Race and In-Hospital Stroke Care

Intracerebral haemorrhage [ICH] accounts for ~15% of all strokes with an estimated 40% mortality at one month, with higher rates of occurrence among Black patients1. Differences have been observed in the burden of ICH by race, with a higher incidence among Black, Asian and Hispanic compared to White patients2,3.

The number of hospital admissions for ICH in the United States escalated from 150,000 in early 1990s to 175,000 in early 2000s2. Studies have reported racial differences in the quality and process of care among patients hospitalized with ICH4. A recent paper by Cruz-Flores found racial differences in In-hospital utilization of care including lifesaving and life-sustaining therapies, palliative care, do not resuscitate status and in-hospital mortality5.

Two recent studies showed that compared to whites, minority patients were more often younger with higher rates of medical comorbidities, longer length of stay and lower rates of do not resuscitate orders and in-hospital mortality2,5. Rates of hospital admissions have been also shown to be higher among minority men compared to women, however this might be a mere reflection of females not having equal access to care5.

A report on stroke performance measures by Xian in 2014 revealed smoking cessation counselling was less frequently completed among minority patients2. Counseling on modifiable risk factors is a key measure to reduce risk of stroke, recurrent stroke and coronary heart disease. In addition, Xian et al reported that Black patients were less likely than White patients to have a door to CT time of ≤ 25 minutes2. Rapid neuroimaging is one of the key class I recommendations of the American Heart Association/American Stroke Association for ICH patients2,6. Subsequent management is essentially dependent on identification of stroke subtype by neuroimaging. Further research is needed to identify mechanisms and causes of disparities in outcomes after stroke, ICH in particular, among minority patients.



  1. Kleindorfer D, Khoury J, Moomaw CJ, Alwell K, Woo D, Flaherty ML, Khatri P, Adeoye O, Ferioli S, Broderick JP, Kissela BM. Stroke incidence is decreasing in whites, but not in blacks: a population-based estimate of temporal trends in stroke incidence from the Greater Cincinnati/Northern Kentucky stroke study. Stroke; a journal of cerebral circulation. 2010 Jul;41(7):1326.
  2. Xian Y, Holloway RG, Smith EE, et al. Racial/ethnic differences in process of care and outcomes among patients hospitalized with intracerebral hemorrhage. Stroke 2014; 45: 3243–3250.
  3. Woo D, Rosand J, Kidwell C, et al. The ethnic/racial variations of intracerebral hemorrhage (ERICH) study protocol. Stroke 2013; 44: e120–e125.
  4. Cruz-Flores S, Rabinstein A, Biller J, et al. Racial-ethnic disparities in stroke care: the American experience: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 2091–2116.
  5. Cruz-Flores, Salvador, Gustavo J. Rodriguez, Mohammad Rauf A. Chaudhry, Ihtesham A. Qureshi, Mohtashim A. Qureshi, Paisith Piriyawat, Anantha R. Vellipuram, Rakesh Khatri, Darine Kassar, and Alberto Maud. “Racial/ethnic disparities in hospital utilization in intracerebral hemorrhage.” International Journal of Stroke (2019): 1747493019835335.
  6. Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP, Connolly ES Jr, et al; American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010; 41:2108–2129.



Let’s Talk About Race and Stroke Recurrence

There has been a growing body of evidence pointing to potential differences in outcomes of stroke based on race/ethnicity. Recent investigations by Hao et al1, presented at the ISC 19, examined ethnic variation in stroke recurrence, from the angle of intracranial atherosclerotic stenosis [ICAS]. ICAS is estimated to be the underlying pathology in about 15% of ischemic stroke patients2, and is associated with high risk of stroke recurrence even with utmost medical treatment1. The investigators of this study included patients with ICAS in major vessels with >50% stenosis identified on Magnetic resonance angiography or computed tomography angiography. The authors observed higher rate of 3-months as well as long-term recurrence among non-White compared to White patients, although this did not reach statistical significance, possibly due to insufficient power.

Going from ischemic stroke [IS] to intracerebral hemorrhage [ICH], King et al3 assessed recurrence of ICH based on race/ethnicity. They used comprehensive claims data that included hospital discharges in California between 2005-2011. The authors included patients who survived to discharge. Similar to what has been observed in IS, King et al found higher rates of ICH recurrence among Black and Asian compared to White patients.

There are some suggestions on potential explanations on those differences based on the burden of specific clinical conditions by race/ethnicity, such as hypertension4 and chronic kidney disease as reported by Hao et al1. However, this is an area that needs further investigations in representative samples of patients.



[1] Hao, Qing, et al. “Abstract TP157: Ethnic Difference in Stroke Recurrence for Patients With Intracranial Atherosclerotic Stenosis.” Stroke 50.Suppl_1 (2019): ATP157-ATP157.

[2] Bose, Arani, et al. “A novel, self-expanding, nitinol stent in medically refractory intracranial atherosclerotic stenoses: the Wingspan study.” Stroke 38.5 (2007): 1531-1537.

[3] King, Zachary A., et al. “Abstract WMP97: Racial/Ethnic Disparities in the Risk of Intracerebral Hemorrhage Recurrence.” Stroke 50.Suppl_1 (2019): AWMP97-AWMP97.

[4] Rodriguez-Torres, Axana, et al. “Hypertension and intracerebral hemorrhage recurrence among white, black, and Hispanic individuals.” Neurology 91.1 (2018): e37-e44.




Clinical Trials on VCID in Alzheimer’s Disease

This year at ISC19, Dr. Eliezer Masliah MD highlighted key ongoing trials on vascular cognitive impairment and dementia (VCID) in Alzheimer’s disease (AD)1. Currently, there are 140 AD trials at different stages of development covering a wide array of topics that include pharmacological, neuropsychiatric or caregiver interventions. Many of the pharmacological trials target vascular interactions of AD with VCID.

Key ongoing pharmacological trials at early stages include The Calibrex in patients with cognitive impairment at risk of AD2. Another key trial targets blood pressure and vasculature in individuals with mild cognitive impairment. A third trial investigates anti-hypertensive drugs to receptive blockers. This includes a number of anti-hypertensive drugs with neurocognitive function (as the primary outcome) in individuals with already mild cognitive impairment or AD.

Non-pharmacological trials include a study from Minnesota and UC San Diego with 300 participants – these participants are individuals with mild cognitive impairment, or very prodromal stages, that investigate the impact of aerobic exercise on cognition3. There are a number of measurements of blood flow, brain atrophy and other outcomes. Other examples include a trial targeting healthy diet interventions, comparing Mediterranean intervention with or without exercise looking at well-being and global cognition.

Many of the above trials will be reporting between 2019 and 2022, bridging key gaps in clinical management and treatment of VCID and Neurocognitive disorders. For more info on ongoing trials, please refer to: https://www.ninds.nih.gov/Disorders/Clinical-Trials



  1. Masliah, Eliezer. Clinical Trials on VCID in Alzheimer’s Disease. NIH Clinical and Applied Research Programs in Vascular Contributions to Cognitive Impairment and Dementia (VCID) (Joint Government Agency Session) [oral presentation]. In: The International Stroke Conference of the American Heart Association; 2019 Feb 6–8; Honolulu, HI.
  2. gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 -. Identifier NCT01984164, CAndesartan vs LIsinopril Effects on the BrRain (CALIBREX); 2013 Nov 14 [cited 2019 March 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT01984164
  3. gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 -. Identifier NCT03313895, The ACT Trial: Effects of Combined Aerobic Exercise and Cognitive Training in MCI; 2017 Oct 18 [cited 2019 March 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT03313895



Follow Your Heart But Take Your Mind With You: Insights on Vascular Dementia

Cardiovascular diseases such as diabetes and hypertension are established risk factors for mild cognitive impairment (MCI) and vascular dementia (VD). Vascular pathology occurs alongside neurodegenerative disease pathology, and both are associated with interactive effects on the clinical presentation of VD1. Several cardiovascular risk factors of VD could be modified during the preclinical course of the disease during midlife rather than later in life or closer to VD onset2,3.

In this year at ISC19, Angela L. Jefferson reported results supporting that age-related aortic stiffness contributes to transmission of damaging pulsatility and reduction in blood flow. This contributes to blood brain barrier compromise, resulting in reduced cerebral perfusion and subsequent tissue damage4. Brain MRI results suggest that vascular dysregulation may drive neurodegeneration over time, possibly due to neurofibrillary tangle formation or synaptic degradation4.

Looking from another angle, Lawrence J. Fine presented on the interplay between CVD and VD in epidemiological studies. According to data from the American Heart Association, loss of a perfect cardiovascular health during midlife is concurrently associated with steep increase in risk of MCI and vascular dementia. A recent report from the Women Health Initiative Memory Study (WHIMS) assessed MCI and Parkinson’s disease (PD) in women with myocardial infarction (MI). The data suggests modest absolute numbers, but higher rates of MCI and Parkinson’s disease (PD) cases in women with myocardial infarction (MI) (adjusted HR for PD or MCI was 2.23, 95% CI 1.51 to 3.30)5.

Investigators of the SprintMind trial examined the effect of one or more intensive high blood pressure treatment than is currently recommended. SprintMind was a randomized controlled trial that compared intensive treatment (goal SBP < 120 mm hg) to standard treatment (goal SBP < 140 mm Hg). Patients with major CVD as strokes, diabetes and congestive heart failure were excluded. The results suggest that intensive blood pressure control causes no harm on cognition with actual reduction in MCI risk compared to standard treatment6.

Overall, these observations add novel insights on the association between CVD and VD. More data is needed to assess the extent to which CVD contributes to the occurrence of MCI and dementia in more diverse populations and over longer follow-up periods.



  1. Yaffe, Kristine. “Prevention of cognitive impairment with intensive systolic blood pressure control.” Jama (2019).
  2. Gottesman, Rebecca F., et al. “Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) cohort.” Jama neurology 74.10 (2017): 1246-1254.
  3. Gottesman, Rebecca F., et al. “Association between midlife vascular risk factors and estimated brain amyloid deposition.” Jama 317.14 (2017): 1443-1450.
  4. Jefferson, Angela L., et al. “Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.” Circulation 138.18 (2018): 1951-1962.
  5. Haring, Bernhard, et al. “Cardiovascular Disease and Cognitive Decline in Postmenopausal Women: Results from the Women’s Health Initiative Memory Study.” Journal of the American Heart Association 2.6 (2013): e000369.
  6. Williamson, Jeff D. “A randomized trial of intensive versus standard systolic blood pressure control and the risk of mild cognitive impairment and dementia: results from SPRINT MIND.” Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association 14.7 (2018): P1665-P1666.




How Far Can We Go in the Early Management of Acute Ischemic Stroke?

(In anticipation of the International Stroke Conference 2019 – ISC19)

Not so long ago, the benefit of endovascular thrombectomy beyond six hours of ischemic stroke onset was uncertain, particularly among patients with ischemic brain tissue that has not yet undergone infarction. The volume of irreversibly injured ischemic tissue and the volume of brain tissue that is ischemic, but not yet infarcted, could be assessed by computed tomographic perfusion imaging or a combination of diffusion and perfusion magnetic resonance imaging.1,2

Early last year, the DAWN3 and DEFUSE 34 trials’ investigators presented findings at ISC18 that lead to immediate change in the guidelines5 with substantial implications for prevention of functional dependence among stroke survivors.

The DAWN trial was a multicentre, prospective, randomized, open labelled trial conducted at 26 centers in the United States, Canada, Europe and Australia, with at least 40 mechanical thrombectomy procedures performed annually. Patients were enrolled if they were last known to be well within 6 to 24 hours earlier and had occlusion of the intracranial internal carotid artery or proximal middle cerebral artery with a mismatch between the severity of clinical deficit and the infarct volume. The mismatch criteria were defined according to age, stroke severity, occlusion site, time to treatment and type of stroke onset. Primary end points included mean score for disability and functional independence at 90 days.

The mean score on the utility-weight modified Rankin scale and rate of functional independence at 90 days were 5.5 and 49% in the thrombectomy group, compared to 3.4 and 13% in the control group. The rate of symptomatic intracranial haemorrhage and death at 90 days did not differ between the two groups.

The DEFUSE 3 trial was a multicentre, randomized, open labelled trial that included 38 centers in the United States. Patients were enrolled if they were last known to be well within 6 to 16 hours and had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral artery or internal carotid artery occlusion, an initial infarct size of less than 70ml and ratio of ischemic tissue to infarct volume of 1.8 or more were randomly assigned to thrombectomy plus standard medical therapy or standard medical therapy alone. The primary outcome was the ordinal score on the modified Rankin scale at 90 days.

The 90-days mortality rate was 14% in the endovascular therapy group compared to 26% in the medical therapy group. The absolute difference in functional independence between groups was 28% points, indicating a better 90 day functional outcomes compared to patients who had standard medical therapy alone. This mainly applies to patients who had evidence of salvageable tissue determined on the basis of a formula that incorporates early infarct size and the volume of hypoperfused tissue on perfusion imaging.

The incidence of symptomatic cerebral haemorrhage was not statistically different, yet numerically higher in the endovascular compared to the medical therapy group. Mortality was numerically lower in the endovascular therapy group. In between group differences of 24-hour infarct volume and growth after thrombectomy were not significant. Further, patients treated within six hours after stroke onset had favourable outcomes compared to other trials. This difference could be attributed to the favourable collateral circulation and slower infarct growth in patients recruited in the DEFUSE 3 trial.

Enrollment in the DAWN trial was stopped at 31 months, because the results of an interim analysis met the prespecified criterion for trial discontinuation, which was a predictive probability of superiority of thrombectomy of at least 95% for the first primary end point. Similarly, the DEFUSE 3 trial was terminated early for efficacy after 182 patients had undergone randomization, given the interim analysis results exceeded the prespecified efficacy boundary (P<0.0025). Both the DAWN and DEFUSE 3 trials used the same automated perfusion software (RAPID) to measure the volume of early infarct and hypoperfused volume.

Further advancements are anticipated at ISC19, with key questions on benefits beyond those time points and among the broader population of ischemic stroke survivors.



  1. Albers GW, Goyal M, Jahan R, et al. Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME. Ann Neurol 2016. 79: 76-89.
  2. Wheeler HM, Mlynash M, Inoue M, et al. Early diffusion-weighted imaging and perfusion-weighted imaging lesion volumes forecast final infarct size in DEFUSE2. Stroke 2013. 44: 681
  3. Nogueira, Raul G., et al. “Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct.” New England Journal of Medicine 2018. 378:11-21.
  4. Albers, Gregory W., et al. “Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging.” New England Journal of Medicine 378: 708-718.
  5. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018. 39:46-99.




Can We Use Observational Data To Improve Clinical Management of Stroke Patients?

Randomized clinical trials (RCTs) contributed the most to our knowledge to date in management of stroke patients. Despite the strengths of RCTs, they can be very costly and sometimes not feasible.

In this year AHA Scientific Sessions, Jonathan P. Piccini, MD highlighted areas where observational data have been informative to address difficult clinical questions that couldn’t be addressed by RCTs alone. Key areas include: the role of bleeding scores in guiding stroke prevention treatment decisions1, withholding oral anticoagulation in patients with significant contraindications2, the role of oral anticoagulants in improving prognosis of patients with end-stage renal disease3, and the role of concomitant aspirin in improving outcomes in patients on oral anticoagulant therapy4. Thus, there are many examples where observational data provided key insights in management of stroke patients (from a clinical epidemiology perspective) on risk factors, disease progression, treatment utilization and its patterns, comparative safety and effectiveness. Most importantly, those investigations were key to highlight knowledge gaps and generate hypotheses to guide or build on existing RCTs data.

Moving forward, to further advance the translation of observational data to clinical practice, there is a need for: 1) collaborative efforts to merge diverse observational data sets, and 2) more focused investigations to refine our analytical methods with specific applications in the stroke population.



  1. Pisters, R., Lane, D. A., Nieuwlaat, R., De Vos, C. B., Crijns, H. J., & Lip, G. Y. (2010). A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.Chest138(5), 1093-1100.
  2. Shah, M., Avgil Tsadok, M., Jackevicius, C. A., Essebag, V., Eisenberg, M. J., Rahme, E., … & Pilote, L. (2014). Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis.Circulation129(11), 1196-1203.
  3. Pokorney, S. D., Simon, D. N., Thomas, L., Gersh, B. J., Hylek, E. M., Piccini, J. P., & Peterson, E. D. (2016). Stability of international normalized ratios in patients taking long-term warfarin therapy.Jama316(6), 661-663.
  4. Hsu, J. C., Maddox, T. M., Kennedy, K. F., Katz, D. F., Marzec, L. N., Lubitz, S. A., … & Marcus, G. M. (2016). Oral anticoagulant therapy prescription in patients with atrial fibrillation across the spectrum of stroke risk: insights from the NCDR PINNACLE registry.JAMA cardiology1(1), 55-62.



Management of Stroke Patients: A One Man Show or A Tag-Team?

Atrial fibrillation (AF) increases risk of stroke up to 5 folds, resulting in considerable physical, cognitive impairment and high mortality1. Thus, AF related strokes are very expensive to treat compared to non-AF strokes2. Oral anticoagulation is a well-established therapy in the majority of stroke cases3. Warfarin reduces the risk of stroke by 64% and mortality by 30% compared to placebo3.

Recent data from the pinnacle registry presented by ‘Roopinder Sandhu, Edmonton, AB, Canada’ at the Scientific Sessions 2018, highlighted three key challenges in anti-coagulants management in stroke patients4. Data from a national outpatient registry reported over 700,000 patients had a diagnosis of atrial fibrillation5. Although oral anticoagulation use increased over time, around 40% of patients who are eligible for anti-coagulation never got started on therapy5. The second gap is sub-therapeutic dosing. Recent data from the orbit registry evaluated over 5700 patients who were recently started on a new drug and reported that one in eight patients were either underdosed or overdosed6. Further, there was a higher rate of adverse events in patients who had dosing that was sub therapeutic. The third gap is non-adherence. Data from administrative claims based on a large U.S. commercial insurance database, calculated adherence based on the fill date and the days of supply on the pharmacy claims over a median of 1.1 years7. Less than half of patients who were started on a drug therapy reached the threshold of proportion days covered of 80% or higher. This proportion was less for patients who were on Warfarin.

Given the public health consequences of untreated AF, it is necessary to evaluate different strategies to deliver stroke prevention therapy. Data from 30 randomized clinical trials evaluating the impact of pharmacists, versus standard care, showed superior results in the pharmacist care group in reducing systolic blood pressure (by 8 mm HG), diastolic blood pressure (by 4 mm HG) and total cholesterol (by 17 milligrams DL) and LDL (by 13 mg DL)10. This was done through educational intervention and identification of drug related problems followed by early feedback to the treating physician.

Roopinder added a few possible explanations to what could be driving such impact in the Canadian setting. Typically, a general practitioner would be dealing with patients with a higher evidence of chronic diseases. Further, patient demands often exceed the available physician capacity.

While these results collectively suggest that pharmacist led strategies may be a promising way forward because of their accessibility, drug expertise and their ability to build a trusted relationship. A few key things should be considered. First, that anticoagulation remains to be a complicated problem when it comes to individual patients, with many factors playing a role in the decision process including; medical history (as prior bleeding) and patient preferences. Second, while these interventions seem beneficial in the short-term it may lead to the same shortcomings in the long-term with the increase in demand on the pharmacists as the main provider.

Finally, a key question remains, would a collaborative approach between physicians and pharmacists yield better outcomes through reducing the burden on both providers and simultaneously increasing the time allocated to stroke patients on a case-by-case basis?



  1. Developed with the special contribution of the European Heart Rhythm Association (EHRA), Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), Authors/Task Force Members, Camm, A. J., Kirchhof, P., Lip, G. Y., … & Al-Attar, N. (2010). Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). European heart journal31(19), 2369-2429.
  2. Stewart, S., Murphy, N., Walker, A., McGuire, A., & McMurray, J. J. V. (2004). Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart90(3), 286-292.
  3. Ruff, C. T., Giugliano, R. P., Braunwald, E., Hoffman, E. B., Deenadayalu, N., Ezekowitz, M. D., … & Yamashita, T. (2014). Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. The Lancet383(9921), 955-962.
  4. Sandhu, R. K., Guirguis, L. M., Bungard, T. J., Youngson, E., Dolovich, L., Brehaut, J. C., … & McAlister, F. A. (2018). Evaluating the potential for pharmacists to prescribe oral anticoagulants for atrial fibrillation. Canadian Pharmacists Journal/Revue des Pharmaciens du Canada151(1), 51-61.
  5. Marzec, L. N., Wang, J., Shah, N. D., Chan, P. S., Ting, H. H., Gosch, K. L., … & Maddox, T. M. (2017). Influence of direct oral anticoagulants on rates of oral anticoagulation for atrial fibrillation. Journal of the American College of Cardiology69(20), 2475-2484.
  6. Steinberg, B. A., Peterson, E. D., Kim, S., Thomas, L., Gersh, B. J., Fonarow, G. C., … & Piccini, J. P. (2015). Use and outcomes associated with bridging during anticoagulation interruptions in patients with atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Circulation131(5), 488-494.
  7. Yao, X., Abraham, N. S., Alexander, G. C., Crown, W., Montori, V. M., Sangaralingham, L. R., … & Noseworthy, P. A. (2016). Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. Journal of the American Heart Association5(2), e003074.
  8. Santschi, V., Chiolero, A., Burnand, B., Colosimo, A. L., & Paradis, G. (2011). Impact of pharmacist care in the management of cardiovascular disease risk factors: a systematic review and meta-analysis of randomized trials. Archives of internal medicine171(16), 1441-1453.