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.


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. In patients taking aspirin at the time of baseline stroke in WARSS (Warfarin Aspirin Recurrent Stroke Study; n=181), there was no difference in recurrence of stroke between those randomized to remain on aspirin and those who In addition, post hoc analysis from the WASID trial found no difference in the primary outcome of ischemic stroke, brain hemorrhage, or vascular death in patients taking antiplatelet therapy at the time of their qualifying event who were subsequently randomized to warfarin.376,377 See Table LXXXIX in online Data Supplement 1. In patients with noncardioembolic ischemic stroke, treatment with triple antiplatelet therapy (aspirin+clopidogrel+dipyridamole) for secondary stroke prevention is harmful and should not be administered. III: Harm B-R New recommendation. The TARDIS trial (N=3096) was a multicenter, prospective, randomized, open-label trial conducted in Denmark, Georgia, New Zealand, and the United Kingdom of short-term triple antiplatelet therapy for secondary stroke prevention in patients with recent noncardioembolic ischemic stroke or TIA.350 The open-label treatment arms included aspirin+clopidogrel+dipyridamole versus either clopidogrel alone or aspirin and dipyridamole for 30 days from symptom onset. There was no benefit of triple therapy in prevention of stroke or TIA at 90 days (6% versus 7%; HR, 0.90 [95% CI, 0.67 1.20]; P=0.47). Moreover, there was a significant increase in risk of all hemorrhage (20% versus P=0.0063), and extracranial hemorrhage (HR, 2.37; 95% CI, 1.93 2.91; P<0.0001). See Table XLVIII in online Data Supplement 1. 6.6.2. Atrial Fibrillation COR LOE New, Revised, or Unchanged For most patients with an AIS in the setting of atrial fibrillation, it is reasonable to initiate oral anticoagulation between 4 and 14 days after the onset of neurological symptoms.


Atrial Fibrillation COR LOE New, Revised, or Unchanged For most patients with an AIS in the setting of atrial fibrillation, it is reasonable to initiate oral anticoagulation between 4 and 14 days after the onset of neurological symptoms. IIa B-NR Recommendation revised from 2014 Secondary Prevention. A multicenter prospective cohort of 1029 patients with AIS and newly diagnosed atrial fibrillation showed a better composite outcome of stroke, TIA, systemic embolism, sICH, and major extracranial bleeding within 90 days when anticoagulant was initiated 4 to 14 days from stroke onset (HR 0.53 [95% CI, 0.30 0.93] for starting anticoagulation at 4 14 days compared with <4 days); high CHA2 -VASc score, high NIHSS score, large ischemic lesions, and type of anticoagulation were associated with poorer outcomes.378 In a prospective, open-label study of 60 patients with atrial fibrillation and either mild to moderate AIS with NIHSS score <9 (n=49) or TIA (n=11) who were treated with rivaroxaban within14 days of onset, 50 were available for follow-up at 7 days after drug initiation. None developed symptomatic hemorrhagic transformation (HT). Of the 23 with AIS who had HT at baseline, 5 demonstrated asymptomatic radiographic progression, and 18 showed neither clinical nor radiographic progression. Of the remaining 27 who did not have HT at baseline, 3 developed asymptomatic HT.227 See Table LI in online Data Supplement 1. For patients with a history of ischemic stroke, atrial fibrillation, and coronary artery disease, the usefulness of adding antiplatelet therapy to oral anticoagulants is uncertain for purposes of reducing the risk of ischemic cardiovascular and cerebrovascular events. Unstable angina and coronary artery stenting represent special circumstances in which management may warrant dual antiplatelet/oral anticoagulation. IIb C-LD Recommendation reworded for clarity from 2014 Secondary Prevention. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System.


LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. 6.6.3. Arterial Dissection COR LOE New, Revised, or Unchanged For patients with AIS and extracranial carotid or vertebral arterial dissection, treatment with either antiplatelet or anticoagulant therapy for 3 to 6 months is reasonable. IIa B-NR Recommendation revised from 2014 Secondary Prevention. Although there has not been a randomized trial of antithrombotic therapy versus placebo in patients with acute cervical artery dissection (CeAD), numerous observational studies and expert opinion suggest that it is reasonable to initiate antithrombotic therapy in the acute setting to prevent early thromboembolic events. The CADISS (Cervical Artery Dissection in Stroke Study) group published a randomized, open-label phase II feasibility trial of anticoagulation versus antiplatelet therapy in 250 participants with extracranial carotid or vertebral artery dissection recruited from 46 centers in the United Kingdom and Australia.379 The primary outcome was ipsilateral stroke or all-cause mortality within 3 months of randomization in an intention-to-treat analysis, and there were no significant differences between groups. There was also no difference in rates of major bleeding. As a phase II trial, the study concluded that a definitive phase III trial would not be feasible, primarily because of the low event rates in both groups. Additional limitations included a lack of central radiological confirmation in 20% of cases and a mean time to randomization of 3.65 days that perhaps limits generalizability of the results to the hyperacute period. Nonetheless, the CADISS trial supports numerous previous observational studies that found no significant difference in clinical outcomes with the use of anticoagulation compared with antiplatelet therapy in patients with CeAD.


Nonetheless, the CADISS trial supports numerous previous observational studies that found no significant difference in clinical outcomes with the use of anticoagulation compared with antiplatelet therapy in patients with CeAD. In addition, in a follow-up CADISS analysis of dissecting aneurysms (DAs), there was no association between treatment allocation (antiplatelets versus anticoagulants) and whether DAs at baseline persisted at follow-up or whether new DAs developed. During 12 months of follow-up, stroke occurred in 1 of 48 patients with DA and in 7 of 216 patients without DA (age- and sex-adjusted OR, 0.84 [95% CI, 0.10 7.31]; P=0.88). A review of published studies, mainly retrospective, showed a similarly low risk of stroke and no evidence of an increased stroke rate in patients with DA.380 These data provide evidence that DAs may have a benign prognosis, and therefore, medical treatment should be considered. See Tables LI and XC in online Data Supplement 1. For patients with AIS and extracranial carotid or extracranial vertebral arterial dissection who have definite recurrent cerebral ischemic events despite medical therapy, the value of extracranial EVT (stenting) is not well established. IIb C-LD Recommendation revised from 2014 Secondary Prevention. There have been no controlled trials of EVT and stenting in patients with extracranial CeAD. The published literature reflects small case series, individual case reports, and several systematic reviews.381 A systematic review of the literature published until 2009 found 31 published reports (N=140) with a technical success rate of 99% and procedural complication rate of 1.3%. However, these observational data are prone to selection and reporting biases. A retrospective analysis of patients with CeAD (n=161) comparing extracranial EVT (with and without stenting) with medical therapy alone found no difference in 90-day outcomes (adjusted OR, 0.62 [95% CI, 0.12 3.14]; P=0.56).


A retrospective analysis of patients with CeAD (n=161) comparing extracranial EVT (with and without stenting) with medical therapy alone found no difference in 90-day outcomes (adjusted OR, 0.62 [95% CI, 0.12 3.14]; P=0.56). With medical therapy alone, the overall prognosis and natural history of CeAD, including DAs, are favorable.379,380 Therefore, the benefit of extracranial EVT and stenting in patients with CeAD and definite recurrent cerebral ischemic events despite medical therapy is not well established. See Table LI in online Data Supplement 1. Powers et al 2019 Guidelines for Management of AIS e395 6.6.4. Hemorrhagic Transformation COR LOE New, Revised, or Unchanged For patients with AIS and HT, initiation or continuation of antiplatelet or anticoagulation therapy may be considered, depending on the specific clinical scenario and underlying indication. IIb C-LD Recommendation revised from 2014 Secondary Prevention. Several observational studies suggest that antithrombotics can be safely initiated or continued in patients with AIS and HT. In a prospective, open-label study of 60 patients with atrial fibrillation and either mild to moderate AIS with an NIHSS score <9 (n=49) or TIA (n=11) who were treated with rivaroxaban within 14 days of onset, 50 were available for follow-up at 7 days after drug initiation. None developed symptomatic HT. Of the 23 with AIS who had HT at baseline, 5 demonstrated asymptomatic radiographic progression, and 18 showed neither clinical nor radiographic progression. Of the remaining 27 who did not have HT at baseline, 3 developed asymptomatic HT.227 A retrospective stroke registry analysis identified 222 patients with AIS and HT. The frequency of composite events (neurological deterioration, vascular events, and death) at 1 month was significantly lower in patients treated with antithrombotics compared with those who were not (1.6% versus 11.1%; P=0.041).


The frequency of composite events (neurological deterioration, vascular events, and death) at 1 month was significantly lower in patients treated with antithrombotics compared with those who were not (1.6% versus 11.1%; P=0.041). Neither antiplatelet (n=72) nor anticoagulant (n=28) treatment after HT was associated with enlargement of the original HT or development of new HT or neurological deterioration.382 Individual assessment of the clinical indication, benefits, and associated risks is warranted.10,382,383 See Table LI in online Data Supplement 1. 6.7. Carotid Revascularization 6.7. Carotid Revascularization COR LOE New, Revised, or Unchanged When revascularization is indicated for secondary prevention in patients with minor, nondisabling stroke (mRS score 0 2), it is reasonable to perform the procedure between 48 hours and 7 days of the index event rather than delay treatment if there are no contraindications to early revascularization. IIa B-NR Recommendation revised from 2014 Secondary Prevention. The risk of recurrent stroke resulting from symptomatic carotid stenosis is highest in the first few days after the initial 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 minor, nondisabling stroke, a meta-analysis by De Rango et demonstrates favorable rates of complications when treated at least 48 hours after the initial event, and the risks are not different when treated between 0 to 7 and 0 to 15 days. Revascularization between 48 hours and 7 days after initial stroke is supported by these data in cases of nondisabling stroke (mRS score 0 2).334 See Table LXXVIII in online Data Supplement 1. 6.8. Treatment of Hyperlipidemia 6.8.1.


Revascularization between 48 hours and 7 days after initial stroke is supported by these data in cases of nondisabling stroke (mRS score 0 2).334 See Table LXXVIII in online Data Supplement 1. 6.8. Treatment of Hyperlipidemia 6.8.1. General Principles COR LOE New, Revised, or Unchanged Patients with AIS should be managed according to the 2018 ACC/AHA Cholesterol Guidelines, which include lifestyle modification, dietary recommendations, and medication recommendations. I A Recommendation, COR, and LOE updated from 2014 Secondary Prevention to reference 2018 Cholesterol Guidelines The 2018 Cholesterol Guidelines provide a comprehensive set of recommendations for managing hyperlipidemia.19 Those recommendations that are most pertinent to the in-hospital management of patients with AIS are excerpted here. The full guidelines should be used for guidance in managing these disorders in patients with AIS and for supporting evidence. In adults who are 20 years of age or older and not on lipid-lowering therapy, measurement of either a fasting or a nonfasting plasma lipid profile is effective in estimating atherosclerotic cardiovascular disease (ASCVD) risk and documenting baseline low-density lipoprotein cholesterol (LDL-C). I B-NR Recommendation unchanged from 2018 Cholesterol Guidelines. Adherence to changes in lifestyle and effects of LDL-C lowering medication should be assessed by measurement of fasting lipids and appropriate safety indicators 4 to 12 weeks after statin initiation or dose adjustment and every 3 to 12 months thereafter based on need to assess adherence or safety. I A Recommendation unchanged from 2018 Cholesterol Guidelines. 6.8.2. Choice of Lipid-lowering Drugs for Patients with Clinical ASCVD* COR LOE New, Revised, or Unchanged In patients who are 75 years of age or younger with clinical ASCVD, high- intensity statin therapy should be initiated or continued with the aim of achieving a 50% or greater reduction in LDL-C levels. I A Recommendation unchanged from 2018 Cholesterol Guidelines.


Choice of Lipid-lowering Drugs for Patients with Clinical ASCVD* COR LOE New, Revised, or Unchanged In patients who are 75 years of age or younger with clinical ASCVD, high- intensity statin therapy should be initiated or continued with the aim of achieving a 50% or greater reduction in LDL-C levels. I A Recommendation unchanged from 2018 Cholesterol Guidelines. In patients with clinical ASCVD in whom high-intensity statin therapy is contraindicated or who experience statin-associated side effects, moderate- intensity statin therapy should be initiated or continued with the aim of achieving a 30% to 49% reduction in LDL-C levels. I A Recommendation unchanged from 2018 Cholesterol Guidelines. In patients at increased ASCVD risk with chronic, stable liver disease (including nonalcoholic fatty liver disease) when appropriately indicated, it is reasonable to use statins after obtaining baseline measurements and determining a schedule of monitoring and safety checks. I B-R Recommendation unchanged from 2018 Cholesterol Guidelines. In patients with clinical ASCVD, who are judged to be very high-risk and considered for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy, maximally tolerated LDL-C lowering therapy should include maximally tolerated statin therapy and ezetimibe. I B-R Recommendation unchanged from 2018 Cholesterol Guidelines. In patients with clinical ASCVD who are judged to be very high risk and who are on maximally tolerated LDL-C lowering therapy with LDL-C 70 mg/dL or higher ( 1.8 mmol/L) or a non HDL-C level of 100 mg/dL or higher ( 2.6 mmol/L), it is reasonable to add a PCSK9 inhibitor following a clinician patient discussion about the net benefit, safety, and cost. IIa A Recommendation unchanged from 2018 Cholesterol Guidelines. At mid-2018 list prices, PCSK9 inhibitors have a low cost value (>$150000 per quality-adjusted life-year) compared to good cost value (<$50000 per quality- adjusted life-year).


At mid-2018 list prices, PCSK9 inhibitors have a low cost value (>$150000 per quality-adjusted life-year) compared to good cost value (<$50000 per quality- adjusted life-year). Value Statement: Low Value (LOE: B-NR) Statement unchanged from 2018 Cholesterol Guidelines. In patients with clinical ASCVD who are on maximally tolerated statin therapy and are judged to be at very high risk and have an LDL-C level of 70 mg/dL or higher ( 1.8 mmol/L), it is reasonable to add ezetimibe therapy. IIa B-R Recommendation unchanged from 2018 Cholesterol Guidelines. In patients older than 75 years of age with clinical ASCVD, it is reasonable to initiate moderate- or high-intensity statin therapy after evaluation of the potential for ASCVD risk reduction, adverse effects, and drug drug interactions, as well as patient frailty and patient preferences. IIa B-R Recommendation unchanged from 2018 Cholesterol Guidelines. In patients older than 75 years of age who are tolerating high-intensity statin therapy, it is reasonable to continue high-intensity statin therapy after evaluation of the potential for ASCVD risk reduction, adverse effects, and drug-drug interactions, as well as patient frailty and patient preferences. IIa C-LD Recommendation unchanged from 2018 Cholesterol Guidelines. In patients with clinical ASCVD who are receiving maximally tolerated statin therapy and whose LDL-C level remains 70 mg/dL or higher ( 1.8 mmol/L), it may be reasonable to add ezetimibe. IIb B-R Recommendation unchanged from 2018 Cholesterol Guidelines. *Clinical ASCVD includes acute coronary syndrome, those with history of MI, stable or unstable angina, or coronary or other arterial revascularization, stroke, TIA, or peripheral artery disease, including aortic aneurysm, all of atherosclerotic origin. For high-intensity statin therapy, the 2018 ACC/AHA Cholesterol Guidelines recommend atorvastatin 80 mg daily or rosuvastatin 20 mg daily. Please refer to these guidelines for contraindications to high-intensity statin therapy and recommendations for moderate-intensity statin therapy.


Please refer to these guidelines for contraindications to high-intensity statin therapy and recommendations for moderate-intensity statin therapy. Very high risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions: Major ASCVD Events: Recent acute coronary syndrome (within the past 12 months) History of MI (other than recent acute coronary syndrome event listed above) History of ischemic stroke Symptomatic peripheral arterial disease (history of claudication with ankle-brachial index <0.85, or previous revascularization or amputation. High-Risk Conditions: Age 65 years Heterozygous familial hypercholesterolemia History of prior coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD events Diabetes mellitus Hypertension Chronic kidney disease (estimated glomerular filtration rate 15 59 mL min 1 ) Current smoking 6.8.2. Choice of Lipid-lowering Drugs for Patients with Clinical ASCVD* (Continued) COR LOE New, Revised, or Unchanged Powers et al 2019 Guidelines for Management of AIS e397 6.8.3 Implementation COR LOE New, Revised, or Unchanged A clinician-patient risk discussion is recommended before initiation of statin therapy to review net clinical benefit, weighing the potential for ASCVD risk reduction against the potential for statin-associated side effects, statin-drug interactions, and safety, while emphasizing that side effects can be addressed successfully. I A Recommendation unchanged from 2018 Cholesterol Guidelines. In patients with indication for statin therapy, identification of potential predisposing factors for statin-associated side effects, including new-onset diabetes mellitus and statin-associated muscle symptoms, is recommended before initiation of treatment. I B-R Recommendation unchanged from 2018 Cholesterol Guidelines. In patients with statin-associated side effects that are not severe, it is recommended to reassess and to rechallenge to achieve a maximal LDL-C lowering by modified dosing regimen, an alternate statin or in combination with nonstatin therapy. I B-R Recommendation unchanged from 2018 Cholesterol Guidelines.


In patients with statin-associated side effects that are not severe, it is recommended to reassess and to rechallenge to achieve a maximal LDL-C lowering by modified dosing regimen, an alternate statin or in combination with nonstatin therapy. I B-R Recommendation unchanged from 2018 Cholesterol Guidelines. In patients at increased ASCVD risk with severe statin-associated muscle symptoms or recurrent statin-associated muscle symptoms despite appropriate statin rechallenge, it is reasonable to use RCT-proven nonstatin therapy that is likely to provide net clinical benefit.384 386 IIa B-R Recommendation unchanged from 2018 Cholesterol Guidelines. 6.8.4. Timing COR LOE New, Revised, or Unchanged Among patients already taking statins at the time of onset of ischemic stroke, continuation of statin therapy during the acute period is reasonable. IIa B-R Recommendation and COR unchanged from 2013 AIS Guidelines. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. For patients with AIS who qualify for statin treatment, in-hospital initiation of statin therapy is reasonable. IIa C-LD New recommendation. Statins have an established role in secondary stroke prevention and harbor promise in improving index stroke A retrospective cohort study that assessed 3-month treatment adherence rates after in-hospital initiation of statins in patients with ischemic stroke showed a high rate of adherence to statin therapy 3 months after hospital discharge.387 A meta-analysis of primarily observational studies found that in-hospital statin use was associated with good functional outcomes.388 Withdrawal of statins after ischemic stroke was associated with poor functional outcomes. There are limited published randomized trials examining the role of early statin use in AIS patients. FASTER (Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence) evaluated simvastatin 40 mg versus placebo in patients with a TIA or minor stroke within Because of slow enrollment, this trial was terminated early.


FASTER (Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence) evaluated simvastatin 40 mg versus placebo in patients with a TIA or minor stroke within Because of slow enrollment, this trial was terminated early. There were no significant differences in recurrent stroke or safety outcomes in the simvastatin versus placebo groups. FASTER was underpowered because of early termination, and the statin doses used in FASTER were of moderate intensity (not the high-intensity dose recommended for secondary stroke prevention). ASSORT (Administration of Statin on Acute Ischemic Stroke Patient) showed no difference in 90-day mRS score when statins were begun within 24 hours or on the seventh day.390 See Tables XCI and XCII in online Data Supplement 1. 6.8.5 Special Patient Groups COR LOE New, Revised, or Unchanged Women of childbearing age who are treated with statin therapy and are sexually active should be counseled to use a reliable form of contraception. I C-LD Recommendation unchanged from 2018 Cholesterol Guidelines. Women of childbearing age with hypercholesterolemia who plan to become pregnant should stop the statin 1 to 2 months before pregnancy is attempted or, if they become pregnant while on a statin, should have the statin stopped as soon as the pregnancy is discovered. I C-LD Recommendation unchanged from 2018 Cholesterol Guidelines. In adults with advanced kidney disease that requires dialysis treatment who are currently on LDL-lowering therapy with a statin, it may be reasonable to continue the statin. IIb C-LD Recommendation unchanged from 2018 Cholesterol Guidelines. In adults with advanced kidney disease who require dialysis treatment, initiation of a statin is not recommended. III: No Benefit B-R Recommendation unchanged from 2018 Cholesterol Guidelines. 6.9. Institution of Antihypertensive Medications 6.9.


III: No Benefit B-R Recommendation unchanged from 2018 Cholesterol Guidelines. 6.9. Institution of Antihypertensive Medications 6.9. Institution of Antihypertensive Medications COR LOE New, Revised, or Unchanged Starting or restarting antihypertensive therapy during hospitalization in patients with BP >140/90 mmHg who are neurologically stable is safe and is reasonable to improve long-term BP control unless contraindicated. IIa B-R New recommendation. Starting or restarting antihypertensive medications has been shown to be associated with improved control of the BP after discharge in 2 trials.247,248 Therefore, it is reasonable to start or restart antihypertensive medications in the hospital when the patient remains hypertensive and is neurologically stable. Studies evaluating this question included only patients with previous diagnosis of hypertension247 or enrolled mostly patients with previous hypertension.248 However, because hypertension is not uncommonly first diagnosed during the hospitalization for stroke, it is reasonable to apply this recommendation also to patients without preexistent hypertension. See Table LVI in online Data Supplement 1. 6.10. Smoking Cessation Intervention 6.10. Smoking Cessation Intervention COR LOE New, Revised, or Unchanged Smokers with AIS should receive in-hospital initiation of high-intensity behavioral interventions to promote smoking cessation. I A New recommendation. For smokers with an AIS, who receive in-hospital initiation of high-intensity behavioral interventions to promote smoking cessation, nicotine replacement therapy is recommended. I A New recommendation. A 2012 meta-analysis by the Cochrane group indicates that high-intensity behavioral interventions that begin during an index hospitalization and include at least 1 month of supportive contact after discharge increased smoking cessation rates after discharge (RR, 1.37 [95% CI, 1.27 1.48]; 25 trials). The estimate of the effect for each level of intervention intensity among patients with a cardiovascular diagnosis was very similar (RR, 1.42 [95% CI, 1.29 1.56]).


The estimate of the effect for each level of intervention intensity among patients with a cardiovascular diagnosis was very similar (RR, 1.42 [95% CI, 1.29 1.56]). Adding nicotine replacement therapy to an intensive counselling intervention increased smoking cessation rates A 2016 retrospective cohort study of Korean smokers with AIS assessed a timely intervention strategy versus historical controls who received Timely intervention comprised a certified nurse providing comprehensive education during admission and additional counseling after discharge. Timely intervention was associated with greater odds of sustained smoking cessation for 12 months. See Table XCIII and XCIV in online Data Supplement 1. Healthcare providers should strongly advise every patient with AIS who has smoked in the past year to quit. 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. It is reasonable to advise patients after ischemic stroke to avoid secondhand (passive) tobacco smoke. IIa B-NR 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 smokers with an AIS, in-hospital initiation of varenicline to promote smoking cessation might be considered. IIb B-R New recommendation. A 2012 meta-analysis by the Cochrane group indicates that high-intensity behavioral interventions that begin during an index hospitalization and include at least 1 month of supportive contact after discharge increased smoking cessation rates after discharge (RR, 1.37 [95% CI, 1.27 1.48]; 25 trials). The estimate of the effect for each level of intervention intensity among patients with a cardiovascular diagnosis was very similar (RR, 1.42 [95% CI, 1.29 1.56]).


The estimate of the effect for each level of intervention intensity among patients with a cardiovascular diagnosis was very similar (RR, 1.42 [95% CI, 1.29 1.56]). There was insufficient direct evidence to conclude that adding bupropion or varenicline to intensive counseling increases cessation rates over what is achieved by counseling alone.391 A subsequent 2016 multicenter, double-blind, randomized, placebo-controlled trial in which 302 smokers hospitalized with an acute coronary syndrome were randomized to varenicline or placebo for 12 weeks showed that at 24 weeks abstinence rates were 47.3% in the varenicline group versus 32.5% in the placebo group. Continuous abstinence rates were 35.8% in the varenicline group versus 25.8% in the placebo group.393 Patients in both groups received low- intensity counseling. See Tables XCIII and XCIV in online Data Supplement 1. Powers et al 2019 Guidelines for Management of AIS e399 6.11. Stroke Education 6.11. Stroke Education COR LOE New, Revised, or Unchanged Patient education about stroke is recommended. Patients should be provided with information, advice, and the opportunity to talk about the impact of the illness on their lives. I C-EO Recommendation and COR unchanged from 2016 Rehab Guidelines. LOE revised. Additional reference support for this guideline is provided in online Data Supplement 1.394 544 Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other William J.