Drug products: Actilyse, Actilyse®
ATC code: B01AD02
Alteplase is mainly used in ischemic stroke but also in some cases of myocardial infarction and pulmonary embolism.
The risk of symptomatic intracranial hemorrhage after thrombolysis of ischemic stroke has in observational studies been found to be slightly higher in men. In treatment of myocardial infarction women were shown to have a higher risk of bleeding complications. In myocardial infarction a standard dose is used while the dosage in ischemic stroke is calculated by per kilogram body weight usually resulting in lower doses for women.
No studies with a clinically relevant sex analysis regarding pharmacokinetics of alteplase have been found. Dosing is done after weight [1, 2]. Compared to other countries, a lower dose is registered for both men and women in Japan .
Meta-analyses of sex differences in placebo-controlled trials of i.v. rt-PA with alteplase 0-6 h after onset of ischemic stroke have been conducted. In one  (1 190 men, 980 women) the odds of good outcome, defined as independence in daily living, was found to be better in men than in women on placebo, while there was no sex difference in patients treated with alteplase [2, 3]. Another meta-analysis of observational studies on outcomes after i.v. rt-PA (12 620 men, 5 221 women) found no sex difference in alteplase treated patients , a finding which has been confirmed in other studies [5-7].
Studies not included in the meta-analyses, analyzing sex differences in outcome after i.v. thrombolysis with alteplase for acute ischemic stroke, report contradictory results. Some studies suggest that women benefit more than men from alteplase treatment [8-12], while others suggest a worse outcome in women [13-16], or no sex differences [6, 17-22].
Using the Safe Implementation of Stroke (SITS), a register of thrombolysis with alteplase in ischemic stroke, several analyses on sex differences have been performed. Based on this material (25 777 men, 19 302 women) multivariate analysis showed male sex to be correlated to symptomatic intracranial hemorrhage and higher mortality (OR 1.19) . In another analysis (43 056 men, 18 412 women) women were found to have a higher adjusted odds ratio for remote intracranial hemorrhage than hemorrhages in the infarction area (adjusted OR 1.23) .
The Global Utilization of Streptokinase and t-PA in Occluded Coronary Artery (GUSTO-I) study (30 600 men, 10 292 women) investigated accelerated alteplase combined with heparin as one of several thrombolytic substances used in acute myocardial infarctions. In contrast to the findings in SITS, female sex together with lower body weight and older age were found in multivariate analyses to be the independent strongest predictors of bleeding complications after thrombolysis [24, 25]. Higher doses of alteplase have in general been used in myocardial infarctions . In ischemic stroke the dose used is 0.9 mg/kg and never >90 mg , in myocardial infarctions an alteplase dose of 100 mg is normally used and in the GUSTO trial the accelerated dose regiment was <100 mg or 100 mg.
A retrospective study of alteplase in ischemic stroke (59 men, 54 women) found no sex differences in the incidence of intracranial or peripheral bleeding .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
An older meta-analysis study found women to be less likely to be treated with i.v. rt-Pa for ischemic stroke (OR 0.7) . The heterogeneity of the studies in this analysis was large. Possible explanations are the time at which the study was performed and whether thrombolysis had indication in patients > 80 years. Women are in general older at onset of stroke and indication in patients >80 years was unclear until 2012 when the randomized, placebo-controlled, unblinded study IST-3 (1 465 men, 1 570 women, in all 53% >80 years) could show a positive effect also in older stroke patients .
Date of litterature search: 2019-03-04
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson