Secondary preventive medication persistence and adherence 1 year after stroke.

OBJECTIVE: Data on long-term use of secondary prevention medications following stroke are limited. The Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) Registry assessed patient, provider, and system-level factors influencing continuation of prevention medications for 1 year following stroke hospitalization discharge. METHODS: Patients with ischemic stroke or TIA discharged from 106 hospitals participating in the American Heart Association Get With The Guidelines-Stroke program were surveyed to determine their use of warfarin, antiplatelet, antihypertensive, lipid-lowering, and diabetes medications from discharge to 12 months. Reasons for stopping medications were ascertained. Persistence was defined as continuation of all secondary preventive medications prescribed at hospital discharge, and adherence as continuation of prescribed medications except those stopped according to health care provider instructions. RESULTS: Of the 2,880 patients enrolled in AVAIL, 88.4% (2,457 patients) completed 1-year interviews. Of these, 65.9% were regimen persistent and 86.6% were regimen adherent. Independent predictors of 1-year medication persistence included fewer medications prescribed at discharge, having an adequate income, having an appointment with a primary care provider, and greater understanding of why medications were prescribed and their side effects. Independent predictors of adherence were similar to those for persistence. CONCLUSIONS: Although up to one-third of stroke patients discontinued one or more secondary prevention medications within 1 year of hospital discharge, self-discontinuation of these medications is uncommon. Several potentially modifiable patient, provider, and system-level factors associated with persistence and adherence may be targets for future interventions.

Worse blood pressure control in patients with cerebrovascular or peripheral arterial disease compared with coronary artery disease.

OBJECTIVES: Poor blood pressure (BP) control is common amongst patients with symptomatic atherothrombotic disease. It is unclear whether BP control and management differ across atherothrombotic disease subtypes. METHODS: We analysed the baseline data of 44,984 patients with documented coronary artery disease (CAD) only (n = 30,414), cerebrovascular disease (CVD) only (n = 11,359) and peripheral arterial disease (PAD) only (n = 3211) from the international REduction of Atherothrombosis for Continued Health Registry and investigated the impact of atherothrombotic disease subtype on BP control and use of antihypertensive drugs. RESULTS: The proportion of patients with BP controlled (<140/90 mmHg) was higher in CAD (58.1%) than in CVD (44.8%) or PAD (38.9%) patients (P < 0.001). Amongst patients with treated hypertension, CAD patients were more likely to have BP controlled than were CVD patients [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.59-1.75] or PAD (OR = 2.30; 95% CI = 2.10-2.52). These differences were smaller in women than in men and decreased with age. Amongst treated patients, CAD patients were more likely to receive > or =3-drug combination therapies than were CVD (OR = 1.73; 95% CI = 1.64-1.83) or PAD (OR = 1.64; 95% CI = 1.49-1.80) patients. Adjustment for age, gender, waist obesity, diabetes, education level and world region did not alter the results. CONCLUSIONS: Coronary artery disease patients are more likely than CVD or PAD patients to have BP controlled and to receive antihypertensive drugs, particularly combination therapies. Promotion of more effective BP control through combination antihypertensive therapies could improve secondary prevention and therefore prevent complications in CVD and PAD patients.

High cardiovascular event rates in patients with asymptomatic carotid stenosis: the REACH Registry.

BACKGROUND AND PURPOSE: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS > or =70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. METHODS: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either > or =3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. RESULTS: Compared with patients without ACAS (n = 30 329), patients with ACAS (n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82-5.65, P < 0.0001). CONCLUSION: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events.

Current strategies for ischemic stroke prevention: role of multimodal combination therapies.

Stroke remains a global leading cause of death and long-term disability, highlighting the need for more effective treatment approaches. The majority of strokes are of ischemic origin, often caused by large- or small-artery atherothrombosis, or cardioembolism. Considering the systemic nature of the atherothrombotic disease process, stroke patients are at increased risk for ischemic events in several vascular territories: cerebral, coronary and peripheral. Due to the limited options for acute stroke therapies, stroke prevention is an important therapeutic approach. In addition to the management of modifiable risk factors such as hypertension, dyslipidemia and smoking through pharmacotherapy or lifestyle adjustments, anticoagulants, surgical and perhaps endovascular approaches are indicated in certain patients. Antiplatelet therapies using various agents are a cornerstone of secondary stroke prevention. To ensure the appropriate continuum of care after hospitalization for ischemic stroke, some interventions for the prevention of recurrent ischemic stroke should be initiated during the acute hospitalization setting and maintained in the out-patient setting.

Acute physiological derangement is associated with early radiographic cerebral infarction after subarachnoid haemorrhage.

BACKGROUND: Cerebral infarction after aneurysmal subarachnoid haemorrhage (SAH) is presumed to be due to cerebral vasospasm, defined as arterial lumen narrowing from days 3 to 14. METHODS: We reviewed the computed tomography scans of 103 patients with aneurysmal SAH for radiographic cerebral infarction and controlled for other predictors of outcome. A blinded neuroradiologist reviewed the angiograms. Cerebral infarction from vasospasm was judged to be unlikely if it was visible on computed tomography within 2 calendar days of SAH or if angiography showed no vasospasm in a referable vessel, or both. RESULTS: Cerebral infarction occurred in 29 (28%) of 103 patients with SAH. 18 patients had cerebral infarction that was unlikely to be due to vasospasm because it was visible on computed tomography by day 2 (6 (33%)) or because angiography showed no vasospasm in a referable artery (7 (39%)), or both (5 (28%)). In a multivariate model, cerebral infarction was significantly related to World Federation of Neurologic Surgeons grade (odds ratio (OR) 1.5/grade, 95% confidence interval (CI) 1.1 to 2.01, p = 0.006) and SAH-Physiologic Derangement Score (PDS) >2 (OR 3.7, 95% CI 1.4 to 9.8, p = 0.01) on admission. Global cerebral oedema (OR 4.3, 95% CI 1.5 to 12.5, p = 0.007) predicted cerebral infarction. Patients with cerebral infarction detectable by day 2 had a higher SAH-PDS than patients with later cerebral infarction (p = 0.025). CONCLUSIONS: Many cerebral infarctions after SAH are unlikely to be caused by vasospasm because they occur too soon after SAH or because angiography shows no vasospasm in a referable artery, or both. Physiological derangement and cerebral oedema may be worthwhile targets for intervention to decrease the occurrence and clinical impact of cerebral infarction after SAH.

Location characteristics of early perihaematomal oedema.

BACKGROUND: The natural history and triggers of perihaematomal oedema (PHO) remain poorly understood. Cerebral amyloid angiopathy (a common cause of lobar haemorrhage) has localised anticoagulant and thrombolytic properties, which may influence PHO. We hypothesised that early (within 24 hours) oedema to haematoma volume ratios are smaller in patients with lobar intracerebral haemorrhage (ICH) than in patients with deep ICH. METHODS: Haematoma and PHO volumes were measured in consecutive patients admitted to an acute stroke unit with a diagnosis of spontaneous supratentorial ICH proven by computed tomography. The oedema to haematoma volume ratios were calculated and compared in patients with lobar ICH and deep ICH. RESULTS: In total, 44 patients with ICH were studied: 19 patients had deep ICH, median haematoma volume 8.4 ml (interquartile range (IQR) 4.8 to 20.8), median PHO 8.2 ml (2.8 to 16), and 25 had lobar ICHs, median haematoma volume 17.6 ml (6.6 to 33.1) and median oedema volume 10.2 ml (3.4 to 24.2). Patients with lobar ICH were older than those with deep ICH (65.7 v 57.4 years, p = 0.009) but ICH location did not differ by sex or race. There was no evidence that haematoma or oedema volumes were related to type of ICH (p = 0.23, p = 0.39 respectively). The median oedema to haematoma volume ratios were similar in patients with lobar and deep ICH (0.67 v 0.58, p = 0.71). Controlling for age, sex, and race made little difference to these comparisons. CONCLUSIONS: There are no major location specific differences in PHO volumes within 24 hours of ICH onset. Deep and lobar ICH may have common therapeutic targets to reduce early PHO.

A systematic review of Terson's syndrome: frequency and prognosis after subarachnoid haemorrhage.

OBJECTIVE: To review systematically the frequency and prognostic significance of vitreous haemorrhage in patients with subarachnoid haemorrhage (Terson's syndrome). METHODS: Papers relating to vitreous haemorrhage in patients with subarachnoid haemorrhage were retrieved. The only studies considered were those with at least 10 consecutive cases of subarachnoid haemorrhage with or without vitreous haemorrhage. The frequency of vitreous haemorrhage in such cases was calculated in prospective and retrospective studies. Mortality was compared in patients with and without Terson's syndrome. RESULTS: 154 papers were reviewed. Three prospective studies and six retrospective studies satisfied the inclusion criteria. Of 181 patients with subarachnoid haemorrhage assessed prospectively (mean age, 51.7 years), 24 (13%) had vitreous haemorrhage; among 1086 retrospective records, 37 (3%) had documented vitreous haemorrhage (p<0.001). Patients with Terson's syndrome had higher Hunt and Hess grades than those without (mean grade, 3.6 v 2.6). Patients with Terson's syndrome were also more likely to die (13 of 30 (43%) v 31 of 342 (9%); odds ratio 4.8; p<0.001). CONCLUSIONS: Prospective studies show a higher frequency of Terson's syndrome than retrospective studies, suggesting that vitreous haemorrhage is not well documented. Vitreous haemorrhage is an adverse prognostic finding in patients with subarachnoid haemorrhage.

Effect of apolipoprotein E genotype on in-hospital mortality following intracerebral haemorrhage.

OBJECTIVE: To determine the relationship between the apolipoprotein E (APOE) epsilon4 allele and in-hospital mortality from intracerebral haemorrhage (ICH). MATERIAL AND METHODS: Patients admitted to two acute stroke units with ICH were prospectively evaluated and APOE genotyped. In-hospital survival was recorded in 176 patients. RESULTS: There were 85 men and 91 women, mean age 68 years. Fifty-two (30%) of the 176 patients died in hospital. After adjusting for sex, age, hospital, and race, increased age (P = 0.009) and the presence of the APOEepsilon4 allele (P = 0.026) significantly reduced in-hospital survival. CONCLUSION: The APOEepsilon4 allele in this population may be associated with poor survival following ICH.

Familial clustering of intracerebral hemorrhage: a prospective study in North Carolina.

Few studies have assessed the frequency of familial clustering in intracerebral hemorrhage (ICH). Of 144 patients with ICH prospectively assessed, 14 (9.8%) had a positive family history of ICH (FH+). Four pedigrees had more than two affected family members. Comparisons between FH+ and FH- probands demonstrated no significant differences in race, age, sex, ICH type or location. An underlying genetic etiology may account for familial clustering in some ICH patients.

Advances in the genetics of cerebrovascular disease and stroke.

MEDLINE searches identified epidemiologic, experimental, and clinical studies on the genetics of cerebrovascular disease and stroke, including the following topics: genetic epidemiology of stroke; genetics of systemic disorders that cause ischemic stroke, including coagulation disorders, connective tissue disorders, vasculopathies, metabolic disorders, and disorders of unknown etiology; and genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries in stroke genetics involve the genetic basis of monogenic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and sickle cell disease. Reproducing similar advances in other forms of cerebrovascular disease and stroke will be more difficult because their inheritance is complex, multigenic, and heterogeneous. However, the future is promising with the application of molecular genetic approaches such as linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses as well as the transmission/disequilibrium test--a statistical method for detection of linkage between a marker and a disease-susceptibility locus.

Use of exponential diffusion imaging to determine the age of ischemic infarcts.

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) detects acute ischemic infarcts with high lesion conspicuity. Determination of infarct age is difficult on DWI alone because infarct signal intensity (SIinfarct) on DWI is influenced by T2 properties ("T2 shine-through"). Maps of the apparent diffusion coefficient (ADC) reflect pure diffusion characteristics without T2 effects but have low lesion conspicuity. Thus, in clinical practice, combined use of DWI and ADC maps is required. Exponential DWI (eDWI) is an innovative means of MRI-diffusion data analysis that merges the advantages of DWI and ADC maps. The authors hypothesized that SIinfarct on eDWI would correlate with infarct age. The authors studied 114 consecutive patients who had 120 ischemic strokes with clearly determined onset times and who underwent echo-planar DWI. The eDWI were generated by dividing the signal intensity on DWI by that on the corresponding T2 image on a pixel-by-pixel basis. SIinfarct on eDWI was measured in the lesion core and expressed as a percentage of contralateral control tissue. On eDWI, relative SIinfarct changed significantly with infarct age (P < .0001). When patients were sorted in infarct-age groups, no significant differences were found within the first 120 hours. However, for patients studied within 5 days, the mean relative SIinfarct was significantly higher compared with patients studied > or = 8 days after stroke (P < .05). For all infarcts up to 5 days old, the eDWI signal intensity was higher than control tissue (hyperintense appearance). All infarcts > 10 days old had an eDWI signal intensity lower than control tissue (hypointense appearance). The authors concluded that the use of eDWI, as a single set of images, reliably differentiates acute infarcts (< or = 5 days old) from infarcts > 10 days old. This feature would be expected to be helpful when the distinction between acute and nonacute infarction cannot be determined on clinical grounds.

Suppression of recurrent transient ischemic attacks by a statin agent.

Recent studies of hydroxy-methylglutaryl coenzyme A reductase inhibitors have demonstrated that therapy with statins is associated with a significant decrease in the risk of stroke and TIA in patients with coronary artery disease. The underlying mechanism responsible for this effect is unclear. The author presents two patients who had cessation of TIAs upon institution of statin therapy. A variety of non-lipid-lowering mechanisms may account for this beneficial effect. This initial observation, if confirmed by further study, may suggest a role for statin agents in preventing recurrent TIAs.

Treatment of acute ischemic stroke.

Acute ischemic stroke remains difficult to treat despite the advent of new therapies. The only approved medication to reverse its effects is recombinant tissue plasminogen activator administered intravenously within 3 hours of onset of stroke symptoms--an opportunity that does not often present itself. The principal drawback to thrombolytic therapy for acute ischemic stroke is a 3% to 6% occurrence of symptomatic cerebral hemorrhage. Although intra-arterial recombinant prourokinase also appears to be effective, it has not been approved by the Food and Drug Administration. Aspirin administered within 48 hours of stroke onset can prevent a few recurrent strokes and deaths. The efficacy of heparin and heparinoids in acute ischemic stroke has not been shown. Despite their theoretical attractiveness and laboratory results, neuroprotective agents have not proven effective in clinical trials. In view of current limitations on the ability to treat and reverse the effects of acute ischemic stroke, improved preventive measures in patients at risk for stroke are urgently needed.

Recommendations for the establishment of primary stroke centers. Brain Attack Coalition.

OBJECTIVE: To develop recommendations for the establishment and operation of primary stroke centers as an approach to improve the medical care of patients with stroke. PARTICIPANTS: Members of the Brain Attack Coalition (BAC), a multidisciplinary group of representatives from major professional organizations involved with delivering stroke care. Supplemental input was obtained from other experts involved in acute stroke care. EVIDENCE: A review of literature published from 1966 to March 2000 was performed using MEDLINE. More than 600 English-language articles that had evidence from randomized clinical trials, meta-analyses, care guidelines, or other appropriate methods supporting specific care recommendations for patients with acute stroke that could be incorporated into a stroke center model were selected. CONSENSUS PROCESS: Articles were reviewed initially by 1 author (M.J.A.). Members of the BAC reviewed each recommendation in the context of current practice parameters, with special attention to improving the delivery of care to patients with acute stroke, cost-effectiveness, and logistical issues related to the establishment of primary stroke centers. Consensus was reached among all BAC participants before an element was added to the list of recommendations. CONCLUSIONS: Randomized clinical trials and observational studies suggest that several elements of a stroke center would improve patient care and outcomes. Key elements of primary stroke centers include acute stroke teams, stroke units, written care protocols, and an integrated emergency response system. Important support services include availability and interpretation of computed tomography scans 24 hours everyday and rapid laboratory testing. Administrative support, strong leadership, and continuing education are also important elements for stroke centers. Adoption of these recommendations may increase the use of appropriate diagnostic and therapeutic modalities and reduce peristroke complications. The establishment of primary stroke centers has the potential to improve the care of patients with stroke. JAMA. 2000.

Recent advances in stroke management.

Major advances in stroke treatment and prevention have, occurred over the last several years. Recent studies have documented that appropriate modification of stroke risk factors can lead to, a substantial reduction in stroke incidence. In addition, a variety of new risk factors, such as elevated plasma homocysteine levels, antiphospholipid antibodies, and specific genetic factors, are being recognized. The most significant advance in acute stroke therapy is the use of intravenous tissue plasminogen activator, (t-PA) for treatment of patients with ischemic stroke within 3 hours of symptom onset. T-PA is currently the only stroke treatment approved by the Federal Drug Administration. There continues to be uncertainty and misunder-standing regarding the risks and benefits of this therapy. A variety of neuroprotective agents have been highly successful for reducing ischemic brain injury in animal stroke models. Recent clinical trials with these agents, however, have not produced beneficial effects in humans. Newer neuroprotective agents with more favorable safety profiles and improvements in clinical trial design may lead to therapeutic successes in the near future. It is apparent that both thrombolytic and neuroprotective treatments for acute stroke must be administered very rapidly, after stroke onset. Therefore, acute stroke teams are being developed to facilitate rapid diagnostic evaluation and treatment of stroke patients.

Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes.

We investigated whether early hematoma or edema volumes could explain the adverse association between APOE epsilon4 and survival in intracerebral hemorrhage. Among 102 patients, epsilon4 carriers had a higher mortality rate than non-epsilon4 carriers (38 versus 24%, p = 0.05). Nonsurvivors had larger hematoma (75.5 cm3 versus 27.1 cm3, p<0.001) and edema volumes (37.5 cm3 versus 17.1 cm3, p<0.01), but these were not associated with epsilon4 after adjusting for race, age, and type of hemorrhage.