those who have persistent elevations in BP despite administration of bolus thera­pies, or if contraindications such as bradycardia prohibit labetalol administration, a continuous infusion of nicardipine is often considered. Comparative trials of labet­alol and nicardipine are limited in their retrospective design but appear to suggest that an up-front approach with administration of nicardipine may result in improved time to target BP control and lower BP variability with no increased incidence of adverse effects [56–58]. Clevidipine is an alternative dihydropyridine calcium chan­nel blocker with similar pharmacologic activity as nicardipine but differs in its for­mulation in a lipid emulsion and shorter half-life, which allows for more rapid titration. Head-to-head comparisons between clevidipine and nicardipine suggest similar efcacy in terms of blood pressure reduction but a lower overall volume administered with clevidipine, which may be advantageous in those at risk for vol­ume overload [59, 60]. Hydralazine is a potent, direct-acting vasodilator that is fre­quently employed as an alternative to labetalol if an IVP agent is needed. However, hydralazine has been shown to increase intracranial pressure and decrease perfusion pressure, which can be deleterious in the setting of ischemia [61]. Furthermore, patient response to hydralazine is often unpredictable and its effects are prolonged, which can lead to precipitous drops in BP with a high degree of variability. The AHA/ASA guidelines suggest that hydralazine may be considered an alternative if other agents are unavailable or otherwise contraindicated [7]. Enalaprilat is the intravenous active metabolite of the angiotensin-converting enzyme inhibitor enala­pril. Enalaprilat should be used with caution in AIS given its prolonged duration of action, which can prohibit titration and increase the risk of angioedema with ACE inhibitors when administered concomitantly with alteplase [62].

Investigations into early initiation of anticoagulation in non-cardioembolic acute ischemic strokes have been performed under the hypothesis that anticoagulation could reduce thrombus propagation, decrease the volume of infarcted tissue, and thus reduce the degree of neurologic decits. A systematic review including 28 tri­als of over 24,000 participants treated with unfractionated heparin, low-molecular­weight heparin, oral anticoagulants, or direct thrombin inhibitors failed to nd any change in rates of disability or dependence (OR 0.98, 95% CI 0.92–1.03) [25]. While most of this data was based on initiation within the rst 48h from symptom onset, these ndings remained consistent even when anticoagulation was initiated within 14days. Although early anticoagulation reduced the rates of early recurrent strokes (0.75, 95% CI 0.65–0.88), this benet was outweighed by the heightened risk of symptomatic intracranial (OR 2.47, 95% CI 1.90–3.21) and extracranial hemorrhagic events (OR 2.99, 95% CI 2.24–3.99) [63]. Thus, routine use of thera­peutic anticoagulation outside of cardioembolic strokes is not recommended.

0.55–0.84) with no signicant difference in hemorrhagic events or all-cause mortal­ity (p= 0.20). Cumulatively, these ndings suggest that early initiation of antico­agulation in cardioembolic stroke may be safe and reduce the risk of recurrent ischemic events but requires a tailored approach based on stroke severity and patient-specic variables that would impact hemorrhage/stroke risk [70].

acute ischemic stroke guidelines [7]. While the studied doses of aspirin in this con­text ranged from 160 to 300mg, lower starting doses (i.e., 81mg) are reasonable. In patients without enteral access, rectal aspirin 300mg can be administered in the place of enteral aspirin.

of symptom onset has a class IA recommendation in the 2019 acute stroke guide­lines [7]. Each of the major trials (CHANCE [81], POINT [82], THALES [73], CHANCE2 [83], and INSPIRES [84]) has minor differences and is summarized in Table17.8. Two trials (THALES and CHANCE2) have evaluated ticagrelor instead of clopidogrel as the backbone of DAPT; ticagrelor produces a similar effect size to clopidogrel with more bleeding, except in the case of CYP2C19 loss of function, where ticagrelor has been demonstrated to be superior to clopidogrel for recurrent stroke prevention. In addition to minor stroke and major TIA, DAPT with full-dose aspirin (325mg) is also recommended in the case of documented intracranial ath­erosclerosis as the etiology of stroke based on the results of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial [85].

started on DAPT for secondary stroke prevention in a cohort of Italian patients did not meet the inclusion criteria of the major trials [86]. While time to initiation of up to 72h has now been demonstrated to be effective (INSPIRES trial), initiation of DAPT after receipt of a thrombolytic or thrombectomy and in more severe strokes has limited supporting evidence. The Antiplatelet vs. R-tPA for Acute Mild Ischemic Stroke (ARAMIS) trial randomized 760 patients presenting with mild stroke within

4.5h of symptom onset to either clopidogrel-based DAPT or alteplase 0.9mg/kg and demonstrated similar rates of excellent functional outcomes at 90days (RR