Economic Evaluation of Andexanet Versus Prothrombin Complex Concentrate for Reversal of Factor Xa-Associated Intracranial Hemorrhage

 WHOM allows research into cost before telling us exactly how to 100% recover from this Intracranial Hemorrhage?  THIS is what is wrong with stroke, totally wrong focus of stroke research.  All because we have NO stroke strategy leading to 100% recovery, and that is because we have NO STROKE LEADERSHIP.

Economic Evaluation of Andexanet Versus Prothrombin Complex Concentrate for Reversal of Factor Xa-Associated Intracranial Hemorrhage

Andrew Micieli

,

Andrew M. Demchuk

,

Harindra C. Wijeysundera

Originally published1 Mar 2021https://doi.org/10.1161/STROKEAHA.120.031108Stroke. ;0

Abstract

Background and Purpose:

Andexanet was approved by the Food and Drug Administration in 2018 for reversal of life-threatening or uncontrolled bleeding associated with factor Xa anticoagulation; however, the cost-effectiveness of Andexanet compared with standard of care (ie, prothrombin complex concentrate, PCC) in patients with factor Xa–associated intracranial hemorrhage (ICrH) is unknown.

Methods:

Cost-effectiveness analysis using a Markov cohort decision analytic model with a lifetime horizon was completed to determine the costs and benefits of Andexanet compared with PCC for reversal of factor Xa–associated ICrH. The population of interest was patients living in Canada on chronic factor Xa inhibitors for prevention of ischemic stroke in nonvalvular atrial fibrillation or the prevention/treatment of venous thromboembolism, presenting with an ICrH. Outcomes of interest were life expectancy (measured in years), quality-adjusted life years (QALY), costs (reported in 2020 Canadian dollars), and the incremental cost-effectiveness ratio.

Results:

An overall reduction in fatal ICrH and increase in thromboembolic events was associated with Andexanet compared with PCC. Andexanet had the highest discounted life expectancy of 2.53 years and a discounted QALY of 1.55. PCC had a discounted life expectancy of 2.09 years and a discounted QALY of 1.28. The average discounted lifetime costs were $237 177 Canadian dollars for Andexanet and $177 871 Canadian dollars for PCC. The strategy of Andexanet had an incremental cost-effectiveness ratio was $219 652 per QALY gained compared with the comparator of PCC. The probabilistic sensitivity analyses demonstrated that Andexanet (at its current cost) was cost-effective in 19% of simulations using a willingness-to-pay threshold of $50 000/QALY and 33% of simulations at $150 000/QALY. A 1-way sensitivity analysis found that for the incremental cost-effectiveness ratio to be <$150 000/QALY gained, Andexanet high or standard dosing would require a price reduction to <$24 000 Canadian (at current baseline efficacy).

Conclusions:

Based on available evidence, Andexanet represents low value for reversal of factor Xa–associated ICrH; however, there is substantial uncertainty reflecting the currently available data. Further comparative evidence and costing data will become available in the future with randomized trials of Andexanet versus PCC.

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Can a hi-tech plaster stop fatal blood clots that cause strokes and heart attacks? A new patch 'turbocharges' the body's blood-thinning molecules, making its defences more effective

Pretty cool idea. Should be able to do INR testing this way also and deliver warfarin in the right dose
http://www.dailymail.co.uk/health/article-4026284/Can-hi-tech-plaster-stop-fatal-blood-clots-cause-strokes-heart-attacks-new-patch-turbocharges-body-s-blood-thinning-molecules-making-defences-effective.html

• Millions are already taking tablets containing heparin to reduce the risk of clots
• The new patch automatically injects the same drug through miniature needles
• This prevents patients from taking too much, which can cause fatal bleeding

A high-tech skin patch could prevent deadly blood clots that cause strokes and heart attacks.

The patch detects when a clot is in danger of developing and automatically releases a blood thinner into the bloodstream in time to stop it.

It does this through micro-needles in the patch which gently pierce tiny blood vessels — called capillaries — just beneath the skin.

As blood passes by, the needles — each one not much thicker than a human hair — monitor levels of thrombin, a clotting agent which increases in the blood when it is becoming dangerously thick and prone to clotting.

If thrombin levels are abnormally high, tiny amounts of a drug called heparin are released to thin the blood and reduce the clotting risk.

Heparin works by 'turbocharging' the body's own blood-thinning molecule, called antithrombin III, making it up to 2,000 times more effective.

Millions of people in Britain already take heparin tablets daily to reduce the risk of clots, or thrombosis.

Some are prescribed it because they have atrial fibrillation, an irregular heartbeat which can make blood pool inside the heart, increasing the chances of a clot breaking away and travelling to the brain — causing a stroke.

Others take the drug because they have already had a stroke and are at high risk of another.

Patients who have had major surgery — such as hip or knee replacement — are also put on short courses of heparin tablets or injections as immobility puts them at high risk of a clot because blood pools in their legs.

But those on drugs such as heparin need frequent blood tests to ensure they are getting exactly the right dose.

Too much medicine can cause potentially fatal bleeding, because blood is too thin to clot. Too little means they can still be in danger of a potentially lethal clot.

The postage stamp-sized patch, developed at North Carolina State University, keeps a round-the-clock check on thrombin levels and so does away with the need for repeated blood tests.

On one side it is covered in more than 100 miniature plastic needles. These are covered in a coating containing liquid heparin and a special chemical containing amino acids that binds the drug to the surface of the needles.

When thrombin levels are elavated, a chemical reaction takes place within the amino acid coating — and releases heparin into the blood. So far, the disposable patch, which can be changed daily, has only been tested on mice.

Scientists injected them with large amounts of thrombin — enough to cause a fatal blood clot — after giving them a patch or a heparin jab.

HIGHER RISK OF BLOOD CLOTS FOR THOSE TAKING TESTOSTERONE PILLS

The risk of blood clots increases in the first six months after starting testosterone therapy for erectile dysfunction, according to a report in the BMJ.

Researchers studied 19,000 patients who had developed blood clots and found that compared with men who hadn't used testosterone, current users had a 25 per cent higher risk. Why is unclear, but researchers say men should discuss it with doctors after starting testosterone treatment.

The results, published last month in the journal Advanced Materials, showed all the mice with the patch survived but 80 per cent of those on a heparin injection died from the results of a clot.

Researchers said early results suggest the patch is faster and more effective than injecting the drug, or taking it orally. The team now plan to run studies testing the patch on patients.

Professor Martin Cowie, a professor of cardiology at Imperial College London, says the smart patch could improve anticoagulation for patients at risk of clots.

'The concept of a self-regulating patch that tailors the release of a drug as needed into the body is very innovative. It's well worth pursuing,' he adds.

Professor Jeremy Pearson, an associate medical director at the British Heart Foundation, believes that the patch is 'an ingenious approach'.

'It may have advantages over current treatment which requires repeated injections of heparin,' he says. 'The initial results in mice show promise. It will be interesting to see whether these can be reproduced in human studies.' 

Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke - Japan

The failure could easily been because they were using invalid endpoints like the Rankin scale.
 The Rankin Scale has no useful discrimination at all. You should be using scans that show dead and damaged areas. 

Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke - Japan

Observational Nationwide Study in Japan

1. Tomoki Wada, MD;
2. Hideo Yasunaga, MD, PhD;
3. Hiromasa Horiguchi, PhD;
4. Takehiro Matsubara, MD, PhD;
5. Kiyohide Fushimi, MD, PhD;
6. Susumu Nakajima, MD, PhD;
7. Naoki Yahagi, MD, PhD

+ Author Affiliations

1. From the Departments of Emergency and Critical Care Medicine (T.W., T.M., S.N., N.Y.) and Clinical Epidemiology and Health Economics, School of Public Health (H.Y.), The University of Tokyo, Tokyo, Japan; Department of Clinical Data Management and Research, Clinical Research Center, National Hospital Organization Headquarters, Tokyo, Japan (H.H.); and Department of Health Policy and Informatics, Tokyo Medical and Dental University, Tokyo, Japan (K.F.).

1. Correspondence to Tomoki Wada, MD, Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail wadat-eme@h.u-tokyo.ac.jp

Abstract

Background and Purpose—Argatroban, a selective thrombin inhibitor, is recommended for the use in patients with atherothrombotic stroke by the Japanese Guidelines for the Management of Patients with Acute Ischemic Stroke. We performed a nationwide Japanese study to investigate whether argatroban improved early stroke outcomes in patients with acute atherothrombotic stroke.

Methods—This retrospective observational study, using the Diagnosis Procedure Combination database in Japan, included patients who were hospitalized from July 1, 2010, to March 31, 2012, with a diagnosis of atherothrombotic stroke within 1 day of stroke onset. Patients were divided into 2 groups: those receiving argatroban on admission (argatroban group), and those who did not receive argatroban during hospitalization (control group). To balance the baseline characteristics and concomitant treatments during hospitalization between the 2 groups, one-to-one propensity-score matching analyses were performed. The main outcomes were the modified Rankin Scale score at discharge and the occurrence of hemorrhagic complications during hospitalization. An ordinal logistic regression analysis evaluated the association between argatroban use and modified Rankin Scale at discharge.

Results—After propensity-score matching, 2289 pairs of patients were analyzed. There were no significant differences in modified Rankin Scale at discharge between the argatroban and the control groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.88–1.16). The occurrence of hemorrhagic complications did not differ significantly between the argatroban and the control groups (3.5% versus 3.8%; P=0.58).

Conclusions—The present study suggested that argatroban was safe, but had no added benefit in early outcomes after acute atherothrombotic stroke.

Nanotechnology urine test could detect deadly blood clots

So who is going to translate this into  a actual test usable in doctor offices and hospitals?  Damnable lazy stroke associations, you know who you are. Why don't you ever write on survivor blogs telling us what you are doing for survivors?

Nanotechnology urine test could detect deadly blood clots

The abstract this is based on here;

Nanoparticles That Sense Thrombin Activity As Synthetic Urinary Biomarkers of Thrombosis

Thrombin is a serine protease and regulator of hemostasis that plays a critical role in the formation of obstructive blood clots, or thrombosis, that is a life-threatening condition associated with numerous diseases such as atherosclerosis and stroke. ... Using a thromboplastin-induced mouse model of pulmonary embolism, we show that urinary biomarker levels differentiate between healthy and thrombotic states and correlate closely with the aggregate burden of clots formed in the lungs. ... Here we hypothesized that synthetic biomarkers could be tailored to survey intravascular sites for acute thrombosis, the activation of a cascade of protease activity that orchestrates the formation of obstructive blood clots within vessels (Figure 1A)

Minor Trauma Led to Death in Pradaxa Patient

A friend of mine was on Pradaxa for a while and she was extremely concerned about bleeding and the lack of a reversal agent.
http://www.medpagetoday.com/Neurology/HeadTrauma/31524?utm_source=cardiodaily&utm_medium=email&utm_content=aha&utm_campaign=03-07-12&eun=gd3r&userid=424561&email=oc1dean@yahoo.com&mu_id=
A dabigatran (Pradaxa) patient's death from a brain hemorrhage following a fall has again highlighted concerns over lack of an effective reversal agent for the drug.
Despite treatment with recombinant factor VII, the 83-year-old man deteriorated rapidly as the bleeding spread across most of the left hemisphere of his brain in just six hours, according to Richard H. Schmidt, MD, PhD, of the University of Utah in Salt Lake City, and colleagues.
"Imbalance and falls are common in this population, and intracranial hemorrhage resulting even from minor trauma may occur with increasing frequency as use of this drug becomes more widespread," they warned in a case report published online in the Journal of Neurosurgery.
A high index of suspicion for catastrophic hemorrhage in dabigatran users is critical so that what limited management options there are can be started without delay, the group urged.
The direct thrombin inhibitor acts at the very end of the coagulation cascade, so factor VIIa and fresh-frozen plasma don't work. Prothrombin complex concentrate hasn't been tested outside of animal models yet.
Dialysis can remove 35% to 60% of circulating dabigatran in two to three hours, but wasn't considered until too late to be effective for the reported case.
The group recommended checking the thrombin time and starting dialysis early along with judicious IV fluids to maintain renal perfusion, which is the main route of dabigatran excretion.
"Caution is necessary, however, because patients with atrial fibrillation have tenuous intravascular volume status, and fluid overload can lead to worsening heart function," they warned in the paper.
Hematologists expressed similar concerns over lack of reversibility in a recent review of a cluster of bleeding episodes in New Zealand, largely involving older patients and those with impaired renal function.
The drug was widely hailed initially for its ability to be given at a fixed dose without the need for frequent adjustments and monitoring.
In the pivotal RE-LY trial, bleeding risks were similar to those with warfarin. But since FDA approval in 2010 for stroke prevention in atrial fibrillation, reports have surfaced of a possible excess of bleeding deaths with the drug, prompting an ongoing safety review by the FDA.
Drugmaker Boehringer Ingelheim has called these reports within what would be expected based on the clinical trial, noting that dabigatran's prescribing information cites a trend for higher major bleed rates with the 150-mg dose versus warfarin in the 75-and-older population.
In the case report, the 83-year-old man had been on 150-mg twice-daily dabigatran for new-onset atrial fibrillation for one month before the ground-level fall at home that sent him to the emergency department.
On arrival, the man was alert and responsive with a normal neurological exam and a Glasgow Coma Scale score of 15. The initial CT scan showed only small, superficial areas of hemorrhage in his right temporal lobe and left temporal and parietal lobes.
Within two hours, he developed slurred speech and his neurological state began to deteriorate rapidly. Repeat CT imaging showed significant progression of right parenchymal and left frontal hemorrhages.
The neurosurgical team members knew they had limited options to reverse the blood thinner, which had left the patient with an international normalized ratio of 1.4 and a thrombin time over 150 seconds compared with the normal 15 to 20 seconds.
Despite trying a weight-based dose of recombinant factor VII for its rapid onset of action, mental status continued to slide to the point where the man lapsed into a coma (Glasgow Coma Scale score 6) and required emergency endotracheal intubation.
His final CT scan six hours after admission showed hemorrhage encompassing most of the left hemisphere and effacing the left lateral ventricle.
The patient was transitioned to palliative care after extensive discussion with his family and died shortly thereafter.
Dabigatran is only the first in a class of direct thrombin inhibitors that may raise these problems, Schmidt's group noted.
Others are on the horizon, "and these agents will likely have similar risks for catastrophic progression of traumatic injuries," they warned.

Thrombin Activity Associated with Neuronal Damage during Acute Stage of Ischemic Stroke

A new hyperacute damage finding.
http://www.eurekalert.org/pub_releases/2012-02/cmc-ais013112.php
After ischemic stroke – the type caused by a clogged artery but with no bleeding into the brain – a normal protein that plays a positive role in blood clotting escapes intact arteries and seriously damages healthy brain cells. Scientists previously knew that thrombin leaked out during hemorrhagic strokes, and large amounts of the protein killed neurons. In new studies, researchers found thrombin in the brain after ischemic stroke; injecting a drug to counter the effects of thrombin improved stroke symptoms. Patrick D. Lyden, MD, chair of the Department of Neurology, the Carmen and Louis Warschaw Chair in Neurology at Cedars-Sinai and senior author of the poster presentation abstract, is available for interviews.