Alteplase Is Safe Beyond Three-Hour Treatment Window for Stroke
Alteplase can be administered safely three to 4.5 hours after the onset of ischemic stroke, according to a study in the September 12 online Lancet.
Nils Wahlgren, MD, of the Karolinska University Hospital in Stockholm, and colleagues included 11,865 patients who were given IV alteplase (0.9 mg/kg total dose) within the preferred three-hour treatment window after stroke onset and 664 patients who received the drug from three to 4.5 hours. All patients were from the Safe Implementation of Treatments in Stroke database. Outcome measures were symptomatic intracerebral hemorrhage within 24 hours (hemorrhage type 2 associated with NIH Stroke Scale [NIHSS] score of ≥ 4 points deterioration) and mortality and independence (modified Rankin Scale score of 0 to 2 points) at three months.
Among patients who received alteplase from three to 4.5 hours, treatment was begun a median of 195 minutes after symptom onset, the median age was 65, and the median NIHSS score was 11. For patients who received alteplase within three hours, treatment was begun a median of 140 minutes after symptom onset, the median age was 68, and the median NIHSS score was 12.
Results from both cohorts were similar regarding the outcome measures—1.6% of patients treated within three hours had intracerebral hemorrhage, compared with 2.2% of those who received delayed treatment. Of those who were treated with alteplase within the three-hour window, 58% were able to resume their daily routine after recovery, compared with 56.3% of those who were treated more than three hours after symptom onset. In addition, the mortality rate differed only slightly between the two groups—12.2% for those treated within three hours versus 12.7% for those who received delayed treatment.
“Our results show that the rates of symptomatic intracerebral hemorrhage, mortality, and independence at three months follow-up in routine clinical practice are similar between patients for whom treatment was started between three hours and 4.5 hours and for those treated within three hours after ischemic stroke,” reported the researchers.
The investigators added that their findings “should not slow efforts to facilitate rapid treatment, since the time-dependent benefit from thrombolysis seen in the analysis from pooled data from randomized controlled trials requires that systems be optimized for the earliest possible delivery of alteplase.”
Wahlgren N, Ahmed N, Dávalos A, et al. Thrombolysis with alteplase 3–4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008 Sep 12; [Epub ahead of print].
Antipsychotic Exposure Increases the Risk of Stroke for Dementia Patients
Antipsychotics are associated with an increased risk of stroke, and this risk is highest in patients receiving atypical antipsychotics and in those with dementia, reported researchers in the August 28 BMJ.
Patients with recorded incident stroke who were prescribed at least one antipsychotic drug before the end of 2002 were identified from the General Practice Research Database in the United Kingdom by Ian J. Douglas, MSc, PhD, and Liam Smeeth, MBchB, MRCGP, FFPH, MSc, PhD, from the London School of Hygiene and Tropical Medicine.
The most commonly used typical antipsychotics were phenothiazines, and the most common atypical antipsychotic was risperidone. The median age of first exposure to any of these drugs was 80. The median age at the time of first recorded stroke was 81.
Of 6,790 eligible patients, those who had a diagnosis of dementia before incident stroke totaled 1,423. Typical antipsychotics only were prescribed for 5,885 subjects, atypical antipsychotics only were prescribed for 456 subjects, and both typical and atypical antipsychotics were prescribed for 449 subjects. “Among patients with dementia, 1,212 received only typical antipsychotics and 85 received only atypical antipsychotics,” noted the researchers. The median total observation period was at least four years in each group.
The rate ratio for stroke among all patients prescribed any antipsychotic medication was 1.73, when comparing exposed with unexposed baseline periods. During exposed periods, the rate ratio was 1.69 for patients receiving only typical antipsychotics and 2.32 for patients receiving only atypical antipsychotics. The rate ratio during treatment periods with any antipsychotic was 3.50 in patients with dementia prior to stroke and 1.41 in patients with no recorded dementia. Subjects with dementia who were treated with atypical antipsychotic medications had a higher rate ratio for stroke (5.86) than those with dementia who took typical antipsychotics (3.26). The rate ratio was also higher for patients without dementia who received only atypical antipsychotics (1.90) than those without dementia who had received only typical antipsychotics (1.40). In all subgroups, the rate ratio fell toward unity during the phase after treatment.
The modest association between antipsychotics and stroke in patients without dementia suggests that “the use of antipsychotics might be acceptable in elderly patients without dementia, although as with all treatment choices, a wider consideration of all potential risks and benefits would need to be taken into account,” the study authors concluded.
Douglas IJ, Smeeth L. Exposure to antipsychotics and risk of stroke: self controlled case series study. BMJ. 2008;337:a1227.