Off-Label Thrombolysis Is Not Associated With Poor Outcome in Patients With Stroke

Abstract

Background and Purpose-Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. Methods-All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (nϭ1104). After excluding basilar artery occlusions (nϭ119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. Results-One or more license contraindications to thrombolysis was present in 51% of our patients (nϭ499). The most common of these were age Ͼ80 years (nϭ159), mild stroke National Institutes of Health Stroke Scale score Ͻ5 (nϭ129), use of intravenous antihypertensives prior to treatment (nϭ112), symptom-to-needle time Ͼ3 hours (nϭ95), blood pressure Ͼ185/110 mm Hg (nϭ47), and oral anticoagulation (nϭ39). Age Ͼ80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. Conclusions-Off-license thrombolysis was not associated with poorer clinical outcome, except for age Ͼ80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available. (Stroke.

Effectiveness and Safety of Thrombolysis in Ischemic Stroke Patients Aged 80 Years or Older

“…34,35 Although the sHT rate in the elderly who were given thrombolysis was higher than in the younger in our study, as previously reported, 11,12,17,19 neither the adjusted ORs were apparently different (5.27 in the aged ≥80 and 4.52 in the aged <80), nor there was signifi cant interaction between age group and thrombolysis (P=0.86). The VISTA group did not report the analysis results about sHT.…”

“…[19][20][21] For making evidence, a randomized controlled trial for thrombolysis to the elderly stroke patients is the best choice, but it has not been reported yet.…”

Adherence to Third European Cooperative Acute Stroke Study 3- to 4.5-Hour Exclusions and Association With Outcome

“…[6][7][8][9][10][11][12][13][14][15] There are also now randomized trial data from the Third International Stroke Trial (IST-3), which enrolled patients for whom there was equipoise regarding the benefits of thrombolytic therapy and randomized to treatment with IV tPA versus placebo ≤6 hours from onset. 16 This study included 1617 patients aged >80 years and found that although the rate of good outcome in that group was overall lower than younger patients, there was still a significant benefit to treatment with IV tPA.…”

Stroke occurring in patients with cognitive impairment or dementia

“…The license of intravenous recombinant tissue plasminogen activator (rt-PA) in the European Union is restricted to patients aged 80 years or less in many countries, but most centres do not follow this rule anymore 37 . According to the results from the 3 rd International Stroke Trial 38 and the updated meta-analysis 39 that proved the efficacy of rt-PA in patients aged 80 years or more, the use of rt-PA for elderly patients in clinical practice has increased.…”