See Table XCV in online Data Supplement 1 for original wording. 3.9. Antiplatelet Treatment 3.9. Antiplatelet Treatment COR LOE New, Revised, or Unchanged Administration of aspirin is recommended in patients with AIS within 24 to 48 hours after onset. For those treated with IV alteplase, aspirin administration is generally delayed until 24 hours later but might be considered in the presence of concomitant conditions for which such treatment given in the absence of IV alteplase is known to provide substantial benefit or withholding such treatment is known to cause substantial risk. I A Recommendation revised from 2013 AIS Guidelines. The safety and benefit of aspirin in the treatment of patients with AIS were established by 2 large clinical trials This has recently been confirmed by a large Cochrane review of aspirin trials.209 In patients unsafe or unable to swallow, rectal or nasogastric administration is appropriate. Limited data exist on the use of alternative antiplatelet agents in the treatment of AIS. However, in patients with a contraindication to aspirin, administering alternative antiplatelet agents may be reasonable. A retrospective analysis of consecutive ischemic stroke patients admitted to a single center in Seoul, South Korea, found no increased risk of hemorrhage with early initiation of antiplatelet or anticoagulant therapy (<24 hours) after IV alteplase or EVT compared with initiation >24 hours.177 However, this study may have been subject to selection bias, and the timing of initiation of antiplatelet therapy or anticoagulation should be made on an individual level, balancing risk and benefit. The recommendation was modified from the previous guideline to remove the specific dosing recommendation initial dose is 325 mg because previous clinical trials supporting its use for AIS included doses of 160 to 300 mg. See Tables XLII and XLVIII in online Data Supplement 1.


The recommendation was modified from the previous guideline to remove the specific dosing recommendation initial dose is 325 mg because previous clinical trials supporting its use for AIS included doses of 160 to 300 mg. See Tables XLII and XLVIII in online Data Supplement 1. Powers et al 2019 Guidelines for Management of AIS e377 In patients presenting with minor noncardioembolic ischemic stroke (NIHSS score 3) who did not receive IV alteplase, treatment with dual antiplatelet therapy (aspirin and clopidogrel) started within 24 hours after symptom onset and continued for 21 days is effective in reducing recurrent ischemic stroke for a period of up to 90 days from symptom onset. I A New recommendation. Two independent multicenter, randomized, double-blind, placebo-controlled trials have established the efficacy of short-term dual antiplatelet therapy to prevent recurrent ischemic stroke in patients with minor stroke or high-risk TIA. The CHANCE trial (Clopidogrel in High Risk Patients With Acute Nondisabling Cerebrovascular Events; N=5170) conducted in China studied the efficacy of short-term dual antiplatelet therapy begun within 24 hours in patients with minor stroke (NIHSS score 3) or high-risk TIA (ABCD2 [Age, Blood Pressure, Clinical Features, Duration, Diabetes] score 4). The dosing regimen was clopidogrel at an initial dose of 300 mg followed by 75 mg/d for 90 days plus aspirin at a dose of 75 mg/d for the first 21 days or placebo plus aspirin (75 mg/d for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1.


All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome of recurrent stroke at 90 days (ischemic or hemorrhagic) favored dual antiplatelet therapy over aspirin alone: hazard Post hoc analysis found a small but measurable reduction in poor functional outcome (mRS score 2 6) on dual antiplatelet therapy compared with aspirin alone (absolute RR, 1.7% However, a post hoc time-course analysis showed that the benefit in reducing recurrent ischemic stroke compared with the risk of bleeding on dual antiplatelet therapy dissipated after 10 days A subsequent report of 1-year outcomes found a durable treatment effect, but the HR for secondary stroke prevention was only significantly beneficial in the first 90 days.213 In addition, subgroup analyses found no benefit of clopidogrel plus aspirin in carriers of a CYP2C19 loss-of-function allele214 or those with a single acute infarction or no infarction compared with those with multiple acute infarctions,215 although these subgroup analyses were likely underpowered. The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke; N=4881) was conducted in North America, Europe, Australia, and New Zealand, with the majority (83%) enrolled in the United States (75% white, 20% Similar to CHANCE, the target enrollment population included minor stroke (NIHSS score 3) or high-risk TIA (ABCD2 score 4) within 12 hours of symptom onset. Patients were randomized to either clopidogrel plus aspirin (600-mg loading dose of clopidogrel followed by 75 mg/d from day 2 90) plus open-label aspirin (50 325 mg/d) versus aspirin alone (50 325 mg/d) for 90 days. The primary outcome was a composite of ischemic stroke, myocardial infarction (MI), or death resulting from an ischemic vascular event up to 90 days, with a secondary safety end point of major hemorrhage during the same time period.


The primary outcome was a composite of ischemic stroke, myocardial infarction (MI), or death resulting from an ischemic vascular event up to 90 days, with a secondary safety end point of major hemorrhage during the same time period. Compared with aspirin alone, aspirin plus clopidogrel resulted in fewer 0.4%; HR, 2.32 [95% CI, 1.10 4.87]; P=0.02). Overall, the beneficial effect of aspirin plus clopidogrel was driven by a reduction in ischemic stroke (HR, 0.72 [95% CI, 0.56 0.92]; P=0.01) and greatest in the first 30 days of treatment from symptom onset (HR, 0.73 [95% CI, 0.56 0.95]; P=0.02). However, the risk of major hemorrhage was greatest after the first 7 days of treatment (HR, 2.69 [95% CI, 1.05 6.86]; P=0.04). There was no significant added benefit of aspirin plus clopidogrel after 30 days of treatment. In addition, in a prespecified analysis of functional outcomes determined by 90- day mRS score 2 for new disability, there was no difference between groups (HR, 0.97 [95% CI, 0.82 1.14]; P=0.71). See Table XLVIII in online Data Supplement 1. The efficacy of the IV glycoprotein IIb/IIIa inhibitors tirofiban and eptifibatide in the treatment of AIS is not well established. IIb B-R Recommendation revised from 2013 AIS Guidelines. Prospective, randomized, open-label phase II trials of tirofiban217 have suggested safety for treatment in patients with AIS. Single-arm studies of eptifibatide as adjunctive therapy to IV alteplase support ongoing RCTs to establish safety and efficacy.173,174 Further trials are necessary to clarify the safety and efficacy of this intervention. See Tables XXXIX and XLVIII in online Data Supplement 1. Ticagrelor is not recommended over aspirin for treatment of patients with minor acute stroke. III: No Benefit B-R New recommendation.


Ticagrelor is not recommended over aspirin for treatment of patients with minor acute stroke. III: No Benefit B-R New recommendation. The recently completed SOCRATES trial (Acute Stroke or Transient Ischaemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was a randomized, double-blind, placebo-controlled trial of ticagrelor versus aspirin begun within 24 hours in patients with minor stroke (NIHSS score 5) or TIA (ABCD2 score 4). With a primary outcome of time to the composite end point of stroke, MI, or death up to 90 days, ticagrelor was not found to be superior to aspirin However, because there were no significant safety differences in the 2 groups, ticagrelor may be a reasonable alternative in stroke patients who have a contraindication to aspirin. See Table XLVIII in online Data Supplement 1. The administration of the IV glycoprotein IIb/IIIa inhibitor abciximab as medical treatment for AIS is potentially harmful and should not be performed. III: Harm B-R Recommendation revised from 2013 AIS Guidelines. A recent Cochrane review of IV glycoprotein IIb/IIIa receptor antagonists in the treatment of AIS found that these agents are associated with a significant risk of ICH without a measurable improvement in death or disability.220 The majority of trial data apply to abciximab, which was studied in the AbESTT trial (A Study of Effectiveness and Safety of Abciximab in Patients With Acute Ischemic Stroke). The phase III trial was terminated early because of an unfavorable risk-benefit analysis.221 See Table XLVIII in online Data Supplement 1. Aspirin is not recommended as a substitute for acute stroke treatment in patients who are otherwise eligible for IV alteplase or mechanical thrombectomy. III: Harm B-R Recommendation revised from 2013 AIS Guidelines.


Aspirin is not recommended as a substitute for acute stroke treatment in patients who are otherwise eligible for IV alteplase or mechanical thrombectomy. III: Harm B-R Recommendation revised from 2013 AIS Guidelines. Recommendation was modified to eliminate wording about acute interventions, which are broadly defined, and to specify that aspirin is a less effective substitute for the treatment of AIS in patients who are otherwise eligible for IV alteplase or mechanical thrombectomy. 3.9. Antiplatelet Treatment (Continued) COR LOE New, Revised, or Unchanged 3.10. Anticoagulants COR LOE New, Revised, or Unchanged The usefulness of urgent anticoagulation in patients with severe stenosis of an internal carotid artery ipsilateral to an ischemic stroke is not well established. IIb B-NR Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. The safety and usefulness of short-term anticoagulation for nonocclusive, extracranial intraluminal thrombus in the setting of AIS are not well established. IIb C-LD New recommendation. The optimal medical management of patients with AIS and radiologic evidence of nonocclusive, intraluminal thrombus (eg, cervical carotid, vertebrobasilar arteries) remains uncertain. Several small observational studies have suggested the safety of short-term IV heparin or LMWH in this setting,222,223 but further research is required to establish safety and efficacy. See Table XLIX in online Data Supplement 1. At present, the usefulness of argatroban, dabigatran, or other thrombin inhibitors for the treatment of patients with AIS is not well established. IIb B-R Recommendation revised from 2013 AIS Guidelines. Several observational studies have demonstrated the safety and feasibility of treating AIS with thrombin inhibitors as either a single or an adjunct therapy to alteplase.


Several observational studies have demonstrated the safety and feasibility of treating AIS with thrombin inhibitors as either a single or an adjunct therapy to alteplase. The oral direct thrombin inhibitor dabigatran was studied in 53 patients with TIA or minor stroke (NIHSS score 3) with no occurrences of sICH up to 30 days.224 ARTSS (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke)-1 was an open-label, pilot safety study of argatroban infusion plus IV alteplase in 65 patients with complete or partially occlusive thrombus diagnosed by transcranial In the ARTSS-2 phase II study, patients with AIS treated with alteplase (N=90) were randomized to receive placebo or argatroban (100- g/kg bolus), followed by infusion of either 1 (low dose) or 3 (high dose) g/kg per minute for 48 hours. Rates of sICH were similar among the control, low-dose, and high-dose arms: 3 of 29 (10%), 4 of 30 (13%), Further trials are necessary to clarify the safety and efficacy of this intervention. See Tables XLIX and L in online Data Supplement 1. The safety and usefulness of oral factor Xa inhibitors in the treatment of AIS are not well established. IIb C-LD New recommendation. Limited data exist on the use of factor Xa inhibitors (eg, rivaroxaban, apixaban, edoxaban) for treatment of patients with AIS.227 Several prospective observational studies and early-phase trials are ongoing (NCT02279940, NCT02042534, NCT02283294). Further clinical trials are needed. See Table LI in online Data Supplement 1. Urgent anticoagulation, with the goal of preventing early recurrent stroke, halting neurological worsening, or improving outcomes after AIS, is not recommended for treatment of patients with AIS. III: No Benefit A Recommendation and LOE unchanged from 2013 AIS Guidelines. COR amended to conform with ACC/AHA 2015 Recommendation Classification System.


COR amended to conform with ACC/AHA 2015 Recommendation Classification System. Further support for this unchanged recommendation from the 2013 AIS Guidelines is provided by 2 updated meta- analyses that confirm the lack of benefit of urgent anticoagulation.228,229 An additional study, not included in these meta-analyses, investigated the efficacy of LMWH compared with aspirin in preventing early neurological deterioration in an unblinded RCT. Although there was a statistically significant difference in early neurological deterioration at 10 days after admission (LMWH, 27 [3.95%] versus aspirin, 81 [11.82%]; P<0.001), there was no difference in 6-month See Table L in online Data Supplement 1. 3.11. Volume Expansion/Hemodilution, Vasodilators, and Hemodynamic Augmentation 3.11. Volume Expansion/Hemodilution, Vasodilators, and Hemodynamic Augmentation COR LOE New, Revised, or Unchanged Hemodilution by volume expansion is not recommended for treatment of patients with AIS. III: No Benefit A Recommendation and LOE unchanged from 2013 AIS Guidelines. COR amended to conform with ACC/AHA 2015 Recommendation Classification System. A recent Cochrane review of 4174 participants from multiple RCTs confirmed the previous guideline recommendation that hemodilution therapy, including varying methods of volume expansion with or without venesection, demonstrates no significant benefit in patients with AIS.231 See Table LII in online Data Supplement 1. The administration of high-dose albumin is not recommended for the treatment of patients with AIS. III: No Benefit A Recommendation revised from 2013 AIS Guidelines. The ALIAS (Albumin in Acute Ischemic Stroke) part II trial of high-dose albumin infusion versus placebo in patients with AIS was terminated early for futility.232 Combined analysis of the ALIAS parts I and II trials demonstrated no difference between groups in 90-day disability.233 See Table LII in online Data Supplement 1.


The ALIAS (Albumin in Acute Ischemic Stroke) part II trial of high-dose albumin infusion versus placebo in patients with AIS was terminated early for futility.232 Combined analysis of the ALIAS parts I and II trials demonstrated no difference between groups in 90-day disability.233 See Table LII in online Data Supplement 1. Powers et al 2019 Guidelines for Management of AIS e379 The administration of vasodilatory agents, such as pentoxifylline, is not recommended for treatment of patients with AIS. III: No Benefit A Recommendation and LOE unchanged from 2013 AIS Guidelines. COR amended to conform with ACC/AHA 2015 Recommendation Classification System. Devices to mechanically augment cerebral blood flow for the treatment of patients with AIS are not useful. III: No Benefit B-R New recommendation. Since the 2013 AHA/ASA Guideline, a safety and feasibility RCT of external counterpulsation in AIS has been External counterpulsation was safe and feasible to use in patients with AIS but was associated with unexpected effects on MCA flow velocity. At 30 days, there were no statistically significant differences in clinical end points between the 2 groups, but the study was not powered for this purpose. See Table LIII in online Data Supplement 1. 3.12. Neuroprotective Agents 3.12. Neuroprotective Agents COR LOE New, Revised, or Unchanged At present, pharmacological or nonpharmacological treatments with putative neuroprotective actions are not recommended. III: No Benefit A Recommendation reworded for clarity from 2013 AIS Guidelines. LOE unchanged. COR amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. There have been myriad attempts to establish the efficacy of pharmacological and nonpharmacological interventions with putative neuroprotective action in acute stroke that have failed when tested in human clinical trials.


There have been myriad attempts to establish the efficacy of pharmacological and nonpharmacological interventions with putative neuroprotective action in acute stroke that have failed when tested in human clinical trials. Since the 2013 AIS Guidelines, there have been several more trials testing putative neuroprotective agents that have been negative. The FAST-MAG trial (Field Administration of Stroke Therapy Magnesium) of prehospital magnesium infusion was the first acute stroke neuroprotection drug trial to enroll participants during ambulance transport, but no differences were seen between the intervention group and placebo control subjects.235 The ALIAS trials parts I and II failed to show the efficacy of IV albumin infusion in AIS.232,233 See Table LII in online Data Supplement 1. 3.13. Emergency Carotid Endarterectomy Carotid Angioplasty and Stenting Without Intracranial Clot 3.13. Emergency Carotid Endarterectomy/Carotid Angioplasty and Stenting Without Intracranial Clot COR LOE New, Revised, or Unchanged The usefulness of emergent or urgent carotid endarterectomy (CEA)/carotid angioplasty and stenting when clinical indicators or brain imaging suggests a small infarct core with large territory at risk (eg, penumbra), compromised by inadequate flow from a critical carotid stenosis or occlusion, or in the case of acute neurological deficit after CEA, in which acute thrombosis of the surgical site is suspected, is not well established. IIb B-NR Recommendation reworded for clarity from 2013 AIS Guidelines. COR unchanged. LOE amended to conform with the ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. In patients with unstable neurological status (eg, stroke-in-evolution), the efficacy of emergency or urgent CEA /carotid angioplasty and stenting is not well established. IIb B-NR Recommendation reworded for clarity from 2013 AIS Guidelines. COR unchanged. LOE amended to conform with the ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. 3.14.


See Table XCV in online Data Supplement 1 for original wording. 3.14. Other COR LOE New, Revised, or Unchanged Transcranial near-infrared laser therapy is not recommended for the treatment of AIS. III: No Benefit B-R Recommendation revised from 2013 AIS Guidelines. Previous data suggested that transcranial near-infrared laser therapy for stroke held promise as a therapeutic intervention through data published in NEST (Neurothera Effectiveness and Safety Trial)-1 and NEST-2.236 238 Such basic science and preclinical data culminated in the NEST-3 trial, which was a prospective RCT. This trial investigated the use of transcranial laser therapy for the treatment of ischemic stroke between 4.5 and 24 hours of stroke onset in patients with moderate stroke (NIHSS score 7 17) who did not receive IV alteplase.239 This study was terminated because of futility after analysis of the first 566 patients found no benefit of transcranial laser therapy over sham treatment. There is currently no evidence that transcranial laser therapy is beneficial in the treatment of ischemic stroke. See Table LIV in online Data Supplement 1. 3.11. Volume Expansion/Hemodilution, Vasodilators, and Hemodynamic Augmentation (Continued) COR LOE New, Revised, or Unchanged 4. In-Hospital Management of AIS: General Supportive Care 4.1. Stroke Units 4.1. Stroke Units COR LOE New, Revised, or Unchanged The use of comprehensive specialized stroke care (stroke units) that incorporates rehabilitation is recommended. I A Recommendation unchanged from 2013 AIS Guidelines. The use of standardized stroke care order sets is recommended to improve general management. I B-NR Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. 4.2 Head Positioning 4.2 Head Positioning COR LOE New, Revised, or Unchanged The benefit of flat-head positioning early after hospitalization for stroke is uncertain. IIb B-R New recommendation.


4.2 Head Positioning 4.2 Head Positioning COR LOE New, Revised, or Unchanged The benefit of flat-head positioning early after hospitalization for stroke is uncertain. IIb B-R New recommendation. Only 1 sizable trial has evaluated the effect on functional outcomes of flat versus elevated head position after a stroke. HeadPoST (Head Positioning in Acute Stroke Trial) was a large international, cluster-randomized, crossover open- label trial that enrolled any patient hospitalized for stroke (including ICHs) admitted to the hospital to flat-head (0 ) or elevated head ( 30 ) maintained for 24 hours after randomization.240 Distribution of mRS scores at 90 days did not differ between the groups (OR, 1.01 [95% CI, 0.92 1.10]; P=0.84). Patients in the flat-head position group were less often able to maintain the assigned head position for 24 hours, but rates of pneumonia did not differ between the 2 groups. However, this pragmatic trial has been criticized because of various limitations.241 HeadPoST enrolled predominantly patients with minor strokes (median NIHSS score 4) who would be less likely to benefit from increased perfusion compared with patients with more severe strokes and large artery occlusions. In addition, the initiation of the intervention was very delayed (median, 14 hours), potentially missing the window in which head positioning could have made a difference. Several small studies have shown that the lying-flat position may improve cerebral perfusion in patients with AIS caused by a large artery occlusion when the intervention is initiated early after stroke onset.241,242 Thus, there is a rationale for further research focused on this specific cohort of patients. See Table LV in online Data Supplement 1. 4.3. Supplemental Oxygen Note: Recommendations in this section are repeated from Section 3.1 because they apply to in-hospital management as well. 4.3.


Supplemental Oxygen Note: Recommendations in this section are repeated from Section 3.1 because they apply to in-hospital management as well. 4.3. Supplemental Oxygen COR LOE New, Revised, or Unchanged Airway support and ventilatory assistance are recommended for the treatment of patients with acute stroke who have decreased consciousness or who have bulbar dysfunction that causes compromise of the airway. I C-EO Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. Supplemental oxygen should be provided to maintain oxygen saturation >94%. I C-LD Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. Supplemental oxygen is not recommended in nonhypoxic patients hospitalized with AIS. III: No Benefit B-R Recommendation reworded for clarity from 2013 AIS Guidelines. COR and LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. Additional support for this unchanged recommendation from the 2013 AIS Guidelines is provided by an RCT of 8003 participants randomized within 24 hours of admission. There was no benefit on functional outcome at 90 days of oxygen by nasal cannula at 2 L/min (baseline O2 continuously for 72 hours or nocturnally for 3 nights.112 See Table XXVII in online Data Supplement 1. Powers et al 2019 Guidelines for Management of AIS e381 4.4. Blood Pressure Note: Recommendation 1 in this section is repeated from Section 3.2 because it applies to in-hospital management as well. 4.4. Blood Pressure COR LOE New, Revised, or Unchanged Hypotension and hypovolemia should be corrected to maintain systemic perfusion levels necessary to support organ function. I C-EO New recommendation. The BP level that should be maintained in patients with AIS to ensure that the best outcome is not known.


The BP level that should be maintained in patients with AIS to ensure that the best outcome is not known. Some observational studies show an association between worse outcomes and lower BPs, whereas others do not.116 123 No studies address the treatment of low BP in patients with stroke. In a systematic analysis of 12 studies comparing colloids with crystalloids, the odds of death or dependence were similar. Clinically important benefits or harms could not be excluded. There are no data to guide volume and duration of parenteral fluid delivery.124 No studies have compared different isotonic fluids. See Table XXIX in online Data Supplement 1. In patients with AIS, early treatment of hypertension is indicated when required by comorbid conditions (eg, concomitant acute coronary event, acute heart failure, aortic dissection, postfibrinolysis sICH, or preeclampsia/ eclampsia). I C-EO New recommendation. Patients with AIS can present with severe acute comorbidities that demand emergency BP reduction to prevent serious complications. However, it is important to keep in mind that excessive BP lowering can sometimes worsen cerebral Ideal management in these situations should be individualized, but in general, initial BP reduction by 15% is a reasonable goal. There are no data to show that one strategy to lower BP is better than another after AIS. The medications and doses in Table 5 are all reasonable options. In patients with BP 220/120 mmHg who did not receive IV alteplase or mechanical thrombectomy and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating treatment of hypertension within the first 48 to 72 hours is uncertain. It might be reasonable to lower BP by 15% during the first 24 hours after onset of stroke. IIb C-EO New recommendation.


It might be reasonable to lower BP by 15% during the first 24 hours after onset of stroke. IIb C-EO New recommendation. Patients with severe hypertension (most commonly >220/120 mmHg) were excluded from clinical trials evaluating BP lowering after AIS.244 249 Rapid BP reduction has traditionally been advised for these cases, but the benefit of such treatment in the absence of comorbid conditions that may be acutely exacerbated by severe hypertension has not been formally studied. Ideal management in these situations should be individualized, but in general, initial BP reduction by 15% is a reasonable goal. Excessive drop in BP could result in complications such as stroke progression (by compromising cerebral perfusion in penumbral tissue) and acute kidney injury (from renal hypoperfusion). There are no data to show that one strategy to lower BP is better than another after AIS. The medications and doses in Table 5 are all reasonable options. See Table LVI in online Data Supplement 1. 4. In patients with BP <220/120 mmHg who did not receive IV alteplase or mechanical thrombectomy and do not have a comorbid condition requiring urgent antihypertensive treatment, initiating or reinitiating treatment of hypertension within the first 48 to 72 hours after an AIS is not effective to prevent death or dependency. III: No Benefit A Recommendation revised from 2013 AIS Guidelines. Multiple RCTs and meta-analyses of these trials244 258 have consistently shown that initiating or reinitiating antihypertensive therapy within the first 48 to 72 hours after an AIS is safe, but this strategy is not associated with improved mortality or functional outcomes. However, none of these trials were designed to study BP reduction within the first 6 hours after stroke, and all excluded patients with extreme hypertension or coexistent indications for rapid BP reduction.


However, none of these trials were designed to study BP reduction within the first 6 hours after stroke, and all excluded patients with extreme hypertension or coexistent indications for rapid BP reduction. See Table LVI in online Data Supplement 1. Note: Recommendations in this section are repeated from Section 3.3 because they apply to in-hospital management as well. 4.5. Temperature COR LOE New, Revised, or Unchanged Sources of hyperthermia (temperature >38 C) should be identified and treated. Antipyretic medications should be administered to lower temperature in hyperthermic patients with stroke. I C-LD Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. Additional support for this recommendation unchanged from the 2013 AIS Guidelines is provided by a large retrospective cohort study conducted from 2005 to 2013 of patients admitted to intensive care units in Australia, New Zealand, and the United Kingdom. Peak temperature in the first 24 hours <37 C and >39 C was associated with an increased risk of in-hospital death compared with normothermia in 9366 patients with AIS.133 See Tables XXXI and XXXII in online Data Supplement 1. In patients with AIS, the benefit of treatment with induced hypothermia is uncertain. IIb B-R Recommendation revised from 2013 AIS Guidelines. To date, studies of hypothermia in AIS show no benefit in functional outcome and suggest that induction of hypothermia increases the risk of infection, including pneumonia.134 137 These studies use a variety of methods to induce hypothermia and are small/underpowered, meaning that a benefit for hypothermia in AIS cannot be definitively excluded. A large phase III trial of hypothermia in AIS is ongoing. See Tables XXXIII and XXXIV in online Data Supplement 1. Note: Recommendations in this section are repeated from Section 3.4 because they apply to in-hospital management as well.


Note: Recommendations in this section are repeated from Section 3.4 because they apply to in-hospital management as well. 4.6. Glucose COR LOE New, Revised, or Unchanged Hypoglycemia (blood glucose <60 mg/dL) should be treated in patients with AIS. I C-LD Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. Evidence indicates that persistent in-hospital hyperglycemia during the first 24 hours after AIS is associated with worse outcomes than normoglycemia, and thus, it is reasonable to treat hyperglycemia to achieve blood glucose levels in a range of 140 to 180 mg/dL and to closely monitor to prevent hypoglycemia. IIa C-LD Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. 4.7. Dysphagia COR LOE New, Revised, or Unchanged Dysphagia screening before the patient begins eating, drinking, or receiving oral medications is effective to identify patients at increased risk for aspiration. I C-LD New recommendation. Dysphagia, a common (37% 78%) complication of acute stroke, is a risk factor for aspiration pneumonia and is associated with higher mortality and worse patient outcomes. The Evidence Review Committee completed a systematic review to determine whether dysphagia screening, compared with no screening or usual care, decreased outcomes of pneumonia, death, or dependency.3,259 261 There were insufficient data to determine whether implementation of a dysphagia screening protocol reduces the risk of death or dependency. However, insufficient evidence does not mean that dysphagia screening is ineffective. Joundi et al262 determined that patients who failed dysphagia screening were older, had a higher rate of multiple comorbidities (including prior stroke and dementia), more often came from a long-term care facility, more often presented with weakness and speech deficits, had a lower level of consciousness, and had a higher stroke severity.


Joundi et al262 determined that patients who failed dysphagia screening were older, had a higher rate of multiple comorbidities (including prior stroke and dementia), more often came from a long-term care facility, more often presented with weakness and speech deficits, had a lower level of consciousness, and had a higher stroke severity. Patients who failed dysphagia screening were more likely to develop pneumonia (13.1% versus 1.9%), to have more severe disability (52.4% versus 18.0%), and to be discharged to a long-term care institution (14.0% versus 4.3%). Early dysphagia screening can be effective to identify patients at higher risk for aspiration, which is associated with greater risk of pneumonia, even if dysphagia screening was not associated with reduced rates of pneumonia or improvements in death or disability when tested See Tables LVII and LVIII in online Data Supplement 1. An endoscopic evaluation is reasonable for those patients suspected of aspiration to verify the presence/absence of aspiration and to determine the physiological reasons for the dysphagia to guide the treatment plan. IIa B-NR Recommendation wording modified from 2016 Rehab Guidelines to match COR IIa stratifications. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. It is reasonable for dysphagia screening to be performed by a speech- language pathologist or other trained healthcare provider. IIa C-LD Recommendation reworded for clarity from 2016 Rehab Guidelines. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. It is not well established which instrument to choose for evaluation of swallowing with sensory testing, but the choice may be based on instrument availability or other considerations (ie, fiberoptic endoscopic evaluation of swallowing, videofluoroscopy, fiberoptic endoscopic evaluation with sensory testing). IIb C-LD Recommendation reworded for clarity from 2016 Rehab Guidelines. COR unchanged.


IIb C-LD Recommendation reworded for clarity from 2016 Rehab Guidelines. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. Powers et al 2019 Guidelines for Management of AIS e383 Implementing oral hygiene protocols to reduce the risk of pneumonia after stroke may be reasonable. IIb B-NR New recommendation. Limited studies suggest that intensive oral hygiene protocols might reduce the risk of aspiration pneumonia. In patients with acute stroke, S rensen et al263 showed that intervention with standardized dysphagia screening and diet and standardized oral hygiene with antibacterial mouth rinse with chlorhexidine reduced pneumonia (7% versus 28%) compared with a historical control group in which patients were unsystematically screened for dysphagia within 24 hours and received unsystematic and arbitrary oral hygiene without chlorhexidine. In this experimental design, the efficacy of the standardized oral hygiene portion in the intervention group could not be separated from the standardized dysphagia screening and diet. Furthermore, because of the historic nature of the control group, it is possible that other changes in care that could have occurred between the historical control subjects and the intervention group might have affected the risk for development of pneumonia. A Cochrane review that included 3 studies found that oral care and decontamination gel versus oral care and placebo gel reduced the incidence of pneumonia in the intervention group (P=0.03).264 Wagner et al265 conducted a cohort study comparing rates of pneumonia in hospitalized stroke patients before and after implementation of systematic oral hygiene care. The unadjusted incidence of hospital-acquired pneumonia was lower in the group assigned to oral hygiene care compared with control subjects (14% versus 10.33%; P=0.022), with an unadjusted OR of 0.68 (95% CI, 0.48 0.95; P=0.022).


The unadjusted incidence of hospital-acquired pneumonia was lower in the group assigned to oral hygiene care compared with control subjects (14% versus 10.33%; P=0.022), with an unadjusted OR of 0.68 (95% CI, 0.48 0.95; P=0.022). After adjustment for confounders, the OR of hospital-acquired pneumonia in the intervention group remained significantly lower at 0.71 (95% CI, 0.51 0.98; P=0.041). See Tables LIX and LX in online Data Supplement 1. 4.8. Nutrition COR LOE New, Revised, or Unchanged Enteral diet should be started within 7 days of admission after an acute stroke. I B-R New recommendation. For patients with dysphagia, it is reasonable to initially use nasogastric tubes for feeding in the early phase of stroke (starting within the first 7 days) and to place percutaneous gastrostomy tubes in patients with longer anticipated persistent inability to swallow safely (>2 3 weeks). IIa C-EO New recommendation. The FOOD RCTs (Feed or Ordinary Diet; phases I III), completed in 131 hospitals in 18 countries,266 showed that supplemented diet was associated with an absolute reduction in risk of death of 0.7% and that early tube feeding (within 7 days of admission) was associated with an absolute reduction in risk of death of 5.8% and a reduction in death or poor outcomes of 1.2%. When nasogastric feeding and percutaneous endoscopic gastrostomy feeding were compared, percutaneous endoscopic gastrostomy feeding was associated with an increase in absolute risk of death of 1.0% and an increased risk of death or poor outcomes of 7.8%.


When nasogastric feeding and percutaneous endoscopic gastrostomy feeding were compared, percutaneous endoscopic gastrostomy feeding was associated with an increase in absolute risk of death of 1.0% and an increased risk of death or poor outcomes of 7.8%. The conclusion was that stroke patients should be started on enteral diet within the first 7 days of admission.266 In 2012, a Cochrane review analyzed 33 RCTs involving 6779 patients to assess the intervention for dysphagia treatment, feeding strategies and timing (early [within 7 days] versus later), fluid supplementation, and the effects of nutritional supplementation on acute and subacute The conclusion was that, although data remained insufficient to offer definitive answers, available information suggested that percutaneous endoscopic gastrostomy feeding and nasogastric tube feeding do not differ in terms of case fatality, death, or dependency, but percutaneous endoscopic gastrostomy is associated with fewer treatment failures (P=0.007), less gastrointestinal bleeding (P=0.007), and higher food delivery (P<0.00001). See Table LXI in online Data Supplement 1. Nutritional supplements are reasonable to consider for patients who are malnourished or at risk of malnourishment. IIa B-R Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. 4.9. Deep Vein Thrombosis Prophylaxis 4.9. Deep Vein Thrombosis Prophylaxis COR LOE New, Revised, or Unchanged In immobile stroke patients without contraindications, intermittent pneumatic compression (IPC) in addition to routine care (aspirin and hydration) is recommended over routine care to reduce the risk of deep vein thrombosis (DVT). I B-R Recommendation revised from 2016 Rehab Guidelines. CLOTS (Clots in Legs or stockings After Stroke) 3 was a multicenter trial enrolling 2867 patients in 94 centers in the United Kingdom and comparing the use of IPC with routine care and no IPC with routine care in immobile stroke patients for venous thromboembolism prophylaxis.


CLOTS (Clots in Legs or stockings After Stroke) 3 was a multicenter trial enrolling 2867 patients in 94 centers in the United Kingdom and comparing the use of IPC with routine care and no IPC with routine care in immobile stroke patients for venous thromboembolism prophylaxis. Eligible patients were enrolled within 3 days of the acute stroke and could not mobilize to the toilet without the help of another person. Routine care was defined as the use of aspirin for nonhemorrhagic stroke, hydration, and possible compression stockings. A total of 31% of the patients received prophylactic or full-dose heparin or LMWH, but these patients were evenly distributed between both groups. After the exclusion of 323 patients who died before any primary outcome and 41 who had no screening, the primary outcome of DVT occurred in 122 of 1267 participants with IPC (9.6%) compared with 174 of 1245 participants without IPC (14.0%), giving an adjusted OR of 0.65 (95% CI, 0.51 0.84; P=0.001). Among patients treated with IPC, there was a statistically significant improvement in survival to 6 months (HR, 0.86 [95% CI, 0.73 0.99]; P=0.042) but no improvement in disability. Skin breaks were more common in the IPC group (3.1% versus 1.4%; P=0.002). Contraindications to IPC include leg conditions such as dermatitis, gangrene, severe edema, venous stasis, severe peripheral vascular disease, postoperative vein ligation, or grafting, as well as existing swelling or other signs of an existing DVT.268 A meta-analysis including this trial and 2 smaller trials confirmed these results.269 See Table LXII in online Data Supplement 1. 4.7. Dysphagia (Continued) COR LOE New, Revised, or Unchanged The benefit of prophylactic-dose subcutaneous heparin (unfractionated heparin [UFH] or LMWH) in patients with AIS is not well established. IIb A New recommendation.


Dysphagia (Continued) COR LOE New, Revised, or Unchanged The benefit of prophylactic-dose subcutaneous heparin (unfractionated heparin [UFH] or LMWH) in patients with AIS is not well established. IIb A New recommendation. The most recent and comprehensive meta-analysis of pharmacological interventions for venous thromboembolism prophylaxis in AIS included 1 very large trial (N=14578), 4 small trials of UFH, 8 small trials of LMWHs or heparinoids, and 1 trial of a heparinoid.269 Prophylactic anticoagulants were not associated with any significant effect on mortality or functional status at final follow-up. There were statistically significant reductions in symptomatic pulmonary embolisms (OR, 0.69 [95% CI, 0.49 0.98]) and in DVTs (OR, 0.21 [95% CI, 0.15 0.29]), most of which were asymptomatic. There were statistically significant increases in symptomatic intracranial hemorrhage (OR, 1.68 [95% CI, 1.11 2.55]) and symptomatic extracranial hemorrhages (OR, 1.65 [95% CI, 1.0 2.75]).269 There may be a subgroup of patients in whom the benefits of reducing the risk of venous thromboembolism are high enough to offset the increased risks of intracranial and extracranial bleeding; however, no prediction tool to identify such a subgroup has See Table LXII in online Data Supplement 1. When prophylactic anticoagulation is used, the benefit of prophylactic-dose LMWH over prophylactic-dose UFH is uncertain. IIb B-R New recommendation. The most recent and comprehensive meta-analysis comparing LMWH or heparinoid with UFH for venous thromboembolism prophylaxis in AIS included 1 large trial (N=1762) and 2 smaller trials comparing LMWH with UFH and 4 small trials comparing heparinoids with UFH.


The most recent and comprehensive meta-analysis comparing LMWH or heparinoid with UFH for venous thromboembolism prophylaxis in AIS included 1 large trial (N=1762) and 2 smaller trials comparing LMWH with UFH and 4 small trials comparing heparinoids with UFH. There were no significant effects on death or disability for LMWH/heparinoids compared with UFH.269 The use of LMWH/heparinoid was associated with a statistically significant reduction in DVTs (OR, 0.55 [95% CI, 0.44 0.70]), which were mostly asymptomatic, at the expense of a greater risk of major extracranial hemorrhages (OR, 3.79 [95% CI, 1.30 11.03]). LMWH can be administered once a day and thus is more convenient for nurses and comfortable for patients. Higher cost and increased bleeding risk in elderly patients with renal impairment are disadvantages of LMWH that should be kept in mind. See Table LXII in online Data Supplement 1. 4. In ischemic stroke, elastic compression stockings should not be used. III: Harm B-R Recommendation wording modified from 2016 Rehab Guidelines to match COR III stratifications. COR and LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. 4.10. Depression Screening 4.10. Depression Screening COR LOE New, Revised, or Unchanged Administration of a structured depression inventory is recommended to routinely screen for poststroke depression. I B-NR Recommendation revised from 2016 Rehab Guidelines. A meta-analysis of studies assessing poststroke depression screening tools (24 studies, N=2907) found several inventories with high sensitivity for detecting poststroke depression.270 Two of these studies evaluated patients in the acute phase 2 weeks after onset and found that depression screening tools showed good accuracy compared with the reference standard diagnosis by the American Psychiatric Association Diagnostic and Statistical Manual of However, further studies are needed to determine the optimal timing, setting, and follow-up for See Tables LXIII and LXIV in online Data Supplement 1.


A meta-analysis of studies assessing poststroke depression screening tools (24 studies, N=2907) found several inventories with high sensitivity for detecting poststroke depression.270 Two of these studies evaluated patients in the acute phase 2 weeks after onset and found that depression screening tools showed good accuracy compared with the reference standard diagnosis by the American Psychiatric Association Diagnostic and Statistical Manual of However, further studies are needed to determine the optimal timing, setting, and follow-up for See Tables LXIII and LXIV in online Data Supplement 1. Patients diagnosed with poststroke depression should be treated with antidepressants in the absence of contraindications and closely monitored to verify effectiveness. I B-R Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. Clinical trials of antidepressants in individuals with poststroke depression have shown a beneficial effect on depression remission and response, but trials were limited by small samples, variable criteria for poststroke depression, and vague definitions for remission and response.16 Several trials have indicated a benefit of psychosocial therapies for treatment.16 In an RCT, participants who underwent screening in the early subacute period 1 to 2 months after stroke followed by treatment with counseling antidepressant medication showed significantly lower 12-week depression scores than those who received usual care.273 See Tables LXV and LXVI in online Data Supplement 1. 4.9. Deep Vein Thrombosis Prophylaxis (Continued) COR LOE New, Revised, or Unchanged Powers et al 2019 Guidelines for Management of AIS e385 4.11. Other COR LOE New, Revised, or Unchanged During hospitalization and inpatient rehabilitation, regular skin assessments are recommended with objective scales of risk such as the Braden scale. I C-LD Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System.


LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. It is recommended to minimize or eliminate skin friction, to minimize skin pressure, to provide appropriate support surfaces, to avoid excessive moisture, and to maintain adequate nutrition and hydration to prevent skin breakdown. Regular turning, good skin hygiene, and use of specialized mattresses, wheelchair cushions, and seating are recommended until mobility returns. I C-LD Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. It is reasonable for patients and families with stroke to be directed to palliative care resources as appropriate. IIa C-EO New recommendation. It is reasonable for healthcare providers to ascertain and include patient-centered preferences in decision-making, especially during prognosis formation and considering interventions or limitations in care. Healthcare providers should ascertain and include patient-centered preferences in decision-making, especially during prognosis formation and considering interventions or limitations in care. See 2014 Palliative Care for additional information.9 4. Routine use of prophylactic antibiotics has not been shown to be beneficial. III: No Benefit A Recommendation revised from 2013 AIS Guidelines. Two large RCTs demonstrated no effect of preventive antimicrobial therapy on functional outcome.


Two large RCTs demonstrated no effect of preventive antimicrobial therapy on functional outcome. PASS (Preventive Antibiotics in Stroke Study) showed no difference in the primary end point of distribution of functional outcome scores on the mRS score at 3 months (adjusted common OR, 0.95 [95% CI, 0.82 1.09]; P=0.46) despite an overall reduction in the incidence of infection (OR, 0.57 [95% CI, 0.38 0.85]; P=0.005), including reducing the number of urinary tract infections (OR, 0.34 [95% CI, 0.26 0.46]; P<0.001), but no significant decrease in the rate of poststroke pneumonia In STROKE-INF (Antibiotics to Prevent Infection in Stroke), prophylactic antibiotics did not affect the incidence of the primary end point of poststroke pneumonia (adjusted OR,1.21 [95% CI, 0.71 2.08]; P=0.489) or the secondary end point of mRS score of 0 to 2 at 90 days (adjusted OR, 0.87 [95% CI, 0.6 Three meta-analyses including these trials and other smaller RCTs all demonstrated a reduction in infection but no change in functional outcome.276 278 See Table LXVII in online Data Supplement 1. Routine placement of indwelling bladder catheters should not be performed because of the associated risk of catheter-associated urinary tract infections. III: Harm C-LD Recommendation wording modified from 2013 AIS Guidelines to match COR III stratifications. COR and LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. 4.12. Rehabilitation COR LOE New, Revised, or Unchanged It is recommended that early rehabilitation for hospitalized stroke patients be provided in environments with organized, interprofessional stroke care. I A Recommendation unchanged from 2016 Rehab Guidelines. It is recommended that stroke survivors receive rehabilitation at an intensity commensurate with anticipated benefit and tolerance. I B-NR Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System.


LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. It is recommended that all individuals with stroke be provided a formal assessment of their activities of daily living and instrumental activities of daily living, communication abilities, and functional mobility before discharge from acute care hospitalization and the findings be incorporated into the care transition and the discharge planning process. I B-NR Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. A functional assessment by a clinician with expertise in rehabilitation is recommended for patients with an acute stroke with residual functional deficits. I C-LD Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. The effectiveness of fluoxetine or other selective serotonin reuptake inhibitors to enhance motor recovery is not well established. IIb C-LD Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE revised from 2016 Rehab Guidelines. High-dose, very early mobilization within 24 hours of stroke onset should not be performed because it can reduce the odds of a favorable outcome at 3 months. III: Harm B-R Recommendation wording modified from 2016 Rehab Guidelines to match COR III stratifications. LOE revised. COR amended to conform with ACC/AHA 2015 Recommendation Classification System. The AVERT RCT (A Very Early Rehabilitation Trial) compared high-dose, very early mobilization with standard-of-care High-dose mobilization protocol interventions included the following: Mobilization was begun within 24 hours of stroke onset, whereas usual care typically was 24 hours after the onset of stroke; there was a focus on sitting, standing, and walking activity; and there were at least 3 additional out-of-bed sessions compared with usual care. Favorable outcome at 3 months after stroke was defined as an mRS score of 0 to 2.


Favorable outcome at 3 months after stroke was defined as an mRS score of 0 to 2. A total of 2104 patients were randomly assigned (1:1). The results of this RCT showed that patients in the high-dose, very early mobilization group had less favorable outcomes (46% versus 50%) than those in the usual care group: 8% versus 7% of patients died in the very early mobilization group, and 19% versus 20% had a nonfatal serious adverse event with high-dose, very early mobilization. See Table LXVIII in online Data Supplement 1. 5. In-Hospital Management of AIS: Treatment of Acute Complications 5.1. Brain Swelling 5.1.1. General Recommendations COR LOE New, Revised, or Unchanged Patients with large territorial cerebral and cerebellar infarctions are at high risk for developing brain swelling and herniation. Discussion of care options and possible outcomes should take place quickly with patients (if possible) and family or next of kin. Medical professionals and caregivers should ascertain and include patient-centered preferences in shared decision- making, especially during prognosis formation and when considering interventions or limitations in care. I C-EO New recommendation. Brain swelling can cause serious and even life-threatening complications in patients with large territorial cerebral and cerebellar infarctions. Although less severe swelling can be managed medically, surgical treatment may be the only effective option for very severe cases; in such instances, timely decompressive surgery has been shown to reduce Nevertheless, there is evidence that persistent morbidity is common, and individual preexisting decisions about end-of-life and degree of treatment performed in the face of severe neurological injury must be considered. See Tables LXIX and LXX in online Data Supplement 1. Measures to lessen the risk of swelling and close monitoring of the patient for signs of neurological worsening during the first days after stroke are recommended.


Measures to lessen the risk of swelling and close monitoring of the patient for signs of neurological worsening during the first days after stroke are recommended. Early transfer of patients at risk for malignant brain swelling to an institution with appropriate neurosurgical expertise should be considered. I C-LD Recommendation reworded for brevity and consistency from 2013 AIS Guidelines. LOE revised. See Table XCV in online Data Supplement 1 for original wording. 5.1.2. Medical Management COR LOE New, Revised, or Unchanged Use of osmotic therapy for patients with clinical deterioration from brain swelling associated with cerebral infarction is reasonable. IIa C-LD Recommendation reworded for clarity from 2014 Brain Swelling. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. Use of brief moderate hyperventilation (Pco2 target, 30 34 mmHg) is a reasonable treatment for patients with acute severe neurological decline from brain swelling as a bridge to more definitive therapy. IIa C-LD New recommendation. A single nonrandomized study of 3 days of sustained hyperventilation in AIS designed primarily to investigate physiological changes showed no difference in mortality.281 Data on the use of hyperventilation for the management of increased intracranial pressure from patients with traumatic brain injury show a rapid reduction in intracranial pressure with return toward baseline over the next few hours.282 284 The only RCT of sustained hyperventilation in traumatic brain injury demonstrated that prophylactic hyperventilation for 5 days was associated with worse outcomes.285 See Tables LXXI and LXXII in online Data Supplement 1. Hypothermia or barbiturates in the setting of ischemic cerebral or cerebellar swelling are not recommended. III: No Benefit B-R Recommendation and LOE revised from 2014 Brain Swelling. COR amended to conform with ACC/AHA 2015 Recommendation Classification System.


COR amended to conform with ACC/AHA 2015 Recommendation Classification System. The data on the use of hypothermia and barbiturates for the management of AIS continue to be limited. Such data include only studies with small numbers of patients and unclear timing of intervention with respect to stroke onset. Hypothermia use has recently been shown to have no impact on stroke outcomes in a meta-analysis of 6 RCTs.286 Further trials are necessary to clarify the safety and efficacy of this intervention. See Tables LXIX and LXX in online Data Supplement 1. 4.12. Rehabilitation (Continued) COR LOE New, Revised, or Unchanged Powers et al 2019 Guidelines for Management of AIS e387 Because of a lack of evidence of efficacy and the potential to increase the risk of infectious complications, corticosteroids (in conventional or large doses) should not be administered for the treatment of brain swelling complicating ischemic stroke. III: Harm A Recommendation wording modified from 2013 AIS Guidelines to match COR III stratifications. LOE unchanged. COR amended to conform with ACC/AHA 2015 Recommendation Classification System. 5.1.3. Surgical Management-Supratentorial Infarction COR LOE New, Revised, or Unchanged Although the optimal trigger for decompressive craniectomy is unknown, it is reasonable to use a decrease in level of consciousness attributed to brain swelling as selection criteria. IIa A Recommendation, COR, and LOE unchanged from 2014 Brain Swelling. In patients 60 years of age who deteriorate neurologically within 48 hours from brain swelling associated with unilateral MCA infarctions despite medical therapy, decompressive craniectomy with dural expansion is reasonable. IIa A Recommendation revised from 2014 Brain Swelling.


In patients 60 years of age who deteriorate neurologically within 48 hours from brain swelling associated with unilateral MCA infarctions despite medical therapy, decompressive craniectomy with dural expansion is reasonable. IIa A Recommendation revised from 2014 Brain Swelling. The pooled results of RCTs demonstrated significant reduction in mortality when decompressive craniectomy was performed within 48 hours of malignant MCA infarction in patients <60 years of age, with an absolute risk reduction in These findings were noted despite differences in the clinical trials in terms of inclusion and exclusion criteria, percent of MCA territory involved, and surgical timing.287,288 At 12 months, moderate disability (ability to walk) or better (mRS score 2 or 3) was achieved in 43% (22 of 51) of the total surgical group and 55% (22 of 40) of survivors compared with 21% (9 of 42; P=0.045) of the total nonsurgical group and 75% (9 of 12; P=0.318) of the nonsurgical survivors. At 12 months, independence (mRS score 2) was achieved in 14% (7 of 51) of the total surgical group and 18% (7 of 40) of survivors compared with 2% (1 of 42) of the total nonsurgical group and 8% (1 of 12) of the nonsurgical survivors.280,287 290 See Tables LXIX and LXX in online Data Supplement 1. In patients >60 years of age who deteriorate neurologically within 48 hours from brain swelling associated with unilateral MCA infarctions despite medical therapy, decompressive craniectomy with dural expansion may be considered.


In patients >60 years of age who deteriorate neurologically within 48 hours from brain swelling associated with unilateral MCA infarctions despite medical therapy, decompressive craniectomy with dural expansion may be considered. IIb B-R Recommendation revised from 2014 Brain Swelling There is evidence that patients >60 years of age can have a reduction in mortality of 50% (76% in the nonsurgical group versus 42% in the surgical group in DESTINY [Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery] II) when decompressive craniectomy for malignant MCA infarction is performed within 48 hours of stroke onset.287,288,291 295 However, functional outcomes in elderly patients seem to be worse than those in patients <60 years of age. At 12 months, moderate disability (able to walk; mRS score 3) was achieved in 6% (3 of 47) of the total surgical group and 11% (3 of 27) of survivors compared with 5% (3 of 22) of the total nonsurgical group and 20% (3 of 15) of the nonsurgical survivors. At 12 months, independence (mRS score 2) was not achieved by any survivors in either group. See Tables LXIX and LXX in online Data Supplement 1. 5.1.4. Surgical Management-Cerebellar Infarction COR LOE New, Revised, or Unchanged Ventriculostomy is recommended in the treatment of obstructive hydrocephalus after cerebellar infarction. Concomitant or subsequent decompressive craniectomy may or may not be necessary on the basis of factors such as the size of the infarction, neurological condition, degree of brainstem compression, and effectiveness of medical management. I C-LD Recommendation revised from 2014 Brain Swelling.


Concomitant or subsequent decompressive craniectomy may or may not be necessary on the basis of factors such as the size of the infarction, neurological condition, degree of brainstem compression, and effectiveness of medical management. I C-LD Recommendation revised from 2014 Brain Swelling. Ventriculostomy is a well-recognized effective treatment for the management of acute obstructive hydrocephalus and is often effective in isolation in relieving symptoms, even among patients with acute cerebellar infarction.289,296 Thus, in patients who develop symptoms of obstructive hydrocephalus from cerebellar infarction, emergency ventriculostomy is a reasonable first step in the surgical management paradigm. If cerebrospinal fluid diversion by ventriculostomy fails to improve neurological function, decompressive suboccipital craniectomy should be performed.289,296,297 Although a risk of upward herniation exists with ventriculostomy alone, it can be minimized with conservative cerebrospinal fluid drainage or subsequent decompression if the cerebellar infarction causes significant swelling and mass effect.289,296 See Table LXIX in online Data Supplement 1. Decompressive suboccipital craniectomy with dural expansion should be performed in patients with cerebellar infarction causing neurological deterioration from brainstem compression despite maximal medical therapy. When deemed safe and indicated, obstructive hydrocephalus should be treated concurrently with ventriculostomy. I B-NR Recommendation revised from 2014 Brain Swelling. The data support decompressive cerebellar craniectomy for the management of acute ischemic cerebellar stroke with mass effect.289,296,297 This surgery is indicated as a therapeutic intervention in cases of neurological deterioration caused by swelling as a result of cerebellar infarction that cannot be otherwise managed with medical therapy or ventriculostomy in the setting of obstructive hydrocephalus.289,296 See Table LXIX in online Data Supplement 1. 5.1.2. Medical Management (Continued) COR LOE New, Revised, or Unchanged When considering decompressive suboccipital craniectomy for cerebellar infarction, it may be reasonable to inform family members that the outcome after cerebellar infarct can be good after the surgery.


Medical Management (Continued) COR LOE New, Revised, or Unchanged When considering decompressive suboccipital craniectomy for cerebellar infarction, it may be reasonable to inform family members that the outcome after cerebellar infarct can be good after the surgery. IIb C-LD Recommendation and COR unchanged from 2014 Brain Swelling. Wording revised and LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. 5.2. Seizures COR LOE New, Revised, or Unchanged Recurrent seizures after stroke should be treated in a manner similar to when they occur with other acute neurological conditions, and antiseizure drugs should be selected on the basis of specific patient characteristics. I C-LD Recommendation reworded for clarity from 2013 AIS Guidelines. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. 2. Prophylactic use of antiseizure drugs is not recommended. III: No Benefit C-LD Recommendation reworded for clarity from 2013 AIS Guidelines. COR and LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. 6. In-Hospital Institution of Secondary Stroke Prevention The recommendations in this section reference other current AHA guidelines for secondary stroke prevention where applicable (Table 10). These other guidelines should be referred to for further information on secondary stroke prevention not covered in this document. These other guidelines are updated regularly, and the most recent versions should be used. Table 10.


These other guidelines are updated regularly, and the most recent versions should be used. Table 10. Guidelines Relevant to Secondary Stroke Prevention Document Title Year Published Abbreviation Used in This Document Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association 10 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines 18 Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice AACVPR indicates American Association of Cardiovascular and Pulmonary Rehabilitation; AAPA, American Academy of Physician Assistants; ABC, Association of Black Cardiologists; ACC, American College of Cardiology; ACPM, American College of Preventive Medicine; ADA, American Diabetes Association; AGS, American Geriatrics Society; AHA, American Heart Association; APhA, American Pharmacists Association; ASH, American Society of Hypertension; ASPC, American Society for Preventive Cardiology; N/A, not applicable; NLA, National Lipid Association; NMA, National Medical Association; and PCNA, Preventive Cardiovascular Nurses Association. 5.1.4. Surgical Management-Cerebellar Infarction (Continued) COR LOE New, Revised, or Unchanged Powers et al 2019 Guidelines for Management of AIS e389 6.1. Brain Imaging 6.1. Brain Imaging COR LOE New, Revised, or Unchanged For prevention of recurrent stroke, the use of MRI is reasonable in some patients with AIS to provide additional information to guide selection of appropriate secondary stroke prevention treatments. IIa C-EO New recommendation.


Brain Imaging COR LOE New, Revised, or Unchanged For prevention of recurrent stroke, the use of MRI is reasonable in some patients with AIS to provide additional information to guide selection of appropriate secondary stroke prevention treatments. IIa C-EO New recommendation. NCCT scanning of patients with acute stroke is effective for the detection of acute ICH and the avoidance of antithrombotic treatment in these patients.85 In many patients, the diagnosis of ischemic stroke can be made accurately on the basis of the clinical presentation and either a negative NCCT or one showing early ischemic changes, which can be detected in the majority of patients with careful attention.82,83,298 Many RCTs that provide the current best evidence for secondary stroke prevention treatments did not require MRI for patient selection.207,210,216,219,299 306 The benefits shown in these RCTs can be expected when the same eligibility criteria are applied without the addition of MRI. DW-MRI is more sensitive than CT for detecting AIS,70,71 but there are inadequate data at this time to identify which patients will benefit from brain MRI in addition to or instead of NCCT to improve effectiveness of treatment for prevention of recurrent stroke.


DW-MRI is more sensitive than CT for detecting AIS,70,71 but there are inadequate data at this time to identify which patients will benefit from brain MRI in addition to or instead of NCCT to improve effectiveness of treatment for prevention of recurrent stroke. A systematic review in 2012 identified almost no direct evidence that MRI affects outcome in patients with stroke and limited evidence that MRI affects management.307 A decision-analytical model of patients with TIA and minor stroke concluded that routine use of MRI did not improve outcome except for patients presenting at >1 week after symptoms to diagnose hemorrhage.308 Two studies from the 1990s evaluating repeat neuroimaging recommended repeat CT over additional MRI for most clinical situations in AIS with the exceptions of documenting lacunar and infratentorial infarcts, but they did not present evidence of a benefit on outcome for For instance, 2 situations in which MRI can be useful to select treatments that have been demonstrated by RCTs to improve outcome are (1) patients with carotid stenosis who are potential candidates for carotid revascularization in whom NCCT or neurological examination (eg, pure motor hemiparesis) does not permit accurate localization and (2) patients with patent foramen ovale (PFO) who are potential candidates for mechanical closure (see below). See Tables XVIII and LXXIII in online Data Supplement 1. Brain MRI is reasonable in selected patients as part of a comprehensive evaluation to determine if they meet the eligibility criteria of the RCTs that investigated mechanical closure of PFO for prevention of recurrent stroke. IIa B-R New recommendation. Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria that required brain MRI, imaging of the intracranial vasculature, and echocardiography.


Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria that required brain MRI, imaging of the intracranial vasculature, and echocardiography. Meta-analyses of these trials show a significantly reduced risk of recurrent stroke with mechanical closure compared with medical therapy with a number needed to treat of 131.318 320 A network meta-analysis concluded that, in patients <60 years of age, PFO closure probably confers an important reduction in ischemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure also incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.319 Each of these 6 trials had 1 methodological features with a high risk of bias identified, including lack of blinding of participants and personnel, lack of blinding of outcome assessments, incomplete outcome data, and selective See Tables LXXV through LXXVII in online Data Supplement 1. The effectiveness of routine brain MRI to guide treatment selection for prevention of recurrent stroke is uncertain. (See knowledge byte following 6.1, recommendation 1.) IIb B-NR New recommendation. 6.2. Vascular Imaging 6.2. Vascular Imaging COR LOE New, Revised, or Unchanged For patients with nondisabling (mRS score 0 2) AIS in the carotid territory who are candidates for CEA or stenting, noninvasive imaging of the cervical carotid arteries should be performed routinely within 24 hours of admission. I B-NR New recommendation.


Vascular Imaging COR LOE New, Revised, or Unchanged For patients with nondisabling (mRS score 0 2) AIS in the carotid territory who are candidates for CEA or stenting, noninvasive imaging of the cervical carotid arteries should be performed routinely within 24 hours of admission. I B-NR New recommendation. Past data have indicated that the risk of recurrent stroke caused by symptomatic carotid stenosis is highest early after the initial event.325 329 Although there is evidence that early or emergency revascularization via either CEA or carotid angioplasty and stenting may be safe in selected cases,330 332 there are no high-quality prospective data supporting early versus late carotid revascularization in all cases.333 In cases of nondisabling stroke, a meta-analysis by De Rango demonstrates high rates of complications when treated <48 hours after the initial event and no difference in risks when treated between 0 and 7 days and 0 and 15 days. Revascularization between 48 hours and 7 days after initial stroke is supported by the data in cases of nondisabling stroke (mRS score 0 2).334 Imaging within 24 hours of admission is feasible and recommended to facilitate CEA/carotid angioplasty and stenting in eligible patients in the 48- to 72-hour window. See Table LXXVIII in online Data Supplement 1. For prevention of recurrent stroke, the use of intracranial vessel imaging is reasonable in some patients with AIS to provide additional information to guide selection of appropriate secondary stroke prevention treatments. IIa C-EO New recommendation. An extensive literature search did not yield adequate data to identify subgroups of patients with AIS for whom information obtained from intracranial vessel imaging will lead to improved outcome. There is no RCT evidence that patients with AIS and symptomatic intracranial stenosis should be treated differently from other patients with ischemic stroke of presumed atherosclerotic cause.


There is no RCT evidence that patients with AIS and symptomatic intracranial stenosis should be treated differently from other patients with ischemic stroke of presumed atherosclerotic cause. In the WASID RCT (Warfarin-Aspirin Symptomatic Intracranial Disease), warfarin provided no benefit over aspirin 325 mg/d, even in those who were taking antithrombotics at the time of the qualifying event.335 The SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) showed no benefit of adding Wingspan stenting to aggressive medical therapy that included aspirin 325 mg/d and clopidogrel 75 mg/d for 90 days after enrollment, again even in those who were taking antithrombotics at the time of qualifying event.336 338 The CHANCE trial, which compared dual antiplatelet treatment with clopidogrel and aspirin and aspirin alone for 21 days in patients with high-risk TIA and minor stroke, showed no evidence of preferential benefit from dual antiplatelet treatment in patients with intracranial arterial stenosis. Compared with pooled historical control subjects in WASID, the medical treatment only group in SAMMPRIS had an almost 2-fold lower risk of any stroke or death within 30 days or ischemic stroke in the territory of the qualifying artery after 30 days. Whether this was the result of dual antiplatelet treatment with aspirin and clopidogrel for 90 days remains to be demonstrated by an RCT.337 339 See Tables LXXIX and LXXX in online Data Supplement 1. Imaging of the intracranial vasculature to detect atherosclerotic stenosis of a major intracranial artery is reasonable in selected patients as part of a comprehensive evaluation to determine if they meet the eligibility criteria of the RCTs that investigated mechanical closure of PFO for prevention of recurrent stroke. IIa B-R New recommendation.


Imaging of the intracranial vasculature to detect atherosclerotic stenosis of a major intracranial artery is reasonable in selected patients as part of a comprehensive evaluation to determine if they meet the eligibility criteria of the RCTs that investigated mechanical closure of PFO for prevention of recurrent stroke. IIa B-R New recommendation. Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria that required brain MRI, imaging of the intracranial vasculature, and echocardiography. Meta-analyses of these trials show a significantly reduced risk of recurrent stroke with mechanical closure compared with medical therapy with a number needed to treat of 131.318 320 A network meta-analysis concluded that, in patients <60 years of age, PFO closure probably confers an important reduction in ischemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure also incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.319 Each of these 6 trials had 1 methodological features with a high risk of bias identified, including lack of blinding of participants and personnel, lack of blinding of outcome assessments, incomplete outcome data, and selective See Tables LXXV through LXXVII in online Data Supplement 1. Routine imaging of the intracranial vasculature to detect atherosclerotic stenosis of a major intracranial artery to guide selection of antithrombotic or intracranial endovascular treatment for prevention of recurrent stroke is not well established. (See knowledge byte following 6.2, recommendation 2.) IIb B-NR New recommendation. 6.3. Cardiac Evaluation 6.3.1. Electrocardiographic Monitoring COR LOE New, Revised, or Unchanged Cardiac monitoring is recommended to screen for atrial fibrillation and other potentially serious cardiac arrhythmias that would necessitate emergency cardiac interventions.


Electrocardiographic Monitoring COR LOE New, Revised, or Unchanged Cardiac monitoring is recommended to screen for atrial fibrillation and other potentially serious cardiac arrhythmias that would necessitate emergency cardiac interventions. Cardiac monitoring should be performed for at least the first 24 hours. I B-NR Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. Further support for this unchanged recommendation from the 2013 AIS Guidelines is provided by 2 additional studies published since the 2013 guidelines. Kallm nzer et al340 prospectively monitored by cardiac telemetry 501 patients with acute stroke (92% with cerebral ischemia) for a median of 73 hours after admission to a dedicated stroke unit. A total of 139 serious arrhythmias were detected in 126 patients (25.1%). Atrial fibrillation accounted for 24 of 139 (17%) of the arrhythmias. Detection of arrhythmia led to direct antiarrhythmic treatment in 77.7%. In that study, 52.2% of all detected arrhythmias occurred within 12 hours and 74.4% within 24 hours after admission. Fern ndez- Men ndez et al341 prospectively monitored by cardiac telemetry for a minimum of 48 hours 332 patients admitted to the stroke unit with a diagnosis of ischemic stroke, TIA, or intraparenchymal hemorrhage (90% with cerebral ischemia) admitted within 48 hours of symptom onset. One hundred seventy-four significant cardiac arrhythmias occurred in 98 patients (29.5%). Atrial fibrillation/flutter accounted for 23 of 174 (13%) of the arrhythmias. Thirty- three of 98 (34%) patients were directly treated for the arrhythmia (excluding anticoagulation for atrial fibrillation). Thirty-seven percent of all detected arrhythmias occurred on day 1, 29% on day 2, and 15% on day 3.341 See Table LXXXI in online Data Supplement 1. 6.2.


Thirty-seven percent of all detected arrhythmias occurred on day 1, 29% on day 2, and 15% on day 3.341 See Table LXXXI in online Data Supplement 1. 6.2. Vascular Imaging (Continued) COR LOE New, Revised, or Unchanged Powers et al 2019 Guidelines for Management of AIS e391 The effectiveness of prolonged cardiac monitoring during hospitalization after AIS to guide treatment selection for prevention of recurrent stroke is uncertain. IIb C-LD New recommendation. In patients with TIA or ischemic stroke and atrial fibrillation detected by routine ECG at the time or within the preceding 24 months, oral anticoagulation begun within 3 months is superior to aspirin for the prevention of vascular death, stroke, MI, and systemic embolism (HR, 0.60 [95% CI, 0.41 0.87]).342 With prolonged cardiac monitoring during hospitalization, atrial fibrillation is newly detected in nearly a quarter of patients with stroke or TIA.343 No RCTs have specifically evaluated the benefit of anticoagulation in patients with brief episodes of subclinical atrial fibrillation detected in hospital after AIS. In CRYSTAL AF (Study of Continuous Cardiac Monitoring to Assess Atrial Fibrillation After Cryptogenic Stroke), at 36 months, atrial fibrillation was detected in 30% of 221 patients with implantable cardiac monitors and in 3% of 220 control subjects (P<0.001), but the occurrence of TIA or ischemic stroke was 9% in the implantable cardiac monitor group and 11% in the control group (P=0.64).344,345 In Find-AFRANDOMISED (Finding Atrial Fibrillation in Stroke Evaluation of Enhanced and Prolonged Holter Monitoring), atrial fibrillation was detected in 14% of 200 patients with 10-day Holter monitoring at baseline, 3 months, and 6 months versus 5% of 198 patients in the standard care group who had at least 24 hours of rhythm monitoring (P=0.002).


In CRYSTAL AF (Study of Continuous Cardiac Monitoring to Assess Atrial Fibrillation After Cryptogenic Stroke), at 36 months, atrial fibrillation was detected in 30% of 221 patients with implantable cardiac monitors and in 3% of 220 control subjects (P<0.001), but the occurrence of TIA or ischemic stroke was 9% in the implantable cardiac monitor group and 11% in the control group (P=0.64).344,345 In Find-AFRANDOMISED (Finding Atrial Fibrillation in Stroke Evaluation of Enhanced and Prolonged Holter Monitoring), atrial fibrillation was detected in 14% of 200 patients with 10-day Holter monitoring at baseline, 3 months, and 6 months versus 5% of 198 patients in the standard care group who had at least 24 hours of rhythm monitoring (P=0.002). There was no significant difference in recurrent stroke at 12 months (3.7% versus 5.4%; P=0.46).346 Other smaller studies have also failed to show a difference in outcomes.347 349 All of these studies were underpowered for the secondary clinical end points. Randomized trials are ongoing to determine whether oral anticoagulation therapy compared with aspirin reduces the risk of stroke or systemic embolism in patients with permanent pacemakers, defibrillators, or insertable cardiac monitors who have subclinical atrial fibrillation or high-rate episodes and additional risk factors (NCT01938248, NCT02618577). See Tables LXXXII through LXXXIV in online Data Supplement 1. 6.3.2. Echocardiography COR LOE New, Revised, or Unchanged For prevention of recurrent stroke, the use of echocardiography is reasonable in some patients with AIS to provide additional information to guide selection of appropriate secondary stroke prevention. IIa C-EO New recommendation. In many patients, appropriate evidence-based treatment for secondary prevention can be selected without the use of echocardiography. Many RCTs that provide the current best evidence for secondary prevention treatments did not require echocardiography for patient selection.


Many RCTs that provide the current best evidence for secondary prevention treatments did not require echocardiography for patient selection. These include NASCET (North American Symptomatic Carotid Endarterectomy Trial), ECST (European Carotid Surgery Trial), IST, SALT (Swedish Aspirin Low-dose Trial), CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events), ESPS2 (European Stroke Prevention Study 2), PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes), CHANCE, PROGRESS (Perindopril Protection Against Recurrent Stroke Study), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), SOCRATES, POINT, and TARDIS (Triple Antiplatelets for Reducing Dependency After Ischaemic Stro The benefits shown in these RCTs can be expected when the same eligibility criteria are applied. Those patients with known or newly discovered atrial fibrillation by routine ECG will benefit from oral anticoagulation regardless of echocardiographic findings.342 Intracardiac thrombus occurs almost exclusively in patients with clinical evidence of heart disease but is rare even in them. Echocardiography for detecting intracardiac thrombus in unselected patients will produce at least as many false-positive as true-positive diagnoses.351 In large series of patients with AIS who underwent echocardiography, the reported yield of important potentially cardioembolic sources has ranged from 0.2% to 55% (Table LXXXV in online Data Supplement 1). Much of this discrepancy is the result of differences in categorization of cardiac pathology as either pathophysiologically or therapeutically relevant. The efficacy of treatment in reducing the risk of recurrent stroke associated with many of these echocardiographic lesions is unknown, or there is not a treatment that has been shown to be better than standard medical therapy.352 360 Different authors have concluded that routine echocardiography is indicated or contraindicated.


The efficacy of treatment in reducing the risk of recurrent stroke associated with many of these echocardiographic lesions is unknown, or there is not a treatment that has been shown to be better than standard medical therapy.352 360 Different authors have concluded that routine echocardiography is indicated or contraindicated. Various inconsistent recommendations for selecting which patients with AIS should undergo echocardiography have been made.358,361 363 Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without an obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria. They do not support the routine use of echocardiography in all patients with AIS. See Tables LXXIV and LXXXV in online Data Supplement 1. Echocardiography is reasonable in selected patients as part of a comprehensive evaluation to determine if they meet the eligibility criteria of the RCTs that investigated mechanical closure of PFO for prevention of recurrent stroke. IIa B-R New recommendation. Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without an obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria that required brain MRI, imaging of the intracranial vasculature, and echocardiography. Meta-analyses of these trials show a significantly reduced risk of recurrent stroke with mechanical closure compared with medical therapy with a number needed to treat of 131.318 320 A network meta-analysis concluded that, in patients <60 years of age, PFO closure probably confers an important reduction in ischemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure also incurs a risk of persistent atrial fibrillation and device-related adverse events.


PFO closure also incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.319 Each of these 6 trials had 1 methodological features with a high risk of bias identified, including lack of blinding of participants and personnel, lack of blinding of outcome assessments, incomplete outcome data, and selective reporting.318 324 See Tables LXXV through LXXVII in online Data Supplement 1. 6.3.1. Electrocardiographic Monitoring (Continued) COR LOE New, Revised, or Unchanged The effectiveness of routine echocardiography to guide treatment selection for prevention of recurrent stroke is uncertain. (See knowledge byte following 6.3.2, recommendation 1.) IIb B-NR New recommendation. 6.4. Glucose COR LOE New, Revised, or Unchanged After AIS, it is reasonable to screen all patients for diabetes mellitus with testing of fasting plasma glucose, hemoglobin A1c , or an oral glucose tolerance test. Choice of test and timing should be guided by clinical judgment and recognition that acute illness may temporarily perturb measures of plasma glucose. In general, hemoglobin A1c may be more accurate than other screening tests in the immediate postevent period. IIa C-EO Recommendation wording modified from 2014 Secondary Prevention to match COR IIa stratifications and reworded for clarity. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. 6.5. Other Tests for Secondary Prevention 6.5. Other Tests for Secondary Prevention COR LOE New, Revised, or Unchanged The usefulness of screening for thrombophilic states in patients with ischemic stroke is unknown. IIb C-LD Recommendation reworded for clarity from 2014 Secondary Prevention. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording.


See Table XCV in online Data Supplement 1 for original wording. Current evidence suggests that there is little, if any, contribution of the inherited thrombophilias to the development of arterial thrombotic events. Therefore, tests for inherited thrombophilia should not be ordered for the evaluation of MI, stroke, or peripheral arterial thrombosis.364,365 Routine screening of patients with recent ischemic stroke for obstructive sleep apnea (OSA) is not recommended. III: No Benefit B-R New recommendation. Numerous studies have established an association between OSA and stroke. OSA is highly prevalent among ischemic stroke patients and has been associated with considerable morbidity, including increased risk of cardiovascular and cerebrovascular events, worse prognosis, and higher mortality. Continuous positive airway pressure (CPAP) remains the most effective medical therapy for OSA.366 370 A small RCT of CPAP in 127 patients started 4.6 2.8 days after AIS showed mixed results with no effect on disability, total cardiovascular events, cardiovascular mortality, or cardiovascular event free survival but a reduction in time to first cardiovascular event during 24-month follow-up. This trial did not specify a primary end point and compared multiple different outcomes at multiple time points.371 The SAVE RCT (Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease) randomized 2717 patients with established cardiovascular or cerebrovascular disease (but not within the first 90 days after a stroke except for minor strokes) and moderate to severe OSA to CPAP versus usual care without CPAP and found no reduction of vascular events, including stroke, in patients treated with CPAP over a mean follow-up of Thus, the routine screening for OSA of all patients with AIS for the secondary prevention of cardiovascular events or death is not recommended at this time.


This trial did not specify a primary end point and compared multiple different outcomes at multiple time points.371 The SAVE RCT (Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease) randomized 2717 patients with established cardiovascular or cerebrovascular disease (but not within the first 90 days after a stroke except for minor strokes) and moderate to severe OSA to CPAP versus usual care without CPAP and found no reduction of vascular events, including stroke, in patients treated with CPAP over a mean follow-up of Thus, the routine screening for OSA of all patients with AIS for the secondary prevention of cardiovascular events or death is not recommended at this time. Several ongoing National Institutes of Health funded RCTs are further investigating the effects of CPAP in patients with AIS and OSA (NR018335, NS099043). See Table LXXXVI in online Data Supplement 1. Routine testing for antiphospholipid antibodies is not recommended for patients with ischemic stroke who have no other manifestations of the antiphospholipid syndrome and who have an alternative explanation for their ischemic event such as atherosclerosis, carotid stenosis, or atrial fibrillation. III: No Benefit C-LD Recommendation reworded for clarity from 2014 Secondary Prevention. COR and LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. Routine screening for hyperhomocysteinemia among patients with a recent ischemic stroke is not indicated. III: No Benefit C-EO Recommendation reworded for clarity from 2014 Secondary Prevention. COR and LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. 6.3.2. Echocardiography (Continued) COR LOE New, Revised, or Unchanged Powers et al 2019 Guidelines for Management of AIS e393 6.6. Antithrombotic Treatment 6.6.1.


Echocardiography (Continued) COR LOE New, Revised, or Unchanged Powers et al 2019 Guidelines for Management of AIS e393 6.6. Antithrombotic Treatment 6.6.1. Noncardioembolic Stroke COR LOE New, Revised, or Unchanged For patients with noncardioembolic AIS, the use of antiplatelet agents rather than oral anticoagulation is recommended to reduce the risk of recurrent stroke and other cardiovascular events. I A Recommendation reworded for clarity from 2014 Secondary Prevention. COR and LOE unchanged. See Table XCV in online Data Supplement 1 for original wording. For early secondary prevention in patients with noncardioembolic AIS, the selection of an antiplatelet agent should be individualized on the basis of patient risk factor profiles, cost, tolerance, relative known efficacy of the agents, and other clinical characteristics. I C-EO Recommendation reworded for clarity from 2014 Secondary Prevention. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. For patients who have a noncardioembolic AIS while taking aspirin, increasing the dose of aspirin or switching to an alternative antiplatelet agent for additional benefit in secondary stroke prevention is not well established. IIb B-R Recommendation revised from 2014 Secondary Prevention. In patients with a noncardioembolic ischemic stroke, the therapeutic benefit of aspirin is similar across a wide range of doses, but the hemorrhagic risk increases with higher doses. In patients taking aspirin at the time of the incident stroke, the benefit of switching to an alternative antiplatelet agent or combination therapy is not well established. The SPS3 RCT (Secondary Prevention of Small Subcortical Strokes) found no benefit from adding clopidogrel to aspirin compared with placebo in patients with a recent small vessel, lacunar stroke taking aspirin at the time of their index event.


The SPS3 RCT (Secondary Prevention of Small Subcortical Strokes) found no benefit from adding clopidogrel to aspirin compared with placebo in patients with a recent small vessel, lacunar stroke taking aspirin at the time of their index event. However, the median time from the qualifying event to enrollment in the SPS3 trial was >40 days, so results may have underestimated benefit in the early poststroke period.373 A recent meta-analysis of 5 studies, including 3 RCTs and 2 observational registries, of patients with noncardioembolic stroke taking aspirin at the time of the index event found a decreased risk of major cardiovascular events and recurrent stroke in patients switching to an alternative antiplatelet agent or combination antiplatelet therapy. This analysis included data from aspirin failure subgroups in the CHANCE trial of dual antiplatelet therapy in patients with minor stroke or TIA and the SOCRATES trial of aspirin versus ticagrelor. However, there was significant heterogeneity among the included studies, and results may have been driven by data from registries susceptible to unmeasured confounders and bias.374 See Tables LXXXVII and LXXXVIII in online Data Supplement 1. Anticoagulation might be considered in patients who are found to have abnormal findings on coagulation testing after an initial ischemic stroke, depending on the abnormality and the clinical circumstances. IIb C-LD Recommendation reworded for clarity from 2014 Secondary Prevention. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. For patients who have a noncardioembolic AIS while taking antiplatelet therapy, switching to warfarin is not indicated for secondary stroke prevention. III: No Benefit B-NR New recommendation.