Abstract WP235: Risk of Arterial Ischemic Events After Non-Traumatic Subdural Hemorrhage

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Santosh B Murthy ◽  
Xian Wu ◽  
Ivan Diaz ◽  
Melvin Parasram ◽  
Neal S Parikh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antithrombotic Therapy ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Subdural Hemorrhage ◽  
Medicare Beneficiaries ◽  
Primary Analysis ◽  
Ischemic Event ◽  
Increased Risk ◽  
Ischemic Events

Introduction: To study the risk of arterial ischemic events after non-traumatic subdural hemorrhage (SDH). Methods: We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. The exposure was diagnosis of SDH. Our primary outcome was an arterial ischemic event defined as a composite of acute ischemic stroke and acute myocardial infarction (MI). Secondary outcomes were ischemic stroke alone and MI alone. We used validated ICD-9-CM diagnosis codes to identify our predictor and outcomes. We excluded patients who had an arterial ischemic event prior to SDH diagnosis. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio (HR) in each 4-week interval after discharge for SDH. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease and venous thromboembolism). Results: Among 1.7 million Medicare beneficiaries, 2,939 were diagnosed with SDH. Compared to patients without SDH, those with SDH were more often older, male, and had more vascular risk factors. In the 4 weeks after SDH, patients’ risk of an arterial ischemic event was substantially increased (HR, 4.2; 95% CI, 2.2-6.7). There was no association between SDH diagnosis and arterial ischemic event risk beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients’ risk of ischemic stroke was increased (HR, 5.6; 95% CI, 3.6-9.7) but not their risk of MI (HR, 0.8, 95% CI, 0.2-1.7). Patients with strong indications for antithrombotic therapy had similarly increased risks for arterial ischemic events as compared to patients in the primary analysis; patients without strong indications for antithrombotic did not demonstrate an increased risk for arterial ischemic events. Conclusions: Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events, particularly ischemic stroke, in the four weeks after SDH. This increased risk may be driven by withholding of antithrombotic therapy after SDH diagnosis.

scholarly journals Non-Traumatic Subdural Hemorrhage and Risk of Arterial Ischemic Events

Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1464-1469 ◽  
Author(s):  
Santosh B. Murthy ◽  
Xian Wu ◽  
Ivan Diaz ◽  
Melvin Parasram ◽  
Neal S. Parikh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Antithrombotic Therapy ◽  
Hazard Ratio ◽  
Subdural Hemorrhage ◽  
Medicare Beneficiaries ◽  
Ischemic Event ◽  
Increased Risk ◽  
Ischemic Events

Background and Purpose— The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods— We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries. The exposure was nontraumatic SDH. Our primary outcome was an arterial ischemic event, a composite of acute ischemic stroke and acute myocardial infarction. Secondary outcomes were ischemic stroke alone and myocardial infarction alone. We used validated International Classification of Diseases , Ninth Revision , Clinical Modification diagnosis codes to identify our predictor and outcomes. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio in 4-week intervals after SDH discharge. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease, and venous thromboembolism). Results— Among 1.7 million Medicare beneficiaries, 2939 were diagnosed with SDH. In the 4 weeks after SDH, patients’ risk of an arterial ischemic event was substantially increased (hazard ratio, 3.6 [95% CI, 1.9–5.5]). There was no association between SDH diagnosis and arterial ischemic events beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients’ risk of ischemic stroke was increased (hazard ratio, 4.2 [95% CI, 2.1–7.3]) but their risk of myocardial infarction was not (hazard ratio, 0.8 [95% CI, 0.2–1.7]). Patients with strong indications for antithrombotic therapy had increased risks for arterial ischemic events similar to patients in the primary analysis, but those without such indications did not demonstrate an increased risk for arterial ischemic events. Conclusions— Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events driven by an increased risk of ischemic stroke, in the 4 weeks after nontraumatic SDH. This increased risk may be due to interruption of antithrombotic therapy after SDH diagnosis.

Abstract P439: Mortality After an Arterial Ischemic Event Among Intracerebral Hemorrhage Survivors

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Melvin Parasram ◽  
Neal S Parikh ◽  
Alexander E Merkler ◽  
Guido J Falcone ◽  
Kevin N Sheth ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Confidence Interval ◽  
Intracerebral Hemorrhage ◽  
Medicare Beneficiaries ◽  
Ischemic Event ◽  
Risk Of Death ◽  
Diagnosis Codes ◽  
Increased Risk ◽  
Secondary Analyses ◽  
Ischemic Events

Background and Purpose: Emerging data suggest an increased risk of arterial ischemic events after intracerebral hemorrhage (ICH), but their impact on ICH outcomes is unclear. This study aimed to evaluate the risk of death among ICH survivors with and without an incident arterial ischemic event. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries with a non-traumatic ICH from January 2008 to October 2015. Our exposure was an arterial ischemic event, defined as a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was death. After excluding ischemic events and deaths in the first 30 days after ICH discharge to prevent carryover of diagnosis codes from the initial hospitalization, we used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for demographics and vascular comorbidities as time-varying covariates. In secondary analyses, we studied the mortality risk separately after an ischemic stroke and MI. Results: Among 8,222 Medicare beneficiaries with an ICH, 2,371 (28.8%) had an arterial ischemic event. During a median follow up time of 2.0 years (interquartile range, 0.8-3.8), the cumulative mortality rate was 7.0% (95% confidence interval [CI], 6.5-7.5%) in patients with an arterial ischemic event and 4.0% (95% CI, 3.8-4.2%) in patients without an arterial ischemic event. In the marginal structural model, the occurrence of an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.5- 1.7). In secondary analyses, the mortality risk was elevated after both an ischemic stroke (HR, 1.5; 95% CI, 1.4-1.6), and a MI (HR, 2.6; 95% CI, 2.1-3.2). Conclusions: In a large population-based cohort, we found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI. Careful exploration of secondary cardiovascular and stroke prevention strategies may be warranted in these patients.

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation

2020 ◽  
Vol 49 (6) ◽  
pp. 619-624
Author(s):  
Keisuke Tokunaga ◽  
Masatoshi Koga ◽  
Sohei Yoshimura ◽  
Yasushi Okada ◽  
Hiroshi Yamagami ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Transient Ischemic Attack ◽  
Left Atrial ◽  
Nonvalvular Atrial Fibrillation ◽  
Ischemic Event ◽  
Increased Risk ◽  
Ischemic Attack ◽  
Ischemic Events

<b><i>Background:</i></b> The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). <b><i>Methods:</i></b> Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. <b><i>Results:</i></b> A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9–2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02–3.00). <b><i>Conclusion:</i></b> Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

scholarly journals Long-Term Risk of Ischemic Stroke among Elderly Survivors of Non-Traumatic Subarachnoid Hemorrhage

2021 ◽  
pp. 1-6
Author(s):  
Melvin Parasram ◽  
Neal S. Parikh ◽  
Alexander E. Merkler ◽  
Judy H. Ch’ang ◽  
Babak B . Navi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Cox Regression ◽  
Sensitivity Analyses ◽  
Medicare Beneficiaries ◽  
Cox Models ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Traumatic Subarachnoid Hemorrhage

<b><i>Introduction:</i></b> Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood. <b><i>Objectives:</i></b> The aim of this study was to evaluate the risk of ischemic stroke among survivors of SAH. <b><i>Methods:</i></b> We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke, both identified using previously validated <i>ICD-9-CM</i> diagnosis codes. We used Cox regression analysis adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. <b><i>Results:</i></b> Among 1.7 million Medicare beneficiaries, 912 were hospitalized with non-traumatic SAH. During a median follow-up of 5.2 years (IQR, 2.7–6.7), the cumulative incidence of ischemic stroke was 22 per 1,000 patients per year among patients with SAH, and 7 per 1,000 patients per year in those without SAH. In adjusted Cox models, SAH was associated with an increased risk of ischemic stroke (HR, 2.0; 95% confidence interval, 1.4–2.8) as compared to beneficiaries without SAH. Similar results were obtained in sensitivity analyses, when treating death as a competing risk (sub HR, 3.0; 95% CI, 2.8–3.3) and after excluding ischemic stroke within 30 days of SAH discharge (HR, 1.5; 95% CI, 1.1–2.3). <b><i>Conclusions:</i></b> In a large, heterogeneous national cohort of elderly patients, survivors of SAH had double the long-term risk of ischemic stroke. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

Risk of Mortality After an Arterial Ischemic Event Among Intracerebral Hemorrhage Survivors

2021 ◽  
pp. 194187442110267
Author(s):  
Melvin Parasram ◽  
Neal S. Parikh ◽  
Alexander E. Merkler ◽  
Guido J. Falcone ◽  
Kevin N. Sheth ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Confidence Interval ◽  
Intracerebral Hemorrhage ◽  
Structural Model ◽  
Medicare Beneficiaries ◽  
Ischemic Event ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact ◽  
Time Varying Covariates

Background and Purpose: The impact of arterial ischemic events after intracerebral hemorrhage (ICH) on outcomes is unclear. This study aimed to evaluate the risk of death among ICH survivors with and without an incident arterial ischemic event. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries with a non-traumatic ICH from January 2008 to October 2015. Our exposure was an arterial ischemic event, a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was mortality. We used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for confounders as time-varying covariates. Results: Among 8,804 Medicare beneficiaries with ICH, 2,371 (26.9%) had an arterial ischemic event. During a median follow-up time of 1.9 years (interquartile range, 0.7-3.9), ICH patients with an arterial ischemic event had a mortality rate of 21.7 (95% confidence interval [CI], 20.4-23.0) per 100 person-years compared to a rate of 15.0 (95% CI, 14.4-15.6) per 100 person-years in those without. In the marginal structural model, an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.6-1.9). In secondary analyses, the mortality risk was elevated after an ischemic stroke (HR, 1.7; 95% CI, 1.5-1.8), and MI (HR, 3.0; 95% CI, 2.4-3.8). Conclusions: We found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI.

IL6 trans-signalling associates with atherothrombotic but not with cardioembolic stroke

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Ziegler ◽  
H Wallen ◽  
S Aspberg ◽  
U De Faire ◽  
B Gigante
Keyword(s):  
Ischemic Stroke ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Study Participant ◽  
Cardioembolic Stroke ◽  
Binary Complex ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Old Men ◽  
Study Participants

Abstract Background Pro-inflammatory processes underlie ischemic stroke, albeit it is largely unknown if they selectively associate with the risk of atherothrombotic and cardioembolic ischemic stroke. Here we analyse whether the pro-inflammatory interleukin (IL) 6 trans-signalling, associates with the risk of ischemic stroke and underlying atrial fibrillation (AF). Method During a 20-year follow-up, 203 incident ischemic strokes were recorded from national registers in the cohort of 60-year-old men and women from Stockholm (n=4232). For each study participant, we have estimated the activity of the IL6 trans-signalling through the calculation of the ratio between the circulating pro-inflammatory binary IL6:sIL6R complex and the circulating inactive ternary IL6:sIL6R:sgp130 complex, the so called B/T ratio. An excess of the binary complex, mirrored by a high B/T ratio, is associated with an increased risk of cardiovascular events. The B/T ratio has been dichotomized at the median. The risk of ischemic stroke associated with B/T ratio &gt; median was estimated by Cox regression and expressed as hazard ratio (HR) with a 95% confidence interval (CI) in the presence and absence of AF. Risk estimates were adjusted for cardiovascular risk factors and anticoagulant treatment. In a secondary analysis, the association of IL6 trans-signalling with the risk of incident AF (n=279) was analysed. Results B/T ratio &gt;median was associated with the risk of ischemic stroke only in study participants without AF diagnosis (adjusted HR 1.49; 95% CI 1.08–2.06). No association was observed with ischemic stroke in study participants also diagnosed with AF. Moreover, the B/T ratio was not associated with the risk of AF (HR 0.96; 95% CI 0.75–1.24). Conclusions IL6 trans-signalling, estimated by the B/T ratio, is associated with atherothrombotic but not cardioembolic stroke. Consistently, the B/T ratio did not associate with the risk of incident AF. Our results support the relevance of IL6 trans-signalling in atherosclerosis related ischemic stroke. Funding Acknowledgement Type of funding source: None

Abstract P628: Long-Term Risk of Ischemic Stroke Among Survivors of Non-Traumatic Subarachnoid Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Melvin Parasram ◽  
Neal S Parikh ◽  
Alexander E Merkler ◽  
Babak B Navi ◽  
Hooman Kamel ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Cox Regression ◽  
Medicare Beneficiaries ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Procedural Complication ◽  
National Cohort ◽  
Traumatic Subarachnoid Hemorrhage

Background and Purpose: Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008-2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke. The exposure and outcomes were identified using previously validated ICD-9-CM diagnosis codes. We excluded patients with prevalent ischemic stroke at the time of SAH diagnosis and those which occurred in the first 90 days after SAH discharge to avoid inclusion of stroke occurring as a medical or procedural complication of SAH. We used Cox regression adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. Results: Among 1.3 million Medicare beneficiaries, 3,171 (0.18%) were diagnosed with non-traumatic SAH. During a median follow-up of 5.3 years (interquartile range [IQR], 2.7- 6.7), the cumulative incidence of ischemic stroke was 92 per 1,000 patients per year among patients with SAH, and 21 per 1,000 patients per year in those without SAH. In multivariable Cox regression analysis, SAH was associated with an increased risk of ischemic stroke (hazard ratio, 2.6; 95% confidence interval, 2.4-2.8) as compared to beneficiaries without SAH. Conclusions: In a large, heterogeneous national cohort of elderly patients, we found that survivors of SAH had more than double the long-term risk of ischemic stroke as compared to those without SAH. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

scholarly journals IL6 trans-signaling associates with ischemic stroke but not with atrial fibrillation

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Louise Ziegler ◽  
Håkan Wallén ◽  
Sara Aspberg ◽  
Ulf de Faire ◽  
Bruna Gigante
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Men And Women ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Old Men ◽  
Study Participants

Abstract Background Pro-inflammatory processes underlie ischemic stroke, albeit it is largely unknown if they selectively associate with the risk of atherothrombotic or cardioembolic ischemic stroke. Here we analyze whether pro-inflammatory interleukin (IL) 6 trans-signaling, is associated with the risk of ischemic stroke and underlying atrial fibrillation (AF). Methods During a 20-year follow-up, 203 incident ischemic strokes were recorded from national registers in the cohort of 60-year-old men and women from Stockholm (n = 4232). The risk of ischemic stroke associated with circulating IL6 trans-signaling, assessed by a ratio between the pro-inflammatory binary IL6:sIL6R complex and the inactive ternary IL6:sIL6R:sgp130 complex (B/T ratio), was estimated by Cox regression and expressed as hazard ratio (HR) with a 95% confidence interval (CI) in the presence or absence of AF. Risk estimates were adjusted for cardiovascular risk factors and anticoagulant treatment. In a secondary analysis, the association of IL6 trans-signaling with the risk of incident AF (n = 279) was analyzed. Results B/T ratio > median was associated with increased risk of ischemic stroke in study participants without AF (adjusted HR 1.49; 95% CI 1.08–2.06), while an association could not be demonstrated in the presence of AF. Moreover, the B/T ratio was not associated with the risk of AF (HR 0.96; 95% CI 0.75–1.24). Conclusions Pro-inflammatory IL6 trans-signaling, estimated by the B/T ratio, is associated with ischemic stroke in individuals without AF. These findings suggest that the B/T ratio could be used to assess the risk of non-AF associated ischemic stroke.

New-onset type 2 diabetes in heart failure: impact of heart failure and death versus ischemic events – a Danish nationwide cohort study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Zareini ◽  
P.B Blanche ◽  
A.H Holt ◽  
M.M Malik ◽  
D.P Rajan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Risk Ratio ◽  
Real Life ◽  
Ischemic Event ◽  
Increased Risk ◽  
The Absolute ◽  
Ischemic Events ◽  
New Onset

Abstract Background Development of type 2 diabetes (T2D) is common in patients with heart failure (HF), but knowledge of future cardiovascular events is lacking. Purpose We compared risk of heart failure hospitalization (HFH) or death versus ischemic events in real-life HF patients with new-onset T2D, prevalent T2D and no T2D. Methods Using the Danish nationwide registers, we identified all patients with HF between 1998–2016. The patients were separated in two different HF cohorts based on the status of T2D. One cohort consisted of HF patients with either prevalent or absent T2D at the time of HF diagnosis. The other cohort consisted of HF patients, who developed new-onset T2D, included at time of diagnosis. The two HF cohorts were analyzed separately. Outcomes for both cohorts were analyzed as time-to-first event as either an ischemic event (i.e. composite outcome of fatal and non-fatal myocardial infarction, stroke, and peripheral artery disease), HFH, or event-free death (not related to HFH or the ischemic event). For each cohort, we estimated the five-year absolute risk of ischemic event, HFH and event-free death, along with five-year risk ratio of HFH or event-free death versus ischemic events. Effects among subgroups were investigated by stratifying both cohorts based on age, gender and comorbidities present at inclusion. Results A total of 139,264 HF patients were included between 1998 and 2016, of which 29,078 (21%) patients had prevalent T2D at baseline. A total of 11,819 (8%) developed new-onset T2D and were included in the second cohort. The median duration of time between HF diagnosis and new-onset T2D diagnosis was: 4.1 years (IQR:1.5; 5.8). The absolute five-year risk of an ischemic event in patients with new-onset T2D, prevalent T2D and no T2D was: 17.9% (95% confidence interval (CI): 17.2; 18.6), 26.1% (95% CI: 25.6; 26.7), and 18.8% (95% CI:18.6; 19.0). Corresponding estimates for HFH were: 31.5% (95% CI: 30.6; 32.3), 33.6% (95% CI: 33.0; 34.2), and 30,7% (95% CI: 30.5; 31.0). The absolute five-year risk of event-free death among patients with new-onset T2D, prevalent T2D and no T2D was: 20.9% (95% CI: 20.2; 21.7), 18.9% (95% CI:18.4; 19.3), and 18.6% (95% CI: 18.4; 18.8) (see Figure). The five-year risk ratio of experiencing HFH or event-free death versus an ischemic event was: 2.9 (95% CI: 2.8; 3.1), 2.0 (95% CI:2.0; 2.1), and 2.6 (95% CI: 2.6; 2.7) for patients with new-onset T2D, prevalent T2D and no T2D, respectively. Similar results of absolute and relative risk were present across all subgroups. Conclusion In our population of HF patients, 8% developed new-onset diabetes. Development of T2D in patients with HF increases the risk of HFH and mortality three-fold. The increased risk of new-onset T2D is higher than the importance of prevalent T2D in patients with HF. Funding Acknowledgement Type of funding source: None

071 Natalizumab extended interval dosing (EID) is associated with a significant reduction in progressive multifocal leukoencephalopathy (PML) risk compared with standard interval dosing (SID) in the touch® prescribing program

2018 ◽  
Vol 89 (6) ◽  
pp. A29.2-A29 ◽  
Author(s):  
Lana Zhovtis Ryerson ◽  
John Foley ◽  
Ih Chang ◽  
Ilya Kister ◽  
Gary Cutter ◽  
...  
Keyword(s):  
Cox Regression ◽  
Jc Virus ◽  
Secondary Analysis ◽  
Statistical Analysis Plan ◽  
Rank Test ◽  
Primary Analysis ◽  
Standard Interval ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Dosing Intervals

IntroductionNatalizumab, approved for 300 mg intravenous every-4-weeks dosing, is associated with PML risk. Prior studies have been inconclusive regarding EID’s impact on PML risk. The US REMS program (TOUCH) offers the largest data source that can inform on PML risk in patients on EID. This analysis aimed to determine whether natalizumab EID is associated with reduced PML risk compared with SID.MethodsInvestigators developed SID and EID definitions and finalised the statistical analysis plan while blinded to PML events. Average dosing intervals (ADIs) were ≥3 to<5 weeks for SID and >5 to≤12 weeks for EID. The primary analysis assessed ADI in the last 18 months of infusion history. The secondary analysis identified any prolonged period of EID at any time in the infusion history. The tertiary analysis assessed ADI over the full infusion history. Only anti-JC virus antibody positive (JCV Ab+) patients with dosing intervals≥3 to≤12 weeks were included. PML hazard ratios (HRs) were compared using adjusted Cox regression models and Kaplan-Meier estimates.ResultsAnalyses included 13,132 SID and 1988 EID patients (primary), 15,424 SID and 3331 EID patients (secondary), and 23,168 SID and 815 EID patients (tertiary). In primary analyses, ADI (days) was 30 for SID and 37 for EID; median exposure (months) was 44 for SID and 59 for EID. Most EID patients received >2 years SID prior to EID. The PML HR (95% CI) was 0.06 (0.01–0.22; p<0.001) for primary analysis and 0.12 (0.05–0.29; p<0.001) for secondary analysis (both in favour of EID); no EID PML cases were observed in tertiary analyses (Kaplan-Meier log-rank test p=0.02).ConclusionIn JCV Ab +patients, natalizumab EID is associated with a clinically and statistically significant reduction in PML risk as compared with SID. As TOUCH does not collect effectiveness data, further studies are needed.Study supportBiogen

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