Muhammad Fawad Ishfaq

Blood pressure levels post mechanical thrombectomy and outcomes in large vessel occlusion strokes

Objective: There are limited data evaluating the effect of post mechanical thrombectomy (MT) blood pressure (BP) levels on early outcomes of patients with large vessel occlusions (LVO). We sought to investigate the association of BP course following MT with early outcomes in LVO. Methods: Consecutive patients with LVO treated with MT during a 3-year period were evaluated. Hourly systolic BP (SBP) and diastolic BP (DBP) values were recorded for 24 hours following MT and maximum SBP and DBP levels were identified. LVO patients with complete reperfusion following MT were stratified in 3 groups based on post-MT achieved BP goals: <140/90 mm Hg (intensive), <160/90 mm Hg (moderate), and <220/110 mm Hg or <180/105 mm Hg when pretreated with IV thrombolysis (permissive hypertension). Three-month functional independence was defined as modified Rankin Scale score of 0–2. Results: A total of 217 acute ischemic stroke patients with LVO were prospectively evaluated. A 10 mm Hg increment in maximum SBP documented during the first 24 hours post MT was independently (p = 0.001) associated with a lower likelihood of 3-month functional independence (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.56–0.87) and a higher odds of 3-month mortality (OR 1.49; 95% CI 1.18–1.88) after adjusting for potential confounders. In addition, achieving a BP goal of <160/90 mm Hg during the first 24 hours following MT was independently associated with a lower likelihood of 3-month mortality (OR 0.08; 95% CI 0.01–0.54; p = 0.010) in comparison to permissive hypertension. Conclusions: High maximum SBP levels following MT are independently associated with increased likelihood of 3-month mortality and functional dependence in LVO patients. Moderate BP control is also related to lower odds of 3-month mortality in comparison to permissive hypertension.

Admission systolic blood pressure and outcomes in large vessel occlusion strokes treated with endovascular treatment

Background and purpose High admission blood pressure (BP) levels have been associated with lower recanalization rates after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO). We sought to evaluate the association of admission BP with early outcomes in patients with ELVO treated with EVT. Methods Consecutive patients with AIS presenting with ELVO in a tertiary stroke center during a 4-year period were prospectively evaluated. Admission systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using automated cuff recordings. A blinded neuroradiologist calculated the final infarct volume (FIV) using standardized ABC/2 methodology. A favorable functional outcome (FFO) at 3 months was defined as modified Rankin Scale score of 0–2. Results Our study population consisted of 116 patients with AIS (mean age 63±13 years, median NIH Stroke Scale score 17 points (IQR 14–21), median FIV 30 cm3 (IQR 8–94)). Higher admission SBP correlated with higher FIV (r +0.225; p=0.020). Patients with FFO had lower admission SBP (151±24 mm Hg vs 165±28 mm Hg; p=0.010), while admission SBP levels were higher in patients who died during hospitalization (169±34 mm Hg vs 156±24 mm Hg; p=0.043). A 10 mm Hg increment in admission SBP was independently (p=0.010) associated with an increase of 12 cm3 in FIV (95% CI 3 to 21) in multiple linear regression models adjusting for potential confounders. A 10 mm Hg increment in admission SBP was independently (p=0.012) associated with a lower likelihood of FFO at 3 months (OR 0.64; 95% CI 0.45 to 0.91) in multiple logistic regression models adjusting for potential confounders. Conclusions Higher admission SBP is an independent predictor of increased FIV and lower likelihood of 3-month FFO in patients with ELVO treated with EVT.

Cerebral Microbleeds and Risk of Intracerebral Hemorrhage Post Intravenous Thrombolysis

BACKGROUND Stroke patients who have cerebral micro bleeds (CMBs) could be potentially at a greater risk for symptomatic intracerebral hemorrhage (sICH) than those patients without CMBs. The aim of our study was to investigate whether the presence and burden of CMBs are associated with post IVT sICH. METHODS In this multicenter study, consecutive patients treated with intravenous tissue plasminogen activator were prospectively identified and analyzed. Patients without magnetic resonance imaging (MRI) within 24 hours of treatment were excluded. CMBs were defined as round or oval, hypointense lesions with associated blooming on T2*-weighted MRI up to 10 mm in diameter. Outcome measures included the occurrence of sICH or death. RESULTS Of 672 patients with IVT (mean age 62 ± 14 years, 52% men, median admission NIHSS: 7 points), 103 patients had CMBs on T2*-MRI. Ten patients had more than 10, whereas the remaining 93 patients had 1-10 CMBs on T2*-MRI. The rates of sICH did not differ between patients with and patients without 1-10 CMBs (5.8% versus 3.5%; P = .27). However, sICH occurred more frequently (P = .0009) in patients with > 10 CMBs (30%, 95% confidence interval [CI] by the adjusted Wald method: 10%-61%). After adjusting for potential confounders, the presence of >10 CMBs on T2*-MRI was independently (P = .0004) associated with a higher likelihood for sICH (odds ratio [OR]:13.4, 95%CI:3.2-55.9). CONCLUSIONS Our findings indicate an increased risk of sICH after IVT when more than 10 CMBs are present.

Cerebrovascular Outcomes With Proton Pump Inhibitors and Thienopyridines: A Systematic Review and Meta-Analysis

Background and Purpose— Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes. Methods— We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders. Results— We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41–2.16; P<0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01–1.29; P=0.04), and MI (risk ratio, 1.19; 95% CI, 1.00–1.40; P=0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04–1.61; P=0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03–1.47; P=0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93–1.52; P=0.16). Conclusions— Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines.

Hemicraniectomy versus Conservative Treatment in Large Hemispheric Ischemic Stroke Patients: A Meta-analysis of Randomized Controlled Trials

BACKGROUND Several small trials have inconclusively evaluated the effect of hemicraniectomy in reducing death and disability in acute ischemic stroke patients with large hemispheric infarctions. We compared the effects of hemicraniectomy on death and disability with conservative treatment in patients with large hemispheric infarctions. METHODS We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using random-effects models from 7 randomized trials that compared hemicraniectomy with conservative treatment in acute ischemic stroke patients. The primary end point was a favorable outcome defined by modified Rankin Scale grades of 0 (no symptoms), 1 (no significant disability), 2 (slight disability), and 3 (moderate disability) at 6-12 months post randomization. RESULTS Of the 341 total subjects randomized, the proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to hemicraniectomy than among those randomized to conservative treatment (OR 2.04, 95% CI 1.03-4.03, P = .04). Survival was also significantly greater among those randomized to hemicraniectomy (OR 5.56, 95% CI 3.40-9.08, P < .001) than among those randomized to conservative treatment. There was a trend toward higher odds of favorable outcome among those randomized to hemicraniectomy than among those randomized to conservative treatment in trials that permitted recruitment of patients aged 60 years or older (303 subjects analyzed; OR 1.87, 95% CI .91-3.86, P = .09). CONCLUSIONS Compared with conservative treatment, the odds of achieving a favorable outcome at 6 months is approximately 2-folds higher with hemicraniectomy in patients with large hemispheric infarctions.

O-008 Comparison between tici 2b and tici 3

Background Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients with emergent large-vessel occlusions (ELVO) has become the standard of care. A recent meta-analysis of the 5 randomized trials demonstrated that 46% of patients in the intervention arm achieved mRS of 0–2 at 3 months. Considering the fact that significant numbers of patients still have residual disability at three months despite MT, it is important to consider other modifiable variables that might improve functional outcomes in patients with ELVO. Successful reperfusion post MT is the strongest modified predictor of the outcome. Thrombolysis in cerebral infarction (TICI) grades are current standard of care for assessment of degree of reperfusion post MT. Recently conducted trials defined both TICI 2b and 3 grades as successful reperfusion. In this multicenter study we sought to evaluate if there are any differences in safety and effectiveness outcomes between ELVO patients who achieved TICI 2b and those who achieved TICI 3 reperfusion post MT. Methods We conducted an observational study on consecutive AIS patients with ELVO who underwent MT at 6 high-volume endovascular centers. Standard safety (3 month mortality, symptomatic intracranial hemorrhage) and effectiveness (3 month functional independence: modified Rankin Scale scores of 0–2) outcomes were compared between patients who had TICI 2b and TICI 3 reperfusion post MT. Results The sample consisted of 583 patients with ELVO who underwent MT. A total of 416 patients achieved successful reperfusion (TICI 2b or 3) post MT. TICI 2b reperfusion was achieved in 216 (52%) patients [mean age 64±15, Male 50%, median NIHSS: 16 (IQR 12–20)], while 200 patients (48%) achieved TICI 3 reperfusion post MT [mean age 66±14, Male, 48%, median NIHSS 16 (IQR: 13–20)]. TICI 2b and TICI 3 reperfusion groups did not differ in terms of intravenous thrombolysis pretreatment (51% vs 56%, p=0.425), median onset to groin puncture time [minutes, median (IQR); 223 (157–318) vs 240 (176–311), p=0.850], median groin puncture to recanalization time [minutes, median (IQR); 38 (23–62 vs 41 (26–57), p=0.282) and 3 months mortality (22% vs 19%, p=0.523). TICI 3 reperfusion group had lower median discharge NIHSS [median (IQR) 3 (1–7) vs 5 (2-12), p=0.029), lower rates of symptomatic intracranial hemorrhage (6% vs 12%, p=0.035) and higher rates of functional independence at 3 months (55% vs 44%, p=0.050) compared to TICI 2b reperfusion group. In multivariate model after adjustment for potential confounders, TICI 3 reperfusion group was associated with greater neurological improvement during hospitalization (OR 1.009; 95% CI: 1.002–1.016, p=0.024), lower rates of sICH (OR 0.28; 95% CI: 0.10–0.78, p=0.027) and tended to have higher rates of 3 months functional independence (OR 1.80; 95% CI; 1.01–3.21, p=0.054) compared to TICI 2b group. Conclusions TICI 3 reperfusion appears to be associated with better early outcomes in comparison to TICI 2b reperfusion in ELVO Patients treated with MT. Future clinical trials involving ELVO patients should differentiate between these reperfusion groups in terms of safety and effectiveness outcomes. Disclosures N. Goyal: None. G. Tsivgoulis: None. D. Frei: None. A. Turk: None. B. Baxter: None. M. Froehler: None. J. Mocco None. M. Ishfaq: None. D. Hoit: None. J. Chang: None. L. Elijovich: None. D. Loy: None. R. Turner: None. J. Mascitelli: None. K. Espaillat: None. A. Alexandrov: None. A. Arthur: None.

Antiplatelet pretreatment and outcomes following mechanical thrombectomy for emergent large vessel occlusion strokes

Background Few data are available regarding the safety and efficacy of antiplatelet (APT) pretreatment in acute ischemic stroke (AIS) patients with emergent large vessel occlusions (ELVO) treated with mechanical thrombectomy (MT). We sought to evaluate the association of APT pretreatment with safety and efficacy outcomes following MT for ELVO. Methods Consecutive ELVO patients treated with MT during a 4-year period in a tertiary stroke center were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), successful recanalization (SR; modified TICI score 2b/3), mortality, and functional independence (modified Rankin Scale scores of 0–2). Results The study population included 217 patients with ELVO (mean age 62±14 years, 50% men, median NIH Stroke Scale score 16). APT pretreatment was documented in 71 cases (33%). Patients with APT pretreatment had higher SR rates (77% vs 61%; P=0.013). The two groups did not differ in terms of sICH (6% vs 7%), 3-month mortality (25% vs 26%), and 3-month functional independence (50% vs 48%). Pretreatment with APT was independently associated with increased likelihood of SR (OR 2.18, 95% CI1.01 to 4.73; P=0.048) on multivariable logistic regression models adjusting for potential confounders. A significant interaction (P=0.014) of intravenous thrombolysis (IVT) pretreatment on the association of pre-hospital antiplatelet use with SR was detected. APT pretreatment was associated with SR (OR 2.74, 95% CI 1.15 to 6.54; P=0.024) in patients treated with combination therapy (IVT and MT) but not in those treated with direct MT (OR 1.78, 95% CI 0.63 to 5.03; P=0.276). Conclusion APT pretreatment does not increase the risk of sICH and may independently improve the odds of SR in patients with ELVO treated with MT. The former association appears to be modified by IVT.

Prehospital and Emergency Department Management of Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke and a critical disease usually leading to severe disability or death. Around 20% of patients with ICH will experience a decrease in the Glasgow Coma Scale of two or more points between the prehospital assessment and the initial evaluation in the emergency department (ED). Therefore, aggressive prehospital and ED treatment is cornerstone for effective management of patients with ICH. Initial management should focus on urgent stabilization of cardiorespiratory variables and treatment of intracranial complications. Recent technological innovations have opened new perspectives for stroke diagnosis and treatment before the patient arrives at the hospital. These prehospital measures include presumed stroke diagnosis by paramedics, mobile telemedicine for remote clinical examination and imaging, mobile stroke units with integrated computerized tomography (CT) scanners, point-of-care laboratories in ambulances, and prehospital notification provided by emergency medical staff (EMS). Primary management of ICH in ED includes rapid clinical evaluation, laboratory studies including blood glucose and coagulation defects, diagnostic imaging studies, management of blood pressure and early intracranial complications such as hydrocephalus or impending herniation, and admission to stroke unit or neuroscience intensive care unit (NICU). In this book chapter, we will discuss in detail about various prehospital and ED management strategies for management of patients with ICH.

Comparative Safety and Efficacy of Modified TICI 2b and TICI 3 Reperfusion in Acute Ischemic Strokes Treated With Mechanical Thrombectomy

BACKGROUND Mechanical thrombectomy (MT) is the current standard of care for acute ischemic stroke (AIS) patients with emergent large-vessel occlusions (ELVO). Successful reperfusion of ELVO is traditionally defined by modified Thrombolysis in Cerebral Infarction (mTICI) grades of 2b or 3. OBJECTIVE To evaluate the comparative safety and efficacy of mTICI 2b and mTICI 3 reperfusion in AIS patients treated with MT. METHODS Consecutive ELVO patients who underwent MT at 6 high-volume centers were included in this analysis. Standard safety (3-mo mortality, symptomatic intracranial hemorrhage [sICH]) and efficacy (absolute and relative reduction in NIHSS-scores during hospitalization, functional-improvement [shift analysis in mRS-scores], and functional-independence [mRS-scores of 0-2] at 3-mo) were compared between patients who had mTICI 2b and mTICI 3 reperfusion post MT. RESULTS A total of 416 ELVO patients achieved successful reperfusion with mTICI 2b (n = 216) and mTICI 3 (n = 200) following MT. The mTICI 3 group had significantly (P < .05) greater absolute (11 vs 9 points) and relative (77% vs 63%) reduction in NIHSS-scores during hospitalization, lower sICH (6% vs 12%), and higher 3-mo functional-independence (55% vs 44%) rates. Successful reperfusion with mTICI 3 was independently (P < .05) associated with greater absolute and relative reduction in NIHSS-scores during hospitalization as well as higher odds of 3-mo functional improvement (common odds ratios: 1.67; 95% confidence interval: 1.10-2.56) and functional independence (odds ratio: 2.08; 95% confidence interval: 1.22-3.53) in multivariable regression models adjusting for confounders. CONCLUSION Successful reperfusion with mTICI 3 was associated with greater neurological improvement during hospitalization and better 3-mo functional outcomes in comparison to mTICI 2b reperfusion.

The association of adult vaccination with the risk of cerebrovascular ischemia: A systematic review and meta-analysis

There is mounting evidence supporting infection as an independent risk factor for ischemic stroke (IS), while preliminary data indicate that vaccination may prevent IS. We performed a systematic review and meta-analysis of available randomized clinical trials (RCTs) or prospective observational cohorts reporting associations of influenza vaccination (IV) and/or pneumococcal vaccination (PV) with IS. We identified a total of 12 studies (543,311 patients; 47.4% vaccinated). Vaccination was not related to the risk of IS (RR=1.06, 95%CI: 0.74-1.51, p=0.77), with no significant differences (p=0.26) among RCTs (RR=0.66, 95%CI: 0.30-1.47) and observational studies (RR=1.11, 95%CI: 0.76-1.61). Evidence of considerable heterogeneity was identified within observational studies (I2=98%), but not within RCTs (I2=0%). In subgroup analyses according to vaccination type, IV was associated with a significantly lower risk of IS (RR=0.87, 95%CI: 0.79-0.96, p=0.004) with moderate evidence of heterogeneity (I2=53%). No association was seen for PV (RR=1.38, 95%CI: 0.60-3.16, p=0.45), where considerable heterogeneity was identified (I2=97%). In the additional adjusted analyses of observational studies, vaccination tended to be associated with lower risk of IS (HRadjusted=0.87; 95%CI: 0.75-1.01; p=0.07). The findings of this meta-analysis indicate that IV may be associated with a lower risk of IS. This association was not reproduced for PV or the combination of two vaccines. Substantial heterogeneity was detected across observational studies for all outcome events, while moderate to low heterogeneity was identified across included RCTs. These preliminary findings require independent validation in large RCTs.