PATIENTS WITH MILD STROKE SYMPTOMS STILL NEED T-PA

A substantial portion of patients deemed “too good to treat” with intravenous tissue plasminogen activator (t-PA) experience poor outcomes, according to a report in the November Stroke. Eric E. Smith, MD, and colleagues suggested that “a reevaluation of the stroke severity criteria for t-PA eligibility may be indicated.”

The researchers retrospectively analyzed data on 431 “too good to treat” patients—those arriving within three hours of symptom onset and not treated with intravenous t-PA because they exhibited mild or improving symptoms.

Of 128 patients who arrived at the emergency department within three hours of symptom onset, 41 were not given t-PA because they had mild or improving symptoms. In 21 of the 41 patients, National Institutes of Health Stroke Scale (NIHSS) score improved by 1 or more points from emergency department arrival to decision to treat with t-PA. Stable mild stroke symptoms were observed in 20 of the 41 patients.

Of the “too good to treat” patients, 11 died or were not discharged home because of neurologic worsening or persistent mild neurologic deficit, according to the researchers. Patients with persistent neurologic deficit had cognitive impairment, gait impairment attributable to hemiparesis, or ataxia. The researchers observed that “too good to treat” patients were less likely to have vascular occlusion and more likely to have strokes attributable to small vessel infarction, compared with patients who were treated with t-PA. “Unfortunately we were unable to find any features that could predict which of the untreated patients would have problems,” Dr. Smith commented.

“Right now we can only recommend that physicians be a little more cautious in deciding against t-PA treatment,” said Dr. Smith. “We can suggest that more attention be paid to patients’ ability to walk—something that often is not evaluated—since gait disturbance was a reason why several could not go home. But we really need to find ways to predict who will do poorly without t-PA, and for that we’ll need larger trials involving several institutions.” The research team noted that additional studies are needed before any recommendations for alterations of current practice can be made.

Smith EE, Abdullah AR, Petkovska I, et al. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke. 2005;36:2497-2499.

ATYPICAL ANTIPSYCHOTICS INCREASE RISK OF DEATH IN PATIENTS WITH DEMENTIA

Patients with dementia who receive atypical antipsychotic drugs for the treatment of aggression, delusions, and other neuropsychiatric symptoms are at an increased risk of death, according to a study in the October 19 JAMA.

Lon S. Schneider, MD, MS, and colleagues conducted a meta-analysis of 15 trials (nine unpublished), generally 10 to 12 weeks in duration, comparing atypical antipsychotic drugs with placebo—aripiprazole, olanzapine, quetiapine, and risperidone were assessed in three, five, three, and five of the 15 trials, respectively. Two trials also compared the effect of haloperidol, a first-generation antipsychotic drug, on mortality. Overall, 87% of study participants had Alzheimer’s disease. A total of 3,353 patients were randomized to antipsychotic drugs, while 1,757 were randomized to placebo.

Dr. Schneider and his colleagues found that death occurred more frequently in patients who received antipsychotic drugs (3.5%) than in patients who received placebo (2.3%). The odds ratio for death in patients treated with antipsychotic drugs was 1.54. “Sensitivity analyses did not show evidence for differential risks for individual drugs,” they said. Furthermore, no differences in risk of death were observed between those with higher cognitive function and those with lower cognitive function.

The researchers also noted that patients who received the first-generation antipsychotic haloperidol had an increased risk of death (risk ratio, 2.07). “This suggests that increased mortality is a risk for all first- and second-generation antipsychotic drugs when they are used to treat the neuropsychiatric symptoms of dementia,” said Peter V. Rabins, MD, MPH, and Constantine G. Lyketsos, MD, MHS, in an accompanying editorial.

“These findings emphasize the need to consider certain changes in some clinical practices. Antipsychotic drugs have been dispensed fairly frequently to patients with dementia and used for long periods. The established risks for cerebrovascular adverse events together with the present observations suggest that antipsychotic drugs should be used with care in these patients,” said the researchers.

“The results do not contraindicate the use of antipsychotic drugs in the treatment of patients with dementia who have psychotic symptoms and agitation; instead, they change the risk-benefit analysis such that antipsychotic drugs should be used only when there is an identifiable risk of harm to the patient or others, when the distress caused by the symptoms is significant, or when alternate therapies have failed and symptom relief would be beneficial,” said Drs. Rabins and Lyketsos.

Rabins PV, Lyketsos CG. Antipsychotic drugs in dementia: what should be made of the risks? JAMA. 2005;294:1963-1965.
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294:1934-1943

OBSTRUCTIVE SLEEP APNEA INCREASES THE RISK OF STROKE AND DEATH

Patients with obstructive sleep apnea are at an increased risk of stroke or death from any cause, according to H. Klar Yaggi, MD, MPH, and colleagues. This association was independent of other risk factors, including hypertension. A report of their findings was published in the November 10 New England Journal of Medicine.

The study involved 1,022 people 50 or older who were referred to the Yale Center for Sleep Medicine. All patients underwent at least two hours of polysomnography and completed a 10-page questionnaire on their sleep and medical history. Patients with a sleep-hypopnea index of less than 5 served as controls. Sixty-eight percent of the patients were classified as having obstructive sleep apnea.

According to the researchers, the mean apnea-hypopnea index among patients with obstructive sleep apnea was 35, compared with 2 in the control group. Patients with obstructive sleep apnea had a higher prevalence of hypertension and diabetes mellitus and had a higher body mass index, lower nadir oxygen saturations, and higher arousal index.

A large number of patients with obstructive sleep apnea received treatment for sleep apnea after the initial evaluation. Thirty-one percent of patients reduced their weight by 10% or more, 58% were using airway pressurization for at least four hours per night for five nights or more per week, and 15% underwent upper airway surgery, the investigators reported.

More than three years after the initial evaluation, data on stroke events and death from any cause were available for only 842 patients. Although the researchers were unable to contact the remaining patients, vital records did not indicate they had died.

Dr. Yaggi’s group found that incident stroke or death occurred in 9% of patients. There were 22 strokes and 50 deaths in the obstructive sleep apnea group, compared with two strokes and 14 deaths in the control group. Patients with obstructive sleep apnea were 2.24 times more likely to have a stroke or to die than were patients without the syndrome. This association remained statistically significant even after adjustment for age, gender, race, smoking status, alcohol consumption status, body mass index, and the presence or absence of diabetes mellitus, hyperlipidemia, atrial fibrillation, and hypertension.

The researchers also found that patients in the quartile with the most severe sleep apnea had a threefold increased risk of stroke or death from any cause.

Yaggi HK, Concato J, Kernan WN, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034-2041.

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