Favourable clinical outcomes, lower sICH with low-dose alteplase in patients with prior antiplatelet therapy
The use of low-dose intravenous (IV) alteplase may be associated with more favourable clinical outcomes and lower risk of symptomatic intracerebral haemorrhage (sICH) in thrombolysis-treated acute ischaemic stroke patients who previously received antiplatelet therapy (APT) compared with the standard dose, according to the ENCHANTED* trial.
This multicentre, prospective, blinded-end point trial included 3,285 patients (mean age 66.6 years, 38 percent women). The 752 patients who reported prior APT use were randomized to receive low-dose (0.6 mg/kg, n=407) or standard-dose (0.9 mg/kg, n=345) IV alteplase within 4.5 hours of symptom onset.
Although not significant, low-dose alteplase resulted in a more favourable 90-day clinical outcome than standard-dose alteplase in patients with APT history vs those without prior APT based on mRS (modified Rankin Scale) scores 2–6 (odds ratio [OR], 0.84 vs OR, 1.16; p-trend=0.053), mRS scores 3–6 (OR, 0.80 vs OR, 1.10; p-trend=0.065), or ordinal mRS shift (OR, 0.76 vs OR, 1.07; p interaction=0.023). [Stroke 2017;48:1877-1883]
Based on the SITS-MOST** criteria, prior APT use was associated with an increased sICH risk (adjusted OR, 1.82, 95 percent CI, 1.00–3.30; p=0.051), which decreased in patients given low-dose vs standard-dose alteplase (OR, 0.38, 95 percent CI, 0.14–1.02).
“Patients on prior APT … are at significantly higher risk of sICH and poor outcome compared with other patients who receive alteplase,” said the researchers. “[T]his may be considered an important treatment option in such patients.”
The researchers highlighted that while the numbers are ‘too small’ to offer a reliable risk assessment based on varying doses of alteplase, some study protocols have recommended the avoidance of APT for at least 24 hours after alteplase use. [Stroke 2013;44:870-947; Cochrane Database Syst Rev 2014;7:CD000213]
Overall, although nonsignificant, the results suggest a trend towards better clinical outcomes with low-dose vs standard-dose alteplase, said the researchers, who called for randomized trials to elucidate the effects of low-dose and standard-dose alteplase in patients with APT history.
The potential benefits of low-dose alteplase in patients with high sICH risk should also be further investigated, they added.