Blood Pressure Level and Variability During Long-Term Prasugrel or Clopidogrel Medication After Stroke

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

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Day-by-Day Blood Pressure Variability in the Subacute Stage of Ischemic Stroke and Long-Term Recurrence

Stroke ◽

10.1161/strokeaha.120.033751 ◽

2021 ◽

Author(s):

Kenji Fukuda ◽

Ryu Matsuo ◽

Masahiro Kamouchi ◽

Fumi Kiyuna ◽

Noriko Sato ◽

...

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Recurrent Stroke ◽

Competing Risk ◽

Risk Of Death ◽

Subacute Stage ◽

Increased Risk ◽

Day By Day

Background and Purpose: This study aimed to determine whether variability of day-by-day blood pressure (BP) during the subacute stage of acute ischemic stroke is predictive of long-term stroke recurrence. Methods: We analyzed 7665 patients (mean±SD age: 72.9±13.1 years; women: 42.4%) hospitalized for first-ever ischemic stroke in 7 stroke centers in Fukuoka, Japan, from June 2007 to November 2018. BP was measured daily during the subacute stage (4–10 days after onset). Its mean and coefficient of variation (CV) values were calculated and divided into 4 groups according to the quartiles of these BP parameters. Patients were prospectively followed up for recurrent stroke or all-cause death. The cumulative event rate was calculated with the Kaplan-Meier method. We estimated the hazard ratios and 95% confidence intervals of the events of interest after adjusting for potential confounders and mean BP values using Cox proportional hazards models. The Fine-Gray model was also used to account for the competing risk of death. Results: With a mean (±SD) follow-up duration of 3.9±3.2 years, the rates of recurrent stroke and all-cause death were 3.9 and 9.9 per 100 patient-years, respectively. The cumulative event rates of recurrent stroke and all-cause death increased with increasing CVs of systolic BP and diastolic BP. The systolic BP CV was significantly associated with an increased risk of recurrent stroke after adjusting for multiple confounders and mean BP (hazard ratio [95% CI] for fourth quartile versus first quartile, 1.26 [1.05–1.50]); the risk of recurrent stroke also increased with an increasing systolic BP CV for nonfatal strokes (1.26 [1.05–1.51]) and when death was regarded as a competing risk (1.21 [1.02–1.45]). Similar associations were observed for the diastolic BP CV. Conclusions: Day-by-day variability of BP during the subacute stage of acute ischemic stroke was associated with an increased long-term risk of recurrent stroke.

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Abstract P132: Clinical Outcomes In Ischemic Stroke Patients With Uncontrolled Hypertension

Hypertension ◽

10.1161/hyp.78.suppl_1.p132 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Zahra Abuzaid ◽

Sara Almuslem ◽

Farah Aleisa

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Clinical Outcomes ◽

Recurrent Stroke ◽

Uncontrolled Hypertension ◽

Stroke Recurrence ◽

Stroke Patients ◽

Stroke Event ◽

Uncontrolled Blood Pressure

Background: Hypertension is considered major risk factor for incidence of ischemic stroke, controlling blood pressure reduces this risk, the relationship of uncontrolled blood pressure and stroke outcomes is complex, post stroke uncontrolled blood pressure remains one of the major contributing factors for stroke recurrence and mortality, in our study we studied the long term effects of uncontrolled hypertension in modern health care setting. Methodology: Patients in the study were admitted to the neurology department at KFSH-D between March 2015- August 2019, we included 102 acute ischemic stroke patients whom had hypertension, all patients had follow up appointments at stroke clinic a minimum of 2 visits over 4 years. We retrospectively compared blood pressure data from stroke patients with recurrent ischemic stroke events vs. patients with initial stroke event, and recurrent stroke, also we studied blood pressure readings for different stroke severity groups, patients who had severe stroke with mRS>4, compared to milder stroke group of mRS<4. Results: We found 48 patients identified with recurrent stroke event, those with uncontrolled hypertension had significantly higher stroke recurrence events (P=0.002), despite acute stroke treatment, patients who had history of uncontrolled hypertension were found to have more severe stroke deficits than those who had controlled blood pressure (P=0.029). We found significant difference in the long term stroke clinical outcomes between patients who had uncontrolled blood pressure and patients who had controlled blood pressure recordings within the same hospital setting (P=0.064). Conclusion: Based on our findings, uncontrolled hypertension was associated with higher risk of stroke recurrence, it also increased susceptibility to worse stroke clinical outcomes up to 1 year after initial stroke event, which deserved further close attention and better blood pressure control.

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Long-term stroke incidence in proximal thoracic aorta aneurysm survivors

International Journal of Stroke ◽

10.1177/1747493019840944 ◽

2019 ◽

Vol 15 (4) ◽

pp. 421-428

Author(s):

Jin-Yi Hsu ◽

Yuan-Chih Su ◽

Jen-Hung Wang ◽

Boon Lead Tee

Keyword(s):

Ischemic Stroke ◽

Thoracic Aorta ◽

Hemorrhagic Stroke ◽

Study Cohort ◽

Research Database ◽

Term Care ◽

Term Survival ◽

Stroke Incidence ◽

Increased Risk

Background Aneurysm of proximal thoracic aorta (pTAA) is an often indolent, yet fatal disease. Although advancements in aneurysmal repair techniques have increased long-term survival rates, studies have proven that there are increases in perioperative risk for stroke incidence after pTAA surgery. Conversely, there is little evidence regarding the long-term stroke incidence in pTAA individuals, which strongly influences the morbidity, mortality, and usage of antithrombotic agents. Methods Using the Taiwan National Health Insurance Research Database, a nationwide population-based cohort, we recruited 3013 pTAA survivors hospitalized from 1 January 2000 to 31 December 2012. To ensure study cohort quality, only patients aged 20 years and above who underwent aneurysmal repair surgery are included. The control cohort is identified by matching background features (comorbidities, age, gender) at a 1:4 ratio through the use of frequency matching. The primary outcomes include incidence of ischemic stroke and intracranial hemorrhage one month after aneurysmal repair surgery. Results The mortality of pTAA survivors is nearly twice of the matched controls despite aneurysmal repair (28.5 % vs. 15.2%, p < 0.001). Long-term follow-up of participants indicated that pTAA survivors had a higher risk for hemorrhage stroke (adjusted hazard ratio (aHR): 1.93; 95% confidence interval (CI): 1.47–2.53), but no significant increase in risk for ischemic stroke (aHR: 1.07; 95% CI: 0.92–1.25). Hemorrhagic stroke occurrence was found to be associated with age and diabetes mellitus. Comparison on hemorrhagic stroke subtypes between study and matched cohorts showed no statistical differences in intracerebral hemorrhage and subarachnoid hemorrhage. Conclusions Despite the advancement of aneurysmal repair surgery, this study suggests that pTAA patients may still face an increased risk of hemorrhage stroke. Further investigation is warranted to provide better long-term care for the pTAA population.

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Long term clinical outcomes of patients with ischemic stroke in primary care – a 9-year retrospective study

BMC Family Practice ◽

10.1186/s12875-021-01513-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jinghao Han ◽

Yue Kwan Choi ◽

Wing Kit Leung ◽

Ming Tung Hui ◽

Maria Kwan Wa Leung

Keyword(s):

Blood Pressure ◽

Primary Care ◽

Risk Factor ◽

Ischemic Stroke ◽

Diastolic Blood Pressure ◽

Recurrent Stroke ◽

Stroke Patients ◽

All Cause Mortality

Abstract Background We aim to document the long-term outcomes of ischemic stroke patients and explore the potential risk factors for recurrent cardiovascular events and all-cause mortality in primary care. Methods A retrospective cohort study performed at two general out-patient clinics (GOPCs) under Hospital Authority (HA) in Hong Kong (HK). Ischemic stroke patients with at least two consecutive follow-up visits during the recruitment period (1/1–30/6/2010) were included. Patients were followed up regularly till the date of recurrent stroke, cardiovascular event, death or 31/12/2018. The primary outcome was the occurrence of recurrent cerebrovascular event including transient ischemic stroke (TIA), ischemic stroke or hemorrhagic stroke. The secondary outcomes were all-cause mortality and coronary artery disease (CAD). We fit cox proportional hazard model adjusting death as competing risk factor to estimate the cause-specific hazard ratio (csHR). Results A total of 466 patients (mean age, 71.5 years) were included. During a median follow-up period of 8.7 years, 158 patients (33.9%) died. Eighty patients (17.2%) had recurrent stroke and 57 (12.2%) patients developed CAD. Age was an independent risk factor for recurrent stroke, CAD and death. Statin therapy at baseline had a protective effect for recurrent stroke (csHR = 0.476; 95% confidence interval [CI] 0.285–0.796, P = 0.005) after adjusting death as a competing risk factor and all-cause mortality (HR = 0.693, 95% CI 0.486–0.968, P = 0.043). In addition, female sex, antiplatelet and a higher diastolic blood pressure (DBP) at baseline were also independent predictors for survival. Conclusions Long term prognosis of ischemic stroke patients in primary care is favorable. Use of statin was associated with a significant decrease in stroke recurrence and mortality. Patients who died had a significant lower DBP at baseline, highlighted the need to consider both systolic and diastolic blood pressure in our daily practice.

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WMH and long-term outcomes in ischemic stroke

Neurology ◽

10.1212/wnl.0000000000007142 ◽

2019 ◽

Vol 92 (12) ◽

pp. e1298-e1308 ◽

Cited By ~ 24

Author(s):

Marios K. Georgakis ◽

Marco Duering ◽

Joanna M. Wardlaw ◽

Martin Dichgans

Keyword(s):

Ischemic Stroke ◽

Functional Impairment ◽

Recurrent Stroke ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Stroke Recurrence ◽

Stroke Severity ◽

Stroke Patients ◽

Increased Risk

ObjectiveTo investigate the relationship between baseline white matter hyperintensities (WMH) in patients with ischemic stroke and long-term risk of dementia, functional impairment, recurrent stroke, and mortality.MethodsFollowing the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42018092857), we systematically searched Medline and Scopus for cohort studies of ischemic stroke patients examining whether MRI- or CT-assessed WMH at baseline are associated with dementia, functional impairment, recurrent stroke, and mortality at 3 months or later poststroke. We extracted data and evaluated study quality with the Newcastle–Ottawa scale. We pooled relative risks (RR) for the presence and severity of WMH using random-effects models.ResultsWe included 104 studies with 71,298 ischemic stroke patients. Moderate/severe WMH at baseline were associated with increased risk of dementia (RR 2.17, 95% confidence interval [CI] 1.72–2.73), cognitive impairment (RR 2.29, 95% CI 1.48–3.54), functional impairment (RR 2.21, 95% CI 1.83–2.67), any recurrent stroke (RR 1.65, 95% CI 1.36–2.01), recurrent ischemic stroke (RR 1.90, 95% CI 1.26–2.88), all-cause mortality (RR 1.72, 95% CI 1.47–2.01), and cardiovascular mortality (RR 2.02, 95% CI 1.44–2.83). The associations followed dose-response patterns for WMH severity and were consistent for both MRI- and CT-defined WMH. The results remained stable in sensitivity analyses adjusting for age, stroke severity, and cardiovascular risk factors, in analyses of studies scoring high in quality, and in analyses adjusted for publication bias.ConclusionsPresence and severity of WMH are associated with substantially increased risk of dementia, functional impairment, stroke recurrence, and mortality after ischemic stroke. WMH may aid clinical prognostication and the planning of future clinical trials.

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Long Term Clinical Outcomes of Patients with Ischemic Stroke in Primary care – A 9-year Retrospective Study

10.21203/rs.3.rs-42359/v1 ◽

2020 ◽

Author(s):

Jinghao Han ◽

Yue Kwan Choi ◽

Wing Kit Leung ◽

Eric Ming Tung Hui ◽

Maria Kwan Wa Leung

Keyword(s):

Blood Pressure ◽

Primary Care ◽

Ischemic Stroke ◽

Diastolic Blood Pressure ◽

Cardiovascular Events ◽

Recurrent Stroke ◽

Stroke Patients ◽

All Cause Mortality

Abstract Background: We aim to document the long-term outcomes of ischemic stroke patients and explore the potential risk factors for recurrent cardiovascular events and all-cause mortality in primary care.Methods: A retrospective cohort study performed at two general out-patient clinics (GOPCs) under Hospital Authority (HA) in Hong Kong (HK). Ischemic stroke patients with at least two consecutive follow-up visits during the recruitment period (1/1-30/6/2010) were enrolled. Patients were followed up regularly till the date of recurrent stroke, cardiovascular event, death or 31/12/2018. Risks of recurrent cardiovascular events and death were estimated by Cox proportional hazards model. The primary outcome was the occurrence of recurrent cerebrovascular event including transient ischemic stroke (TIA), ischemic stroke or hemorrhagic stroke. The secondary outcomes were all-cause mortality and coronary heart disease (CHD).Results: A total of 466 patients (mean age, 71.5 years) were enrolled. During a median follow-up period of 8.7 years, 158 patients (33.9%) died. Eighty patients (17.2%) had recurrent stroke and 57 (12.2%) patients developed CHD. Age was an independent risk factor for recurrent stroke, CHD and death. Statin therapy at baseline had a protective effect for recurrent stroke (hazard ratio [HR] =0.454, 95% confidence interval [CI] 0.269-0.766, P=0.003) and all-cause mortality (HR= 0.693, 95% CI 0.486-0.968, P=0.043). In addition, female sex, antiplatelet and a higher diastolic blood pressure (DBP) at baseline were also independent predictors for survival.Conclusions: Long term prognosis of ischemic stroke patients in primary care is favorable. Use of statin was associated with a significant decrease in stroke recurrence and mortality. Patients who died had a significant lower DBP at baseline, highlighted the need to consider both systolic and diastolic blood pressure in our daily practice.

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Abstract 63: Three-month Outcomes in Japanese Stroke /TIA Patients With Non-valvular Atrial Fibrillation After Initiating Oral Anticoagulants: The SAMURAI-NVAF Study

Stroke ◽

10.1161/str.46.suppl_1.63 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Shoji Arihiro ◽

Kenichi Todo ◽

Masatoshi Koga ◽

Hiroshi Yamagami ◽

Tadashi Terasaki ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Recurrent Stroke ◽

Oral Anticoagulants ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

Fatal Bleeding ◽

Index Stroke ◽

Ischemic Events

Backgound and Purpose: Recently, three non-vitamin K antagonist oral anticoagulants (NOACs) became available for patients with nonvalvular atrial fibrillation (NVAF) in Japan. We aimed to determine 3-month outcomes in ischemic stroke/TIA patients receiving NOACs or warfarin from a multicenter prospective registry (SAMURAI-NVAF registry, NCT01581502). Methods: Among 1,191 acute ischemic stroke /TIA patients enrolled between September 2011 and March 2014, we studied 916 patients (389 women, 77±10 y) who took oral anticoagulants (OACs) after index stroke and completed 3-month follow-up survey. Primary outcome measures were ischemic events, including recurrent stroke/TIA and thromboembolism, and major bleedings events, such as fatal bleeding and/or symptomatic bleeding in a critical area or organ according to the International Society on Thrombosis and Haemostasis statement. We assessed the incidence and clinical factors associated with primary outcomes within 90 days after initiating OACs. Results: NOACs were given for 370 patients (126 women, 74±9 y; dabigatran 168, rivaroxaban 183 and apixaban 19) and warfarin for 546 (263 women, 79±10 y). NOAC users had lower scores of CHADS2 (median 3 in NOAC, 4 in warfarin, p<0.001) and HAS-BLED (3, 3, p<0.001) than warfarin users. Ischemic events occurred in 14 NOAC users (3.8%; 2 women, 76±6 y, including 8 lower dose users between two approved dose for each NOAC) and 25 warfarin users (4.6%; 13 women, 81±9 y). Of these, 13 NOAC users (3.5%) and 16 warfarin users (2.9%) developed ischemic stroke/TIA. Among NOAC users, patients with ischemic events had lower body weights (53±11 vs 60±11kg, p= 0.017), more frequently had congestive heart failure (36 vs 10%, p = 0.003) and intracardiac thrombus (27 vs 4%, p < 0.001) than those without. Major bleeding events occurred in 5 NOAC users (1.4%, all using lower dose), and 14 warfarin users (2.6%). Of these, one NOAC user (0.3%) and 4 warfarin users (0.7%) developed intracranial hemorrhage. Conclusion: The 3-month incidence of ischemic events in stroke/TIA patients with NVAF was approximately 4% in both NOAC and warfarin users. Intracranial hemorrhage was relatively infrequent in NOAC users.

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Prior intracerebral hemorrhage and white matter hyperintensity burden on recurrent stroke risk

Scientific Reports ◽

10.1038/s41598-021-96809-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jong-Ho Park ◽

Sun U. Kwon ◽

Hyuk Sung Kwon ◽

Sung Hyuk Heo

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Intracerebral Hemorrhage ◽

Hemorrhagic Stroke ◽

Small Vessel Disease ◽

Recurrent Stroke ◽

White Matter Hyperintensity ◽

Major Adverse Cardiovascular Events ◽

Stroke Incidence ◽

Increased Risk

AbstractPrior intracerebral hemorrhage (ICH) is associated with increased risk of ischemic stroke. Since white matter hyperintensity (WMH) is associated with ischemic stroke and ICH, this study aimed to evaluate the relationship between ICH and the risk of recurrent stroke by WMH severity. From a prospective multicenter database comprising 1454 noncardioembolic stroke patients with cerebral small-vessel disease, patients were categorized by presence or absence of prior ICH and WMH severity: mild-moderate WMH (reference); advanced WMH; ICH with mild-moderate WMH; and ICH with advanced WMH. Among patients with ICH, the association with stroke outcomes by WMH burden was further assessed. The primary endpoint was ischemic stroke and hemorrhagic stroke. The secondary endpoint was major adverse cardiovascular events (MACE): stroke/coronary heart disease/vascular death. During the mean 1.9-year follow-up period, the ischemic stroke incidence rate per 100 person-years was 2.7, 4.0, 2.5, and 8.1 in increasing severity, and the rate of hemorrhagic stroke was 0.7, 1.3, 0.6, and 2.1, respectively. The risk of ischemic stroke was higher in ICH with advanced WMH (adjusted HR 2.62; 95% CI 1.22−5.60) than the reference group, while the risk of hemorrhagic stroke trended higher (3.75, 0.85–16.53). The risk of MACE showed a similar pattern in ICH with advanced WMH. Among ICH patients, compared with mild WMH, the risk of ischemic stroke trended to be higher in advanced WMH (HR 3.37; 95% CI 0.90‒12.61). Advanced WMH was independently associated with an increased risk of hemorrhagic stroke (HR 33.96; 95% CI 1.52−760.95). Given the fewer rate of hemorrhagic stroke, the risk of hemorrhagic stroke might not outweigh the benefits of antiplatelet therapy for secondary prevention.

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Long term exposure to ambient fine particulate matter and incidence of stroke: prospective cohort study from the China-PAR project

BMJ ◽

10.1136/bmj.l6720 ◽

2019 ◽

pp. l6720 ◽

Cited By ~ 15

Author(s):

Keyong Huang ◽

Fengchao Liang ◽

Xueli Yang ◽

Fangchao Liu ◽

Jianxin Li ◽

...

Keyword(s):

Cohort Study ◽

Ischemic Stroke ◽

Particulate Matter ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Hemorrhagic Stroke ◽

Fine Particulate Matter ◽

Fine Particulate ◽

Increased Risk

AbstractObjectiveTo study the effect of long term exposure to ambient fine particulate matter of diameter ≤2.5 μm (PM2.5) on the incidence of total, ischemic, and hemorrhagic stroke among Chinese adults.DesignPopulation based prospective cohort study.SettingPrediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project carried out in 15 provinces across China.Participants117 575 Chinese men and women without stroke at baseline in the China-PAR project.Main outcome measuresIncidence of total, ischemic, and hemorrhagic stroke.ResultsThe long term average PM2.5 level from 2000 to 2015 at participants’ residential addresses was 64.9 μg/m3, ranging from 31.2 μg/m3 to 97.0 μg/m3. During 900 214 person years of follow-up, 3540 cases of incident stroke were identified, of which 63.0% (n=2230) were ischemic and 27.5% (n=973) were hemorrhagic. Compared with the first quarter of exposure to PM2.5 (<54.5 μg/m3), participants in the highest quarter (>78.2 μg/m3) had an increased risk of incident stroke (hazard ratio 1.53, 95% confidence interval 1.34 to 1.74), ischemic stroke (1.82, 1.55 to 2.14), and hemorrhagic stroke (1.50, 1.16 to 1.93). For each increase of 10 μg/m3 in PM2.5 concentration, the increased risks of incident stroke, ischemic stroke, and hemorrhagic stroke were 13% (1.13, 1.09 to 1.17), 20% (1.20, 1.15 to 1.25), and 12% (1.12, 1.05 to 1.20), respectively. Almost linear exposure-response relations between long term exposure to PM2.5 and incident stroke, overall and by its subtypes, were observed.ConclusionsThis study provides evidence from China that long term exposure to ambient PM2.5 at relatively high concentrations is positively associated with incident stroke and its major subtypes. These findings are meaningful for both environmental and health policy development related to air pollution and stroke prevention, not only in China, but also in other low and middle income countries.

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Incidence of Bleeding in Patients with Sickle Cell Disease: A Population Based Study

Blood ◽

10.1182/blood-2018-99-114223 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 10-10

Author(s):

Nisha Hariharan ◽

Ann M Brunson ◽

Theresa H.M. Keegan ◽

Ted Wun

Keyword(s):

Ischemic Stroke ◽

Cumulative Incidence ◽

Hemorrhagic Stroke ◽

Severe Disease ◽

Bleeding Event ◽

Gi Bleeding ◽

Gross Hematuria ◽

Bleeding Events ◽

Risk Of Death ◽

Increased Risk

Abstract Background: Bleeding in patients with sickle cell disease (SCD) occurs at a number of sites, often with significant morbidity and mortality. The increased risk of hemorrhagic stroke, hematuria, and vitreous hemorrhage in SCD patients is well known. However, the overall cumulative incidence of both major and clinically relevant, non-major bleeding events in SCD patients has not been well-described. Therefore, we determined the cumulative incidence of and risk factors for bleeding amongst patients with SCD. We also determined the association between bleeding and overall mortality. Methods: We utilized the California Patient Discharge Dataset (PDD) and Emergency Department (ED) Dataset to identify patients with SCD between 1991-2014. We then used specific ICD-9 CM codes to identify the first admission (PDD or ED) for bleeding events: intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, hemophthalmos, gross hematuria, and "other" bleeding (including hemopericardium, pulmonary bleed, and hemarthrosis). The cumulative incidence of bleeding was adjusted for the competing risk of death using age as the time scale and stratified by disease severity (severe disease was defined as requiring an average of ≥ 3 hospitalizations or ED visits per year). Cox proportional hazards regression models were used to determine factors associated with bleeding (all, ICH and GI) and the association of bleeding with mortality. Models included age, race, SCD related complications (ischemic stroke, venous thromboembolism [VTE], osteonecrosis of the femoral head [ONFH], renal failure, and liver failure) and disease severity. Complications and bleeding were included as time-dependent covariates. Results: Of the 6,423 SCD patients identified, 15.9% had an index bleeding event. Of these, 65.6% were GI bleeding, 14.2% were ICH, 7.1% were hemophthalmos, 4.3% were gross hematuria, and 8.8% were other types of bleeding. The top six diagnoses of GI bleeding were GI hemorrhage not otherwise specified, melena, hematemesis, rectal and anal hemorrhage, chronic gastric ulcer with hemorrhage, and Mallory-Weiss syndrome. Figure 1 shows the cumulative incidence of bleeding overall and by bleeding type. The incidence of all bleeding was 15.5% (95% confidence interval (CI) 14.4 - 16.6) at age 40 years and 33.6% (CI 31.5 - 35.8%) at age 60. The incidence of bleeding was higher among SCD patients with severe disease. For example, the cumulative incidence of GI bleeding at age 40 was 15.8% (CI 14.2-17.4%) among severe SCD patients compared to 4.8% (CI 3.9-5.8%) for those with less severe disease. In multivariable models, a higher risk of all bleeding was associated with severe SCD, VTE within 180 days prior to bleeding event, ONFH, ischemic stroke, renal failure and liver failure (Table 1). In multivariable models by bleeding type, there was a strong association between VTE and ischemic stroke with risk of ICH. In addition, ONFH was positively associated with risk of GI bleed. Bleeding was associated with a two-fold increased risk of death (hazard ratio =2.28; CI 1.97-2.64), adjusted for other SCD related complications. Bleeding had a similar negative effect on mortality as other complications. Conclusion: The findings from our study indicate that SCD patients have a high cumulative incidence of bleeding. While the increased incidence of intracranial, urological, and retinal bleeding has been previously described and are confirmed here, we present the novel finding that SCD patients also have a high incidence of GI bleeding, the majority of which are from an upper GI source. The association of hemorrhagic stroke with a history of ischemic stroke is also confirmed. The association of bleeding with VTE is likely due, at least in part, to anticoagulation. Further studies on the causes and risk factors for GI bleeding in patients with SCD are warranted, and possibilities include gastritis from increased use of non-steroidal anti-inflammatory drugs (hence the association of ONFH with GI bleeding) and stress ulcerations from frequent hospitalizations. Such data could inform preventive strategies. Disclosures No relevant conflicts of interest to declare.

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