According to the American Heart Association (AHA) guidelines, the safety of intravenous (IV) alteplase in patients on direct oral anticoagulants (DOACs) remains debatable. Moreover, IV alteplase should not be considered in such population unless all laboratory values (aPTT, INR, thrombin time, platelet count, ecarin clotting time, or other appropriate factor Xa assays) return normal, or it has been > 48 hours since the last dose of DOAC administration (assuming normal renal function). This recommendation is expert consensus based on clinical experiences. [1]
It is stated that, although the guidelines recommend using aPTT, INR, TT, PT, and/or ECT to monitor the effect of anticoagulation to determine the eligibility for alteplase, these measurements are qualitative but are often inadequate in reliably quantifying the effect of anticoagulation of non-vitamin K oral anticoagulants (NOACs; e.g., dabigatran, apixaban, rivaroxaban). Moreover, there is no clinical data available regarding when is the optimal time to restart NOACs after acute ischemic stroke. [2]
In a review of 55 studies, 492 patients NOACs (dabigatran, apixaban, rivaroxaban, non-specified NOAC) who received IV tPA for acute stroke were identified. The included population was elderly (median age 77; interquartile range [IQR] 68-83) with median National Institutes of Health Stroke Scale score of 10 (IQR 6-16). The median time from last NOAC intake to stroke onset was 8 hours (IQR 2.5-14.5). The majority of the patients took NOAC within 12 hours of stroke onset (55.2%; 80/145). About a third took NOAC 13-24 hours (33.7%; 43/127), and 7.7% (10/130) took >24 hours preceding stroke onset. aPTT was the most commonly used coagulation test, and 27.4% (34/124) had prolonged aPTT levels. Other reported lab data are prolonged PT (7/16; 43.8%); prolonged TT in dabigatran (23/27 85.2%); TT, dTT, dabigatran concentration in dabigatran (37/94; 39.4%); and anti-Xa assays in rivaroxaban or apixaban (43/91; 47.3%). Of note, baseline characteristics information was not available for all patients. For clinical outcomes, the rate of sICH was reported in 4.3% (20/462), death was reported in 11.3% (48/423), and favorable outcomes were reported in 43.7% (164/375) patients. Favorable outcomes are defined as NIHSS, ≤1; mRS, 0–2; or improvement in NIHSS score, ≥8 points. Among those taking dabigatran, reversal with idarucizumab was associated with more favorable outcomes (79.1% [34/43] vs. 39.2% [29/74]; unadjusted OR 5.86; 95% CI, 2.45–14.00). There was no significant difference in the rate of sICH (unadjusted OR 0.60; 95% CI 0.12-2.92) or death (unadjusted OR 0.35; 95% CI 0.08-1.61). The authors conclude that IV tPA for acute ischemic stroke in patients receiving NOAC appears to be feasible without significant bleeding risks. There are several limitations to this review. First, the data were collected from case reports or case series, and some data were incomplete (e.g., baseline characteristics). There was no control group and pooled analysis was not performed; therefore, risk assessment data are not available. Finally, the study included patients on various NOAC, but the effects of individual NOACs were not reported/compared to each other. [3]
In a meta-analysis that evaluated data from 52,823 stroke patients, 366 patients were taking DOAC (warfarin: n= 2,133; no previous anticoagulation: n= 50,324). The study reported that, compared to warfarin, receiving a DOAC during the last 48 hours before bolus tPA was not associated with an increased risk of symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis (IVT) treatment [Odds ratio (OR) sICH according to NINDS definition: 0.53 [95% CI, 0.18–1.52]; OR for sICH according to ECASS-II definition: 0.77 [95% CI, 0.28–2.16]. In addition, the risk of sICH did not differ when compared to those with no history of anticoagulation (OR for sICH according to NINDS definition: 1.23 [95% CI, 0.46–3.31]; OR for sICH according to ECASS-II definition: 0.92 [95% CI, 0.33–2.55]). The results did not change when analyses were performed with no time limit. Compared to warfarin, the risk of sICH in those pretreated with a DOAC before tPA was OR: 0.85 [95% CI, 0.49–1.45] sICH according to NINDS definition; ECASS-II definition: OR 1.11 [95% CI, 0.67–1.85]. Compared to no previous anticoagulation, the risks were OR 1.17 [95% CI, 0.43–3.15] sICH according to NINDS definition; ECASS-II definition: 0.87 [95% CI, 0.33–2.41]]. For all data, there were no significant concerns for data heterogeneity (I2 = 0). [4]