Drug taken for common condition may be slowing Alzheimer’s decline

 With your risk of dementia post stroke, is your competent? doctor preparing testing for stroke patients to see if this would prevent Alzheimers'? NO? NOTHING DOING? PURE INCOMPETENCE THEN!

Your risk of dementia, has your doctor told you of this?  Your doctor is responsible for preventing this! Is s/he willing to prevent this?

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

The latest here: 

Drug taken for common condition may be slowing Alzheimer’s decline

A blood-thinning medication already taken by millions of people for an irregular heartbeat may also be helping to slow cognitive decline in patients with Alzheimer’s disease, according to new research from Karolinska Institutet in Sweden.

The study, published in the European Heart Journal, found that people with both atrial fibrillation and Alzheimer’s disease who were treated with newer blood thinners known as NOACs unintentionally experienced a significantly slower rate of cognitive decline than those given the older drug named warfarin or no blood thinner at all.

“There are reasons to believe that the treatment could have a positive effect on cognition, for example by improving blood flow and reducing small-scale damage in the brain,” Maria Eriksdotter, a professor at Karolinska Institutet who led the study, said in a statement.

Newsweek reached out to Karolinska Institutet for more information.

Why the Two Conditions Are Often Linked

Atrial fibrillation, a common heart rhythm disorder among older adults, frequently occurs alongside Alzheimer’s disease.

Doctors typically prescribe blood-thinning medication to atrial fibrillation patients to lower their risk of blood clots. Earlier research had suggested that anticoagulant treatment might reduce the risk of developing dementia in the first place, but scientists knew far less about how these drugs affect people who already have Alzheimer’s.

Researchers drew on data from SveDem, Sweden’s national quality register for cognitive disorders and dementia, examining 7,308 people diagnosed with both atrial fibrillation and Alzheimer’s disease.

Participants were sorted into three matched groups: those taking NOACs, those taking warfarin, and those taking no anticoagulant medication at all. Cognitive function was tracked over time using the Mini-Mental State Examination (MMSE), a standard test used to measure memory and thinking skills.

What the Results Showed

Patients on NOACs saw their cognitive decline slow by just over 0.2 MMSE points per year compared with those on warfarin or no treatment at all.

The benefits extended beyond cognition. Patients treated with NOACs also had a lower risk of death, stroke, blood clots and fractures compared with those who received no anticoagulant treatment. Warfarin was also linked to lower risks of death, stroke and blood clots, but it came with a higher risk of major bleeding than NOACs.

England-based general practitioner, Dr Mohammad Bakhtiar, spoke with Newsweek about the findings.

“Over 7,000 people is large enough that the signal is hard to dismiss as noise,” he said. “That makes the data more reliable than the usual small clinic series.

“What I take from the study is encouraging evidence for the newer anticoagulants over warfarin in this group. The cognitive difference is modest, but it sits alongside fewer strokes, clots and deaths, and less major bleeding than warfarin. For GPs deciding between a NOAC and warfarin in someone with Alzheimer’s and atrial fibrillation, that is useful.”

The researchers cautioned that, because the study was observational, it cannot prove that the drugs directly caused the slower decline. Some factors that may have influenced both which drug a patient was prescribed and their eventual health outcomes could not be fully accounted for. Some patients also may have switched between medications during the course of the study, which followed participants over time. All in all, while they remain optimistic, they acknowledge the promising results require further studies.

“We should read observational studies cautiously,” Bakhtiar added. “People who get a NOAC are often different from people who get nothing. They may be fitter, better supported, or under more active specialist care. Some patients also switched drugs during follow-up.

“So, the honest line is association, not proof. NOACs were linked with slower decline. We do not know they caused it.”

He advises that patients excited by the news do not start, stop or switch their current medications because of this paper.

The study was funded by several organizations, including the Swedish Research Council, the Swedish Brain Foundation, CIMED, ALF project funding and Karolinska Institutet.

Reference

Eriksdotter, M., et al. (2026). Oral anticoagulants, cognition, and clinical outcomes in atrial fibrillation and Alzheimer’s disease: a Swedish nationwide study. European Heart Journal. https://doi.org/10.1093/eurheartj/ehag584.

Contact Newsweek editors on this story: Marc Vargas and Gray R. Thomas

Another NOAC Flops for Prevention After Cryptogenic Stroke Head-to-head trial with aspirin yielded no fewer recurrent strokes

So why is your doctor prescribing something that costs hundreds of dollars instead of cheap aspirin?

Another NOAC Flops for Prevention After Cryptogenic Stroke - Head-to-head trial with aspirin yielded no fewer recurrent strokes

• by Nicole Lou, Contributing Writer, MedPage Today May 16, 2019

Dabigatran (Pradaxa) was no better than aspirin for secondary stroke prevention in non-lacunar cryptogenic strokes, the RE-SPECT ESUS trial showed.
Recurrent stroke rates came out similar for patients with a recent history of embolic stroke of undetermined source randomized to the non-vitamin K antagonist oral anticoagulant (NOAC) as for those on placebo (4.1% vs 4.8% per year, HR 0.85, 95% CI 0.69-1.03).
The same was observed for ischemic strokes (4.0% vs 4.7% per year, HR 0.84, 95% CI 0.68-1.03), reported researchers led by Hans-Christoph Diener, MD, PhD, of University Hospital Essen in Germany.
Whereas major bleeding was similarly likely between groups (1.7% vs 1.4% per year, HR 1.19, 95% CI 0.85-1.66), there were more clinically-relevant non-major bleeds with dabigatran (1.6% vs 0.9% per year, HR 1.73, 95% CI 1.17-2.54).
Data from the trial's 19-month follow-up were published in the May 16 issue of the New England Journal of Medicine. Preliminary report of the results came out at the World Stroke Congress in 2018.
"Post hoc analysis suggested that dabigatran may have had an effect on stroke recurrence after 1 year, but no inferences can be made because of the post hoc nature of the analysis. A possible explanation for this temporal pattern might be a progressive increase in the occurrence of asymptomatic, undetected atrial fibrillation [Afib] and other cardiac sources of embolism over time," Diener and colleagues noted.
Another NOAC, rivaroxaban (Xarelto), was also shown to be no better than aspirin in preventing recurrent strokes in a similar population in NAVIGATE ESUS.
The 5,390 adults randomized in RE-SPECT ESUS received either dabigatran (150 mg or 110 mg twice daily depending on age and kidney function) or aspirin (100 mg once daily).
Study participants had had non-lacunar ischemic strokes -- with less than 50% stenosis in arteries supplying the territory, as well as no Afib lasting more than 6 minutes or any other identifiable source of emboli -- in the 3 to 6 months prior to enrollment.
Mean age was 64.2 years, and 36.9% of the cohort were women.
Trial investigators reported similar baseline characteristics between groups, except the dabigatran group was 0.6 years older on average.
"In our trial, extended ECG monitoring after randomization was performed in only 14% of patients; therefore, we do not have a systematic assessment of the occurrence of atrial fibrillation," Diener's group acknowledged.
That said, the strengths of RE-SPECT ESUS included its large sample size and sufficient stroke events to match expectations from the power calculation for the trial, according to the investigators.

The study was supported by Boehringer Ingelheim.
Diener reported receiving honoraria from Abbott, Allergan, Bayer Vital, Bristol-Myers Squibb, BrainsGate, CoAxia, Corimmun, Covidien, Daiichi Sankyo, D-Pharm, EV3, Fresenius, Knoll, Merck Sharpe & Dohme, Lilly, Medtronic, Mind-Frame, Neurobiological Technologies, Novo Nordisk, Paion, Parke-Davis, Pfizer, Schering-Plough, Servier, Solvay, ThromboGenics, and Wyeth; grant support and honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen-Cilag, Novartis, and Sanofi Aventis; and grant support from Lundbeck, Synagis, and Talecris.

last updated 05.16.2019

• Primary Source

  New England Journal of Medicine

  Source Reference: Diener HC, et al "Dabigatran for prevention of stroke after embolic stroke of undetermined source" New Engl J Med 2019; DOI: 10.1056/NEJMoa1813959.

Intravenous tPA (Tissue-Type Plasminogen Activator) in Patients With Acute Ischemic Stroke Taking Non–Vitamin K Antagonist Oral Anticoagulants Preceding Stroke

So not only do you have to have the perfect stroke symptoms to get diagnosed correctly, you have to not have a pre-existing disability and you shouldn't be taking a NOAC(dabigatran, etc.) Welcome to the real world of not knowing whether you will even be treated for your stroke. 

 

Intravenous tPA (Tissue-Type Plasminogen Activator) in Patients With Acute Ischemic Stroke Taking Non–Vitamin K Antagonist Oral Anticoagulants Preceding Stroke

Chen Jin

,

Ryan J. Huang

,

Eric D. Peterson

,

Daniel T. Laskowitz

,

Adrian F. Hernandez

,

Jerome J. Federspiel

,

Lee H. Schwamm

,

Deepak L. Bhatt

,

Eric E. Smith

,

Gregg C. Fonarow

, and

Ying Xian

Originally published9 Aug 2018Stroke. 2018;49:2237–2240

Abstract

Background and Purpose—

Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non–vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke.

Methods—

A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized.

Results—

We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5–14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0–2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12–2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08–1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45–14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death.

Conclusions—

These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.

NOAC Not Better Against Cryptogenic Stroke Recurrence

What is your doctor keeping you on after your stroke to prevent the next one?
https://www.medpagetoday.com/cardiology/strokes/72909?

Rivaroxaban had no advantage over aspirin, and increased bleeding risk in trial

• by Crystal Phend, Senior Associate Editor, MedPage Today May 16, 2018
• This article is a collaboration between MedPage Today® and:
  

Rivaroxaban (Xarelto) was not better than aspirin for preventing recurrence of ischemic strokes without a known source of the emboli, but it did increase bleeding risk, the NAVIGATE ESUS trial found.
For the primary endpoint, the non-vitamin K antagonist oral anticoagulant (NOAC) had an annualized rate of first recurrence of ischemic or hemorrhagic stroke or systemic embolism of 5.1% compared with 4.8% for aspirin (HR 1.07; 95% CI 0.87-1.33, P=0.52).
Recurrent ischemic stroke occurred at an identical 4.7% per year in both groups, Robert Hart, MD, of the Population Health Research Institute in Hamilton, Ontario, and colleagues reported online in the New England Journal of Medicine in a study published simultaneously with presentation at the European Stroke Organisation Conference in Gothenburg, Sweden.
Rivaroxaban substantially increased major bleeding, though, at an annualized rate of 1.8% compared with 0.7% on aspirin (HR 2.72, 95% CI 1.68-4.39, P<0.001). Life-threatening or fatal bleeding (HR 2.34), symptomatic intracranial hemorrhage (HR 4.02), and clinically relevant nonmajor bleeding (HR 1.51) were also significantly worse with rivaroxaban.
The trial included 7,213 patients ages 50 and older with "embolic stroke of undetermined source" -- i.e., not associated with proximal arterial stenosis or a recognized cardioembolic source, such as atrial fibrillation or left ventricular thrombus, and that are not lacunar -- who were randomized to 15-mg immediate-release rivaroxaban or 100-mg aspirin enteric coated tablets along with placebo given both groups to maintain blinding.
All participants had at least 20 total hours of cardiac rhythm monitoring to rule out atrial fibrillation lasting 6 minutes or longer.
"Rivaroxaban, including the 15-mg daily dose that was used in the current trial, has been effective for the prevention of recurrent stroke in patients with atrial fibrillation," the researchers noted, "and the absence of an observed lower rate of recurrent ischemic stroke with rivaroxaban than with aspirin in the current trial suggests that undetected paroxysmal atrial fibrillation was not a major cause of recurrent stroke."
While 7% of the included patients had a patent foramen ovale, the outcome influence of including these patients "is uncertain," according to the researchers, noting that the trials showing a benefit to closure in cryptogenic stroke came out just when recruitment stopped in NAVIGATE ESUS.
The trial was stopped early for excess bleeding risk without an offsetting chance of stroke prevention efficacy after patients had been followed for a median 11 months and 74% of the planned efficacy events had occurred.
Using a 20 mg rather than 15 mg dose of rivaroxaban wouldn't likely have made any difference in the findings, Hart's group suggested. But they noted that ongoing randomized trials are comparing other NOACs with aspirin in secondary prevention after cryptogenic stroke, such as RE-SPECT ESUS with dabigatran (Pradaxa) and ATTICUS with apixaban (Eliquis).

The trial was funded by Bayer and Janssen Research and Development.
Hart reported grants and personal fees from Bayer, outside of the NAVIGATE ESUS study.

• Primary Source

  New England Journal of Medicine

  Source Reference: Hart RG, et al "Rivaroxaban for stroke prevention after embolic stroke of undetermined source" N Engl J Med 2018; DOI: 10.1056/NEJMoa1802686.

Combining newer anticoagulants with some other drugs may be risky

Ask your doctor if they have taken this into account for your anticoagulant needs. Since I'm on atorvastatin I'll have to remind my doctor of this if I ever need NOACs.
https://www.mdlinx.com/family-medicine/top-medical-news/article/2017/10/04/7470762?

Reuters Health News

Combining several commonly prescribed medications with non-vitamin K oral anticoagulants (NOACs) may increase the risk of major bleeding in patients with nonvalvular atrial fibrillation (AF), suggest results of an observational study from Taiwan.
“Physicians should consider the potential risks associated with the concurrent use of NOACs and other drugs,” Dr. Shang-Hung Chang from Chang Gung Memorial Hospital in Taoyuan told Reuters Health by email. In particular, “combining fluconazole with NOACs looks risky based on the findings.
Physicians shall choose alternative whenever possible,” Dr. Chang said.
NOACs are increasingly being used instead of warfarin because of their ease of administration and comparable efficacy in patients with AF. However, they often are prescribed with other medications that share metabolic pathways that may increase the risk of bleeding.
To investigate, Dr. Chang and colleagues analyzed data from the Taiwan National Health Insurance database on 91,330 adults with nonvalvular AF who received at least one NOAC prescription (dabigatran, rivaroxaban, or apixaban).
They estimated the risk of major bleeding associated with or without the concurrent use of medications that share metabolic pathways with NOACs: atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; and phenytoin.
During the 5-year study period (from 2012 through 2016), there were 4,770 major bleeding events, defined as hospitalization or ED visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding.
Diltiazem and amiodarone were among the most common medications co-prescribed with a NOAC, despite guidance against their combined use, the authors note. Atorvastatin and digoxin were the other two most commonly co-prescribed medications.
According to the study team, the risk of major bleeding was significantly higher when a NOAC was combined with amiodarone, fluconazole, rifampin, or phenytoin rather than with a NOAC alone.
Adjusted incidence rates per 1,000 person-years were 38 for NOAC use alone versus 52 with concurrent use of amiodarone; corresponding rates were 103 versus 242 with fluconazole, 66 versus 103 for rifampin, and 56 vs 109 for phenytoin (P < 0.01 for all comparisons).
The other combinations did not confer increased risk of major bleeding, while atorvastatin, digoxin and erythromycin or clarithromycin were associated with a reduced risk of major bleeding.
To the authors' knowledge, this is the first nationwide population-based study to gauge the risk of major bleeding associated with a drug-drug interaction with NOACs.
They note that because the bleeding risk and anticoagulant treatment in the Asian population may differ from that of Western populations, the findings may not generalize to the West. The analyses also did not consider dosages of NOACs and the other medications, and kidney and liver function data were not available.

Improving Patient Outcomes in Preventing Atrial Fibrillation-related Stroke with Non-Vitamin K Antagonist Oral Anticoagulants

You might want to read if you have atrial fibrillation, unless you think your doctor will tell you this in the next two weeks.
http://www.touchneurology.com/articles/improving-patient-outcomes-preventing-atrial-fibrillation-related-stroke-non-vitamin-k

Peter Kelly, Carlos Molina, Christian T. Ruff, Roland Veltkamp

European Neurological Review, 2016;11(1):27–35 DOI: http://doi.org/10.17925/ENR.2016.11.01.1a

Abstract:

The rising incidence of atrial fibrillation (AF) is increasingly resulting in a substantial worldwide increase in AF-related stroke, particularly in elderly patients and this is creating an increasingly serious healthcare burden. Guidelines recommend the use of AF-related stroke prophylaxis but adherence to these remains poor. Studies conducted in the 1990s showed that warfarin reduced the risk of AF-related stroke by an overall 64% compared with placebo. Subsequently, prophylactic treatment was further improved with the development of non-vitamin K antagonist oral anticoagulants (NOACs). More recently, a meta-analysis of four large clinical trials on NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) showed there was a relative risk reduction of 0.81 (p<0.0001) favouring NOAC treatment over warfarin for stroke or systemic embolic events in patients with AF. The largest trial of NOACs in AF-related stroke, to date, was the ENGAGE AF-TIMI 48 study (n=21,105) which showed that edoxaban was non-inferior to warfarin for ischaemic stroke reduction but significantly reduced bleeding and cardiovascular mortality. A recent subgroup analysis of this study showed that with edoxaban the incidences of intracranial haemorrhage (ICH) subtypes (all ICH, fatal ICH, fatal, subdural and epidural bleed) were significantly lower with 60 mg of edoxaban (p=0.013–<0.001). Edoxaban was also shown to be an effective option in patients with prior stroke. In addition edoxaban was shown to reduce deaths due to fatal bleeds compared with warfarin. The results of current studies, especially the ENGAGE AF-TIMI 48 subgroup analysis therefore, show that the benefits of anticoagulation therapy in patients with AF substantially outweigh the risks

Keywords: Atrial fibrillation-related stroke, outcomes, non-vitamin K oral anticoagulants (NOACs)

Disclosure: Peter Kelly has served on advisory boards or received speakers fees or benefits from the American Stroke Association, Bayer and Daiichi Sankyo, and has received research unit grants from the Health Research Board of Ireland, Irish Heart Foundation and Bayer. Carlos Molina has nothing to declare in relation to this article. Christian T. Ruff has received research support from GlaxoSmithKline, Daiichi Sankyo, Intarcia and AstraZeneca, and serves as a consultant and on the advisory boards for Boehringer Ingelheim, Bayer, Daiichi Sankyo, Portola and DrugDev. Roland Veltkamp has received speaker fees, consulting honoraria and research support from Bayer, Boehringer Ingelheim, BMS, Pfizer, Daiichi Sankyo, CSL Behring, Apoplex Medical Technologies, Morphosys, Biogen, Medtronic.

Acknowledgments: Editorial assistance was provided by James Gilbart at Touch Medical Media, London, this was supported by an unrestricted grant from Daiichi Sankyo Europe GmbH. This article reports the proceedings of a sponsored satellite symposium and as such has not been subject to the journal’s usual peer-review process

Received: October 16, 2015 Accepted February 19, 2016

Correspondence: Peter Kelly, Stroke Service and NeuroVascular Unit for Translational and Therapeutics Research, University College Dublin, Ireland E: pjkelly@mater.ie.

Support: The publication of this article was supported by Daiichi Sankyo Europe GmbH. The views and opinions expressed are those of the authors and not necessarily those of Daiichi Sankyo Europe GmbH.

Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit

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In atrial fibrillation (AF), considerable harm can result from the lack of appropriate preventive therapy, and optimal prevention is critical, especially in vulnerable elderly or frail patients. AF markedly increases the risk of stroke and this condition must be monitored and potentially treated wherever it is detected.^1–4 AF is an increasing concern for physicians worldwide as populations age and more people are at risk.^5–7 Although guidelines for stroke prevention in AF that recommend anticoagulation have been established for many years, many at-risk patients receive inadequate anticoagulation or none at all.^8–11 This ‘reluctance to treat’ stems largely from a fear of inducing intracranial haemorrhage (ICH) and other serious bleeding types that are associated with warfarin and the non–vitamin K antagonist oral anticoagulants (NOACs). This risk, however, is often over-stated and substantially less than the risks that are associated with the lack of stroke prevention treatment in AF. This review discusses the burden of AF-related stroke and evidence that supports current treatments, and considers novel insights on the use of edoxaban as provided by recent subgroup analyses of the ENGAGE AF-TIMI 48 trial results (see end of article for trial name definitions). These topics were presented at a satellite symposium convened at the European Stroke Organisation Annual Meeting in Glasgow, UK, in April 2015.
Preventing the Rise of AF-related Stroke– A Call to Action
Large-scale population-based observational studies have shown AF to be a serious factor increasing the likelihood of strokes and substantially worsening mortality and morbidity after a stroke.¹² Various studies have predicted increasing incidence and prevalence of AF-related stroke and the associated heavy burden this will place on healthcare authorities worldwide. Professor Peter Kelly assessed the history and rising incidence of AF-related stroke. His message constitutes a call to action, encouraging physicians to treat all patients with AF to help stem the burgeoning number of ischaemic strokes and reduce the burden strokes impose on healthcare services.

7 more pages at link.

Patent - METHODS FOR TREATING INFLAMMATION

This one is so general that it would patent the use of aspirin/NOACs to combat inflammation.
http://www.freepatentsonline.com/y2015/0335739.html

Title:

METHODS FOR TREATING INFLAMMATION

Document Type and Number:

United States Patent Application 20150335739

Kind Code:

A1

Abstract:

The invention provides methods and compositions for inhibiting, reducing or slowing inflammation or inflammatory diseases, for reducing sequestration or collecting or localization of macrophages, for treating a disease caused all or in part by or characterized by inflammation such as, for instance, chronic inflammation, for inhibiting, slowing, reversing or preventing atherosclerosis, and for increasing insulin sensitivity, decreasing or inhibiting resistance to insulin, or treating diabetes by inhibiting, inhibiting the biological activity of or antagonizing an axonal guidance protein. The methods may feature administering to a subject a therapeutically effective amount of an agent effective to inhibit or reduce the biological activity of an axonal guidance protein or a receptor of the axonal guidance protein, or an analog, derivative or combination thereof. The disease may be, for instance, one of atherosclerosis, rheumatoid arthritis, tuberculosis, autoimmune syndromes and obesity where macrophage accumulation in adipose tissue is known to promote insulin resistance.

Abstract 17392: Gastrointestinal Bleeding With Edoxaban versus Warfarin: Results From the ENGAGE AF-TIMI 48 Trial

Be careful out there.
http://circ.ahajournals.org/content/132/Suppl_3/A17392.short

1. James Aisenberg1;
2. Kathryn Friedman1;
3. Jay Desai1;
4. Jeffrey I Weitz2;
5. Robert Giugliano3;
6. Christian T Ruff3;
7. Francesco Nordio3;
8. Michele Mercuri4;
9. Youngsook Choi4;
10. Laura Bower5;
11. Elliot Antman3;
12. Eugene Braunwald3

+ Author Affiliations

1. ¹Internal Medicine, Icahn Sch of Medicine, Mount Sinai Med Cntr, New York, NY
2. ²Internal Medicine, McMaster Univ and Thrombosis and Atherosclerosis Rsch Institute, Hamilton, Canada
3. ³TIMI Study Group, Div of Cardiovascular Medicine, Brigham and Women’s Hosp and Harvard Med Sch, Boston, MA
4. ⁴Pharma Development, Daiichi Sankyo, Edison, NJ
5. ⁵Pharma Development, Daiichi Sankyo, New York, NY

Abstract

Background: There is more major gastrointestinal bleeding (M-GIB) with most NOACs than with warfarin. The clinical impact of this finding is poorly understood.

Methods: The ENGAGE AF-TIMI 48 trial compared the efficacy and safety of higher-dose (HD-E: 60 mg/ 30mg) or lower-dose (LD-E: 30 mg/15 mg) edoxaban regimens with dose-adjusted warfarin for prevention of stroke and systemic embolism in non-valvular atrial fibrillation. ISTH definitions for major and life-threatening (LT) bleeding events were utilized. In this pre-specified analysis, we investigated the adjudicated M-GIB events utilizing pre-defined severity and outcome endpoints.

Results: Although the risk of M-GIB was higher with HD-E than with warfarin, the risk of LT or fatal GIB was similar (figure), and surgery for GIB was required less frequently with HD-E than warfarin (HR 0.37; 95%CI, 0.16-0.88; p=0.03). The risk for M-GIB-related permanent drug discontinuation was similar with HD-E and warfarin (HR 0.96; 95% CI, 0.67-1.37, p=0.8), as were the risks of hospitalization (HR 1.14; 95%CI, 0.92-1.40, p=0.2) and Hgb decrease > 5 g/dL (HR 1.01; 95%CI, 0.74-1.38; p=0.9). The risks of M-GIB and of LT or fatal GIB were lower with LD-E than with warfarin (Figure), as were the risks of M-GIB-related permanent drug discontinuation (HR 0.51; 95% CI, 0.33-0.78, p=0.002), hospitalization (HR 0.67; 95%CI, 0.53-0.85; p=0.001), Hgb decrease > 5 g/dL (HR 0.58; 95%CI, 0.40-0.84; p=0.003), and M-GIB requiring transfusion of > 2 units of red cells (HR 0.66; 95%CI, 0.50-0.89; p=0.006). Fatal GIB occurred in 2, 3 and 7 patients treated with HD-E, LD-E and warfarin, respectively.

Conclusions: M-GIB and LT-GIB with edoxaban are dose-dependent. Although the risk of M-GIB is higher with HD-E than warfarin, the risk of LT-GIB or fatal GIB is similar and the severity and outcomes are no worse than with warfarin. The risks of M-GIB, and of LT-GIB or fatal GIB, are lower with LD-E than warfarin.