CI 1.004-1.020) were significant predictors of cognitive impairment of any degree. Positive predictors of severe cognitive impairment were history of hypertension (OR 5.33, 95% CI 1.03-27.64) and PaO2 at arrival intensive care unit (OR for 1 mm Hg increment 1.020, 95% CI 1.006-1.035), while education was protective (OR per year of increment 0.53, 95% CI 0.31-0.90). CONCLUSIONS: A considerable proportion of cardiac surgery patients may undergo clinically relevant cognitive impairment. The knowledge of variables influencing cognitive outcome is essential for the adoption of preventive measures.     

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke

BACKGROUND: The administration of tissue plasminogen activator (t-PA) has been proven effective for ischemic stroke within 3 h after onset. A pooled-analysis of six trials showed that intravenous t-PA still improves outcome when given between 3 to 4.5 h after stroke onset. On the basis of this pooled analysis, t-PA was also routinely offered to our patients between 3-4.5 h. We report the safety and clinical features of this group together with the features of the group given t-PA within 3 h. METHODS: Prospectively patient characteristics, stroke severity, stroke subtype, incidence of symptomatic intracerebral hemorrhage (SICH), in-hospital mortality, and 3-months modified Rankin Scale scores (mRS) were registered. Data was analyzed separately for patients treated within 3 h (early group) and those treated between 3-4.5 h (late group). RESULTS: Among 176 patients who underwent intravenous thrombolysis, 101 were treated in the early group and 75 in the late group. Six (5.9%; 95% CI 2.8%-12.3%) patients in the early group and 4 (5.3%; 95% CI 2.2%-12.9%) in the late group developed SICH (p=1.0). In the early group 13 (12.9%; 95% CI 7.7%-20.8%) patients died within 7 days after admission, compared to 5 (6.7%; 95% CI 3.0%-14.7%) in the late group (p=0.179). In the early group 44 (43.6%; 95% CI 43.3%-53.3%) were independent (mRS< or =2) at three months, compared to 36 (48.0%; 95% CI 37.0%-59.1%) in the late group (p=0.559). CONCLUSION: Our data show no trend of decreased safety of thrombolysis beyond 3 h. Due to a small sample size a harmful effect cannot be excluded but seems unlikely.