Comparative effects of low-dose versus standard-dose alteplase in ischemic patients with prior stroke and/or diabetes mellitus: The ENCHANTED trial

Background and purpose: History of prior stroke (PS) and diabetes mellitus (DM) are considered relative contraindications to the use of intravenous alteplase in patients with acute ischemic stroke (AIS). We aimed to assess whether a history of PS and DM modified the comparative effects of low- versus standard-dose alteplase in patients who participated in the alteplase-dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: Data from an international, multi-center, prospective, randomized, open-label, blinded-endpoint trial were used to assess the benefits and risks of low (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in thrombolysis-eligible AIS patients. Logistic regression was used for analysis of patient subgroups defined by history of PS and DM on efficacy and safety outcomes, adjusted for confounding variables. Results: After adjusting for baseline characteristics and management variables over the first seven days in 3288 AIS patients (431 PS, 489 DM, and 157 with both), history of PS and DM were not associated with poor outcome at 90-days: whether defined by modified Rankin scale (mRS) scores 2–6 (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.55–1.32; P = 0.476) or mortality (OR 1.25, 95%CI 0.62–2.52; P = 0.533). There was no differential effect of low-versus standard-dose alteplase on dichotomized mRS (0–1 vs. 2–6), ordinal shift in mRS scores, mortality, or symptomatic intracerebral hemorrhage, by a history of PS and DM. Conclusions: A history of PS and DM was not an independent predictor of poor outcome in thrombolysis-treated AIS patients. We were not able to demonstrate any effect of these variables in modifying the differences in effects of low- versus standard-dose alteplase. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.