Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 34,264 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Andexanet alfa (Andexxa) will officially be taken off the U.S. market this month as an emergency reversal medication for contemporary blood thinners. "The Biologics License Application for Andexxa has been withdrawn for commercial reasons, effective December 22, 2025," a spokesperson from drugmaker AstraZeneca said in an email to MedPage Today To some, it may come as no surprise that andexanet is leaving the market, as the pricey direct oral anticoagulant (DOAC) antidote had been rejected for traditional FDA approval last year. "In discussions with the FDA, alignment on a feasible path to convert Andexxa from accelerated to traditional approval in the U.S. could not be reached," AstraZeneca noted. "As agreed with the FDA, Andexxa will no longer be commercially sold by AstraZeneca in the U.S. after December 22, 2025." In May 2018, andexanet was granted accelerated approval as the sole antidote on the market for the DOACs rivaroxaban (Xarelto) or apixaban (Eliquis). It official indication
was the reversal of anticoagulation due to life-threatening or uncontrolled bleeding among patients treated with these factor Xa inhibitors.
Approval was based an interim ANNEXA-4 analysis of the first 227 patients recruited who had developed acute major bleeding while on apixaban and rivaroxaban. In the full report of ANNEXA-4, one bolus of andexanet indeed resulted in a drastic drop in median anti-factor Xa activity: from 149.7 ng/mL to 11.1 ng/mL among apixaban users, and from 211.8 ng/mL to 14.2 ng/mL for the rivaroxaban cohort.
Andexanet also showed efficacy controlling hematoma volume change at 12 hours based on the ANNEXA-I trial of DOAC users with intracerebral hemorrhage.
Safety concerns arose as early as 2016's ANNEXA-4 initial study presentation, however, when outside observers noted a signal of excess thrombotic events among the study's andexanet users. The clotting issue became more apparent with ANNEXA-I showing more thrombotic events (14.6% vs 6.9%) and more thrombosis-related deaths (2.5% vs 0.9%) comparing andexanet versus usual care with a prothrombin complex concentrate (PCC).
A critical FDA advisory committee ensued, during which agency advisors discussed their reservations about which dose and in which patients andexanet could safely be used to stop bleeding.
Following andexanet's withdrawal, PCC remains available as the antidote for acquired coagulation factor deficiency in people on anticoagulation -- albeit specifically for vitamin K antagonist therapy such as warfarin.
So until this Thromboelastography test exists and is a well documented protocol you can wait 48 hours after your last DOAC injestion before you get tPA. Hope you don't mind killing off billions of neurons. Just maybe you'll need to direct your doctor to use mechanical thrombectomy instead of waiting. Hope you are conscious enough to do that. Of course the simplest solution would be for you to lie and say you haven't taken any DOACs recently so you could get tPA immediately. This means this test would need to be available in the ambulance so you can get your tPA shot in the ambulance, waiting till hospital kills off way too many neurons.
Clinical conundrum could be solved by a point-of-care DOAC test
by
Nicole Lou, Staff Writer, MedPage Today
March 15, 2021
Current guidance on how to manage stroke patients on
direct oral anticoagulant (DOAC) therapy isn't right, but there aren't
the validated tools needed to do better either, lamented clinicians.
DOACs taken for stroke prevention may turn out to be the very reason for withholding treatment in acute stroke: guidelines
from the American Heart Association and American Stroke Association
have a class III recommendation against thrombolysis within 48 hours of
last DOAC intake for fear of bleeding.
"We
strongly disagree with this generalized recommendation," wrote a group
led by David Seiffge, MD, of the University Hospital of Bern,
Switzerland, in one of two viewpoint articles published online in JAMA Neurology.
"Available data show that carefully selected patients taking prior
DOAC therapy have similar bleeding risks to patients not taking DOAC
after IV thrombolysis," they argued.
Rather than categorically excluding DOAC users from recanalization
therapies, stroke treatment could incorporate selection of patients for
thrombolysis based on drug-specific assays (e.g., thromboelastography)
and use of reversal agents before thrombolysis (e.g., idarucizumab
[Praxbind] reversal of dabigatran [Pradaxa], andexanet alfa [Andexxa] reversal of factor Xa inhibitors) if necessary, Seiffge and colleagues suggested.
Thromboelastography shows promise for point-of-care testing, as it
measures viscoelastic properties of clotting blood and correlates with
serum DOAC levels. However, selection for thrombolysis using this method
has yet to be reported, and it needs to be more broadly available in
the first place.
"Why
are anti-Xa activity assays not more available? A strong call for
further validation and more availability of these tests should be a
priority, rather than a recommendation to fly by the seat of our pants,
so to speak, by giving a reversal agent and hoping for the best," wrote
Alexandra Czap, MD, of the University of Texas Health Science Center,
and James Grotta, MD, of Memorial Hermann Hospital-Texas Medical Center,
both in Houston, in another JAMA Neurology viewpoint piece.
The strategy of anticoagulant reversal before IV thrombolysis also suffers from the lack of data beyond observational reports.
Reversal agents are not all equal, either, as andexanet alfa as
compared with idarucizumab provides "much less reliable and durable
reversal at a much higher cost for the most commonly used DOACs,"
according to Czap and Grotta.
"[H]aving a point-of-care test available in the prehospital setting
or emergency department would make all the difference in being sure that
the patient needs the reversal agent and it has been successful in
reversing DOAC activity," the pair wrote.
Both
published viewpoints alluded to the low likelihood of convincing
randomized data coming out to assess DOAC reversal strategies before
stroke thrombolysis.
Seiffge's group raised another clinical conundrum: whether to offer bridging thrombolysis before endovascular thrombectomy among DOAC users in acute ischemic stroke.
This decision "should depend on several clinical factors including
rapid access to an endovascular center and the type of DOAC the patient
is taking," the group said.
"In summary, the decision of how to treat a patient having an acute
ischemic stroke while taking a DOAC is among the most complex and
nuanced in acute stroke management. Uncertainty regarding time between
the last DOAC dose and symptom onset and DOAC activity factor into risk
of bleeding, risk of clotting, and chance of benefit from the use of a
reversal agent prior to a thrombolytic agent," according to Czap and
Grotta.
"A point-of-care test would go a long way to help clinicians with
these areas of uncertainty, and development of such a test should be a
priority. In the meantime, cases need to be carefully individualized and
optimally managed by stroke specialists," the duo concluded.
Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow
This article is a collaboration between MedPage Today® and:
In a
real-world analysis involving more than 11,000 patients with atrial
fibrillation from 47 countries, the risk for stroke and major bleeding
in users of the direct oral anticoagulant rivaroxaban (Xarelto) was
similar to or lower than that seen in the pivotal clinical trials,
researchers report.
The one-year rate of stroke or systemic embolism was only 1.0% and
the rate of major bleeding was 1.7% in the large, pre-planned pooled
analysis of three previously described prospective, observational,
international, non-interventional studies that comprised the XANTUS
program.
"Overall,
rivaroxaban showed a favorable safety profile, with greater than 96% of
the pooled rivaroxaban population not experiencing any of the events of
treatment-emergent major bleeding, stroke/non-CNS systemic embolism
(SE) or all-cause death over a follow-up period of approximately one
year," wrote Paulus Kirchhof, MD, of the University of Birmingham in
England, and colleagues in the Journal of the American College of Cardiology, published online July 2.
The researchers noted that the XANTUS program offers a unique source
of real-world data on the use of rivaroxaban for stroke prevention in
Afib patients. The three prospective studies included patients from
Western and Eastern Europe, Canada and Israel (XANTUS trial), the
Asia-Pacific region (XANAP trial), and Eastern Europe the Middle East,
Africa and Latin America (XANTUS-EL).
Patients were prescribed the direct oral anticoagulant (DOAC) rivaroxaban in accordance with country-specific drug approvals.
Primary outcomes were treatment-emergent major bleeding, adverse
events (AEs)/serious AEs, and all-cause death. Secondary outcomes
included treatment-emergent thromboembolic events and non-major
bleeding.
Overall, 11,121 patients were included in the analysis (mean age
70.5±10.5 years; female 42.9%). Comorbidities included heart failure
(21.2%), hypertension (76.2%), and diabetes (22.3%).
Event rates, calculated as one event per 100 patient-years, were:
Major bleeding: 1.7/100 patient-years; 95% CI 1.5-2.0)
All-cause death: 1.9/100 patient-years (95% CI 1.6-2.2)
Stroke or systemic embolism: 1.0/100 patient-years (95% CI 0.8 to 1.2)
Regional differences were considerable. For instance, major bleeding
rates varied from 0.7 per 100 patient-years in Latin America verses 2.3
per 100 patient-years in a group including Western Europe, Canada, and
Israel.
One-year treatment persistence was 77.4%, with East Asia showing the lowest rate (66.4%) and Eastern Europe the highest (84.4%).
The researchers concluded that the real-world treatment analysis
showed low bleeding and stroke rates in rivaroxaban-treated patients
with Afib. Low rates of treatment discontinuation were seen throughout
the world and results were broadly consistent across regions.
Study limitations cited by the researchers included the exclusion of
patients from the United States and China (with the exception of Hong
Kong) from the analysis and possible selection bias, given that patients
had to agree to participate in the study.
In
an accompanying editorial, cardiologist Jeff Healey, MD, of McMaster
University in Hamilton, Ontario, noted that the study population was
very representative of the practices they came from.
"The age and the proportion of patients with hypertension, diabetes and prior stroke in this cohort are quite similar to another multinational registry enrolling
patients from the emergency department, suggesting that these patients
are reasonably representative of the larger population of individuals
with AF," he wrote. "Thus, like may observational studies, the current
study population is a reasonable balance of what is practical and what
is ideal."
Kirchhof and colleagues noted that the patients included in the
observational studies had similar characteristics to those included in
the clinical trials.
Healey wrote that the analysis confirms that "the use of rivaroxaban
is largely in accordance with published guidelines, and persistence with
therapy at one year was high, at least in the practices of
participating physicians."
"Although these data are not population-based, they represent what a
typical clinician might expect if they utilize a DOAC medication in
accordance with local product labeling and practice guidelines, and are a
testament to the successful introduction of DOACs into the clinical
practice," Healey wrote.
"Although the current work does not help us to understand why the
translation into clinical practice was so successful, easy-to-use
medications, clear high-quality randomized trials, thoughtful practice
guidelines, and coordinated physician education all likely played a
role."
The XANTUS resarch program was funded by Bayer.
Paulus
Kirchhof has received research support from Bayer HealthCare,
AstraZeneca, Bioscnece Webster, Boehringer Ingelheim and other
pharmaceutical companies.
The FDA approved the 10 mg once-daily dose of rivaroxaban (Xarelto) for patients who have taken at least 6 months of anticoagulation, manufacturer Janssen announced.
Approval was based on the EINSTEIN CHOICE study in which both 20-mg and 10-mg doses of rivaroxaban beat aspirin in reducing a patient's risk of recurrent venous thromboembolism (VTE) -- by 66% and 74%, respectively -- without an elevated bleeding risk.
The 3,396-patient trial was presented as a late-breaker at the American College of Cardiology meeting this year. "This is a useful and safe clinical pathway for managing these patients," the presenter said at the time. There is "really no role for aspirin in this setting ... I hope these findings will encourage more physicians to prescribe rivaroxaban for these patients."
Rivaroxaban is to be prescribed at 15 mg twice daily in the first 21 days after a VTE occurrence, followed by 20 mg once daily up to the 6-month mark. With this new approval, physicians can then start patients on a 10 mg once-daily regimen if they are at continued risk for deep vein thrombosis and pulmonary embolism.
Recurrent VTE is a quality marker used by Medicare.
Didn't answer the outstanding question that there is no reversal agent for the newer ones. How many died or had negative outcomes because of no reversal agent? Can't these people even think of the correct questions to answer while doing research? Must I do everything? Think and wipe their ass?
An observational study comparing new oral anticoagulants with
warfarin found stroke prevention to be similar, but the newer
anticoagulants provided reduced intracranial bleeding, according to a
study presented here at the 2016 Annual Meeting of the European Society
of Cardiology (ESC).
The study included 43,299 patients with atrial fibrillation who were
recruited from Danish nationwide administrative registries. In the
cohort, 42% of patients were taking warfarin, 29% were taking
dabigatran, 16% were on apixaban, and 13% were taking rivaroxaban.
“There has been a need to investigate safety and effectiveness of new
oral anticoagulants versus warfarin in a ‘real world’ population and
our Danish registries provide this opportunity,” said Laila Staerk, MD,
Herlev and Gentofte University Hospitals, Herlev, Denmark.
Efficacy outcomes were stroke and all-cause mortality. Patients were
followed until outcome, death, switch or discontinuation of initiated
anticoagulant treatment, emigration, or study end.
During treatment, stroke occurred in 1,850 (4%) patients and there were 6,477 (15%) deaths.
The absolute stroke risk at 1 year of initiating treatment was
similar for each of the 4 groups, at 2.01% for warfarin, 2.12% for
dabigatran, 2.06% for rivaroxaban, and 2.46% for apixaban.
Absolute risk of all-cause mortality at 1 year after initiation of
warfarin was 18.0%, dabigatran 11.5%, rivaroxaban 14.7%, and apixaban
14.9%.
Standardised absolute risk of intracranial bleeding at 1 year was
reduced in patients who were taking the newer oral anticoagulants.
Absolute risk was 0.60% for warfarin, 0.26% for dabigatran (P =0.05 vs
warfarin), 0.47% for rivaroxaban, and 0.40% for apixaban (P = .05 vs
warfarin).
“Among patients with atrial fibrillation who were new users of oral
anticoagulation, while treatment with [these newer drugs] was not
associated with a significantly lower risk of stroke, treatment with
dabigatran and apixaban was associated with a significantly lower risk
of intracranial bleeding compared with warfarin,” said Dr. Staerk.
[Presentation title: Stroke and All-Cause Mortality With Non-Vitamin K
Antagonist Oral Anticoagulation Versus Warfarin in Atrial Fibrillation:
a Nationwide Study. Abstract 1875]
So we are still going after the secondary issue in atherosclerosis, cholesterol, instead of finding out how to stop the inflammation in your arteries which is the real problem. I would be really concerned about reversing the effects of this. Does this cross the blood brain barrier?
Vaccine is cheaper and appears to be more effective than alternative treatments
A new cholesterol-lowering vaccine leads to reductions in 'bad' LDL
cholesterol in mice and macaques, according to research published in
Vaccine. The authors of the study, from the University of New Mexico and
the National Institutes of health in the United States, say the vaccine
has the potential to be a more powerful treatment than statins alone.
The
body produces cholesterol to make vitamin D, some hormones and some of
the molecules that help us digest food. Cholesterol is also found in
foods. LDL cholesterol is a fat-like substance that circulates in the
blood; if there is too much cholesterol, the arteries can become
blocked, leading to heart disease and stroke.
According to the
CDC, 73.5 million adults in the United States have high LDL cholesterol.
Diet and exercise are key to keeping cholesterol down, but millions of
people worldwide take statins to lower their cholesterol. Statins have
some potentially serious side effects, such as muscle pain, an increased
risk of diabetes and cognitive loss.
The new vaccine could
provide an alternative to statins, by targeting a protein that controls
cholesterol levels in the blood. A single vaccine has been shown to
reduce cholesterol levels dramatically in mice and macaques, suggesting
it could be an effective treatment in humans.
"One of the most
exiting things about this new vaccine is it seems to be much more
effective than statins alone," said Dr. Bryce Chackerian, one of the
authors of the study from the University of New Mexico.
The new
vaccine targets a protein called PCSK9, which regulates the cholesterol
in the blood. The protein works by encouraging the body to break down
receptors that cholesterol binds to when it's flushed out of the body.
People who have a mutation in the protein often suffer from increased
risk of heart disease, and people who do not produce the protein have a
decreased risk. By targeting this protein, the vaccine can stop it from
functioning, lowering the amount of cholesterol in the blood.
The
researchers tested the vaccine in mice, which showed a reduced level of
LDL cholesterol. They then tested it in a small group of macaques,
along with statins, resulting in a dramatic decrease in cholesterol.
"Statins
are still the most commonly prescribed medication for cholesterol.
Although they are effective in many people, do have side effects and
don't work for everyone," said Dr. Alan Remaley, one of the authors of
the study from the National Heart, Lung and Blood Institute, National
Institutes of Health. "The results of our vaccine were very striking,
and suggest it could be a powerful new treatment for high cholesterol."
Several
drug companies have been developing high cholesterol treatments that
target PCSK9 - for example, Alirocumab and Evolocumab, which the FDA
recently approved. Results have been positive, but their treatments,
which use monoclonal antibodies, are prohibitively expensive; treatment
costs upwards of $10,000 per year.
The new vaccine appears to be
even more effective than these monoclonal antibody-based treatments, at a
fraction of the cost. The researchers now plan to expand their studies
in macaques and find commercial partners to move the technology forward.
Read more about the study on Elsevier Connect: https://www.elsevier.com/connect/new-cholesterol-lowering-vaccine-could-help-tackle-heart-disease Full bibliographic informationArticle details "A
cholesterol-lowering VLP vaccine that targets PCSK9" by Erin Crossey,
Marcelo J..A. Amar, Maureen Sampson, Julianne Peabody, John T. Schiller,
Bryce Chackerian and Alan T. Remaley (doi:
10.1016/j.vaccine.2015.09.044). The article appears in Vaccine, Volume
33 (October 2015), published by Elsevier.
Idarucizumab instantly and completely reversed the anticoagulant effect of dabigatran in patients requiring urgent procedures or with serious hematologic complications, according to interim results of a phase 3 study.
Few specific reversal agents exist for non-vitamin K oral anticoagulants, according to study background. Researchers developed idarucizumab (Boehringer Ingelheim) to reverse the anticoagulant effects of dabigatran (Pradaxa, Boehringer Ingelheim).
Charles V. Pollack, Jr., MD, chair of the department of emergency medicine at Pennsylvania Hospital and professor of emergency medicine at the Hospital of the University of Pennsylvania, and colleagues conducted the prospective, phase 3 RE-VERSE AD study to observe the safety and efficacy of idarucizumab in reversing the effects of dabigatran.
Pollack and colleagues divided the study into two arms: patients experiencing severe bleeding (group A) and patients who required an urgent procedure (group B).
The researchers assigned 5 mg IV idarucizumab to patients in both groups.
The maximum percentage reversal of the anticoagulant effect of dabigatran — evaluated with the dilute thrombin time or ecarin clotting time — within 4 hours of idarucizumab administration served as the primary endpoint. Restoration of hemostasis served as a secondary endpoint.
The interim analysis included data from 90 patients (group A, n = 51; group B, n = 39).
At baseline, 68 patients had an elevated dilute thrombin time and 81 had an elevated ecarin clotting time. The study achieved its primary endpoint, with 100% of these patients (95% CI, 100-100) reaching maximum percentage reversal following idarucizumab administration.
Idarucizumab normalized the dilute thrombin time in 98% of patients in group A and 93% in group B, as well as the ecarin clotting time in 89% of patients in group A and 88% of patients in group B. In most cases, researchers observed these effects within minutes of administration.
Concentrations of unbound dabigatran stayed below 20 ng/mL in 79% of patients after 24 hours.
The researchers assessed hemostasis in 35 patients in group A and 36 patients in group B. Among patients in group A, hemostasis restoration occurred at a median of 11.4 hours. Thirty-three patients in group B who underwent a procedure experienced normal intraoperative hemostasis, whereas two patients experienced mildly abnormal hemostasis and one patient experienced moderately abnormal hemostasis.
A total of 18 patients died (n = 9 for each arm). Ten patients died from vascular causes, with five deaths attributed to bleeding events. Eleven patients died within 96 hours of treatment; however, their deaths appeared to be related to their index event.
Five patients experienced thrombotic events, including deep vein thrombosis and pulmonary embolism in one patient within 72 hours of idarucizumab administration.
Twenty-one patients (group A, n = 13; group B, n = 8) experienced serious adverse events, including gastrointestinal hemorrhage (n = 2), postoperative wound infection, delirium, right ventricular failure and pulmonary edema (n = 1 for all).
The researchers identified the lack of a control group as a limitation of their study.
“The interim analysis from RE-VERSE AD is important for the healthcare professionals as it provides the first insights into the effect of a specific reversal agent to a non–vitamin K antagonist oral anticoagulant during real-word emergency situations,” Pollack said in a press release. “These data demonstrate that use of idarucizumab can help physicians focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.” – by Cameron Kelsall
Idarucizumab restored clotting in most patients on the new oral
anticoagulant (NOAC) dabigatran (Pradaxa) who had serious bleeding or
required urgent surgery, according to interim results of the phase III RE-VERSE AD trial.
The median maximum percentage reversal of the anticoagulant effect of
dabigatran within 4 hours of administration was 100%, based on central
laboratory analysis of dilute thrombin time or ecarin clotting time.
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"Idarucizumab normalized the test results in 88% to 98% of the patients, an effect that was evident within minutes," Charles V. Pollack Jr., MD, of the Pennsylvania Hospital in Philadelphia, and colleagues found.
Be careful out there on those Warfarin replacements. Has your doctor told you all the side effects of Warfarin vs. Pradaxa? Don't listen to me, if your doctor doesn't tell you about these problems s/he must not consider them worthwhile or even worse does not know about the problems.
A good friend of mine refused to go on Pradaxa because of the lack of a reversal agent. https://us-mg5.mail.yahoo.com/neo/launch?.rand=5gfa04d2d1oug#4477885065
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