Tuesday, January 30, 2007
warfarin en aspirin
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Arch Intern Med. 1999 Jun 28;159(12):1322-8. Related Articles, Links 
Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation.
Gullov AL, Koefoed BG, Petersen P.
Department of Rheumatology, Glostrup University Hospital, Denmark.
BACKGROUND: Treatment with warfarin sodium is effective for stroke prevention in atrial fibrillation but many physicians hesitate to prescribe it to elderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients. METHODS: In the Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation (AFASAK 2) Study, we studied the rate of bleeding events associated with the incidence of thromboembolic events in patients receiving warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; aspirin, 300 mg/d; or adjusted-dose warfarin therapy aiming at an international normalized ratio of the prothrombin time ratio (INR) of 2.0 to 3.0. The study was scheduled for 6 years from May 1, 1993, but owing to evidence of inefficiency of low-intensity therapy plus aspirin from another study it was prematurely terminated on October 2, 1996. Minor and major bleeding events were recorded prospectively. The rate of bleeding was calculated using the Kaplan-Meier method and risk factors were identified by the Cox proportional hazards model. RESULTS: Of 677 included patients, 130 (median age, 77 years; range, 67-89 years) experienced bleeding. One woman and 12 men experienced major bleeding. Four had intracranial bleeding: 2 cases were fatal and 2 were nonfatal. During treatment with mini-dose warfarin, warfarin plus aspirin, aspirin, and adjusted-dose warfarin, the annual rate of major bleeding was 0.8%, 0.3%, 1.4%, and 1.1%, respectively (P = .20). After 3 years of treatment the cumulative rate of any bleeding was 24.7%, 24.4%, 30.0%, and 41.1% (P = .003), respectively. Increasing INRvalue (P<.001) and prior myocardial infarction (P = .001) were independent risk factors for bleeding, whereas increasing age was not. CONCLUSIONS: Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding. The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy (INR, 2.0-3.0).
warfarin versus aspirin
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1: Lancet. 1989 Jan 28;1(8631):175-9. Related Articles, Links
Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study.
Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B.
Department of Neurology, University Hospital, Copenhagen, Denmark.
From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.
Monday, January 29, 2007
BAFTA (Birminham atrium fibrillation treatment of the aged.
Dear Dr Mant
My medical doctor diagnosed a atrium flatter 23 November 2006, and
prescribed me Marcoumar. By blood controle the INR has to be between 2
and 3.
I am a simple veterinary surgeon, 82 years old and have to use now and
than a couple of celebrex pills, when gout comes up. Moreover I use
omeprazole to keep my stomach quiet. To keep my blood pressure adequate
I use 5mg amlodipine and 4mg perindopril and since my atrium flatter 50
mg atenolol. I have no troubles with my atrium fibrillation and if my
doctor would not have told me, I would not have noticed it.
Reading an article in Neurology 2007; 68: 116-121 by M.L. Flaherty et al.:
The increasing incidence of anticoagulant-associated intracerebral hemorrhage,
I think maybe it is better to use 80mg aspirin with or without persantin (pirydamole)
to avoid anticoagulant-associated intracerebral hemorrhage.
I would be much obliged to you, if you let me know if you can agree with
my supposition.
sincerely yours Jan Goossens.
aspirin versus warfarin
Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269].
Department of Primary Care & General Practice, University of Birmingham, UK. j.w.mant@bham.ac.uk
BACKGROUND: Atrial fibrillation (AF) is an important independent risk factor for stroke. Randomised controlled trials have shown that this risk can be reduced substantially by treatment with warfarin or more modestly by treatment with aspirin. Existing trial data for the effectiveness of warfarin are drawn largely from studies in selected secondary care populations that under-represent the elderly.The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study will provide evidence of the risks and benefits of warfarin versus aspirin for the prevention of stroke for older people with AF in a primary care setting. STUDY DESIGN: A randomised controlled trial where older patients with AF are randomised to receive adjusted dose warfarin or aspirin. Patients will be followed up at three months post-randomisation, then at six monthly intervals there after for an average of three years by their general practitioner. Patients will also receive an annual health questionnaire.1240 patients will be recruited from over 200 practices in England. Patients must be aged 75 years or over and have AF. Patients will be excluded if they have a history of any of the following conditions: rheumatic heart disease; major non-traumatic haemorrhage; intra-cranial haemorrhage; oesophageal varices; active endoscopically proven peptic ulcer disease; allergic hypersensitivity to warfarin or aspirin; or terminal illness. Patients will also be excluded if the GP considers that there are clinical reasons to treat a patient with warfarin in preference to aspirin (or vice versa).The primary end-point is fatal or non-fatal disabling stroke (ischaemic or haemorrhagic) or significant arterial embolism. Secondary outcomes include major extra-cranial haemorrhage, death (all cause, vascular), hospital admissions (all cause, vascular), cognition, quality of life, disability and compliance with study medication.
PMID: 12939169 [PubMed - indexed for MEDLINE]
religion
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| .News about the future of Consciousness | ||
 |  Religion is intimately interwoven with human biologyThere is reason to believe that, to some degree, spirituality is hard-wired into the human nervous system. Recent experiments using thermal imaging indicate that brain activity during a "transcendent" experience is highest in the limbic system, that part of the brain which is associated with emotions and motivation, and in the connecting hypothalamus, amygdala and the hippocampus. Neurobiologists Andrew Newberg and Eugene d'Aquili have conducted research in the field of "neurotheology" using brain imaging technology ( Single Photon Emission Computed Tomography, or SPECT for short ). They suggest that "religion is intimately interwoven with human biology." Their studies of praying Franciscan nuns and meditating Buddhist monks reveal that certain religious experiences, like meditation and prayer, are linked to increased activity and changes in the structure of the brain and nervous system. | |
 | The Mystery of Consciousness by Steven Pinker in Time Magazine [...] As every student in Philosophy 101 learns, nothing can force me to believe that anyone except me is conscious. This power to deny that other people have feelings is not just an academic exercise but an all-too-common vice, as we see in the long history of human cruelty. Yet once we realize that our own consciousness is a product of our brains and that other people have brains like ours, a denial of other people's sentience becomes ludicrous. "Hath not a Jew eyes?" asked Shylock. Today the question is more pointed: Hath not a Jew--or an Arab, or an African, or a baby, or a dog--a cerebral cortex and a thalamus? The undeniable fact that we are all made of the same neural flesh makes it impossible to deny our common capacity to suffer. [...] | |
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dr. Flaherty
Dear Dr. Goossens,
I am afraid it is not possible for me to provide you personal medical
advice in this context.
The data in our paper measure trends in the overall population, and are
less helpful when advising individual patients. A study in England
called BAFTA is comparing aspirin to warfarin in older patients with
atrial fibrillation, however the results are not yet known. When they
are available they may be very helpful in your case.
Until that time, I suggest you discuss your concerns and review the
potential risks and benefits of warfarin with a doctor you trust.
Warfarin is very effective for preventing ischemic stroke in patients
with atrial fibrillation and so for many patients it is still a good
choice. E-mail: matthew.flaherty@uc.edu
Best regards,
Matthew Flaherty
-----Original Message-----
From: Jan Goossens [mailto:roodbont@zonnet.nl]
Sent: Wednesday, January 24, 2007 1:07 PM
To: Flaherty, Matthew (flaherm)
Subject: AAICH
Dear Doctor Flaherty
My medical doctor diagnosed a atrium flatter 23 November 2006, and
prescribed me Marcoumar. By blood controle the INR has to be between 2
and 3.
I am a simple veterinary surgeon, 82 years old and have to use now and
than a couple of celebrex pills, when gout comes up. Moreover I use
omeprazole to keep my stomach quiet. To keep my blood pressure adequate
I use 5mg amlodipine and 4mg perindopril and since my atrium flatter 50
mg atenolol. I have no troubles with my atrium fibrillation and if my
doctor would not have told me, I would not have noticed it.
Reading your article in Neurology I think maybe it is better to use 80
mg aspirin with or without persantin (pirydamole) to avoid AAICH.
I would be much obliged to you, if you let me know if you can agree with
my supposition.
sincerely yours Jan Goossens.
hypertension
Hypertension better controlled in USA than Europe
24 January 2007
Study findings published in the Archives of Internal Medicine suggest that hypertension is treated more effectively in the USA than in Europe.
The study showed that US patients were started on treatment at lower blood pressure (BP) levels, and were more likely to receive intensive treatment and have their BP under control than their European counterparts.
Speaking to MedWire News, study co-author Caleb Alexander (University of Chicago, Illinois, USA) said the findings do probably reflect differences between US and European guidelines, but also emphasized the potential role of “differences in healthcare financing, coverage, and delivery across the countries examined.”
To investigate why BP levels tend to be lower in US than in European populations, the researchers studied data from a clinic-based survey of 21,053 patients who visited 1284 primary care physicians and 291 cardiologists in the USA, Spain, Germany, France, Italy, and the UK.
The results indicated that US physicians initiate treatment at lower BP levels than their European peers, with patients’ average pre-treatment levels at 161/94 mmHg in the USA compared with 167-173/96-99 mmHg in European countries.
Systolic and diastolic BP levels were 5.3-10.2 mmHg and 1.9-5.3 mmHg lower, respectively, in US patients than in patients from European countries.
In addition, adequate BP control was seen more frequently in US than in European patients, with 63% of US patients at 140/90 mmHg or below compared with 31% in Italy, 36% in the UK, 40% in Spain and Germany, and 46% in France.
Furthermore, US patients with poorly controlled hypertension were more likely to have a change or increase in their medication than European patients, at 32% versus 14-26%.
With the exception of thiazides, which were prescribed consistently across groups, there were considerable cross-national variations in the classes of drug used, but these variations and resultant cost differences did not seem to affect BP control.
Interestingly, use of more than one antihypertensive agent – known to be more effective than simply escalating the dose of the first agent to improve control – was also most frequent in the USA, at 64% compared with 44-59% across European countries.
Alexander emphasized that the disparity found in the study is not the most important issue, and that there is an epidemic of untreated hypertension in all of these countries. Furthermore, he noted that diet and exercise remain the first important steps before pharmacologic therapy is initiated.
“Our study should be a call to action for all physicians to more aggressively identify and treat patients with high blood pressure who have failed non-pharmacologic therapy,” he said.
Arch Intern Med 2007: 167: 141-147
stem cells
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| January 14, 2007 | | |
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| A Stroke for Stem Cells | | |
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| The brain becomes a target in stem cell clinical trials | | |
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| The first stem cell therapy targeting a major brain disorder, chronic stroke, could begin clinical trials this year if the U.S. Food and Drug Administration approves the request filed in December by stem cell firm ReNeuron in Guildford, England. This latest treatment suggests stem cell therapies are growing not only in number but in ambition. Chronic stroke, in which patients suffer from permanent infirmity, is the leading cause of adult disability in the developed world. It afflicts 25 million people worldwide, and the number of new cases is rising 7 percent annually, mostly because of an aging population. "Right now there's next to nothing for treating chronic stroke, and what there is addresses the symptoms rather than the cause," says neurologist Justin Zivin of the University of California, San Diego. Stem cells have the potential to regenerate body parts. In prior stroke studies on animals, stem cells injected into the brain or bloodstream migrated to sites of damage, apparently drawn by signals from damaged cells. This migration may happen because the repair pathways initiated by the damaged cells are similar to pathways triggered during embryonic development, where stem cells are key, explains ReNeuron co-founder and chief scientific officer John Sinden. A major concern about stem cells centers on how unstable they can become when grown in the lab. ReNeuron can generate large numbers of stable cell lines by engineering cells with a modified version of the gene c-myc. This gene promotes cell division while activating genes that prevent chromosomal abnormalities. The scientists can switch c-myc on or off by introducing or withholding a synthetic compound. ReNeuron developed cells for brain damage by splicing their modified c-myc into human fetal brain tissue obtained from a U.S. cell bank. They tested 120 neural stem cell lines in the lab for stability and robustness and in animals for the capacity to engraft with minimal immune rejection. Two lines showed potential: ReN001, which ReNeuron is aiming at stroke, and ReN005, which is under research for Huntington's disease. In studies with rats that experienced stroke, ReN001 significantly improved sensory and motor function. The stem cells probably did not replace the massive number of cells lost during stroke, Sinden clarifies. Rather the cells most likely pumped out chemicals that activated repair pathways, resulting in new blood vessels and brain cells. If their phase I clinical trial to test the safety and preliminary efficacy of this therapy gains approval, University of Pittsburgh researchers will test the therapy on 10 patients who suffer from chronic ischemic stroke--the most common form, in which clots block blood flow. Ten million to 20 million cells will be implanted directly in the brain through a small hole in the skull, and patients will be monitored over 24 months. ReNeuron has partnered with BioReliance in Glasgow, Scotland, to scale up cell production; the company has roughly one million ReN001 doses currently on hand, Sinden estimates. Past clinical trials of stem cell therapies for chronic stroke patients used cells derived from tumors in humans and brain tissue from fetal pigs. ReNeuron's fetal cells "are closer to the neurons in [healthy] people than others used before, so they might be more effective," Zivin says. "What ReNeuron has done to create this cell line is ambitious and well thought out," adds neurologist Sean Savitz of Harvard Medical School. Savitz notes, however, that c-myc is associated not only with stem cells and development but also with cancer. "This is definitely not to say that it will promote tumors," he says, but the researchers "will have to continue to convince the scientific community that the cells will not divide unchecked the way they do in tumors." UPDATE: The FDA has put ReNeuron's request for approval of ReN001 on hold, citing the need for additional information. ReNeuron says that the concerns are readily addressable and that preclinical studies now underway should answer the FDA's questions. ADVERTISEMENT         | |  |
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| © 1996-2007 Scientific American, Inc. All rights reserved. Reproduction in whole or in part without permission is prohibited. | | |
Wednesday, January 24, 2007
meer over dit onderwerp
Information from IndustryDaytrana™ (methylphenidate transdermal system)The first and only transdermal ADHD medication. |
January 9, 2007 — A new study suggests that the rate of intracerebral hemorrhage (ICH) associated with the use of anticoagulants increased five-fold during the 1990s and up to 10-fold in the elderly.
Most of the increase, the researchers say, is explained by the growing use of warfarin in patients with atrial fibrillation (AF), after a number of studies during that decade confirmed that treatment reduced stroke in this population. These findings of an accompanying increase in ICH, a known risk with warfarin therapy, do not mean that the benefits may not still outweigh the risks for many people, they say.
"Our findings should not discourage the use of warfarin when it's appropriate," lead author Matthew L. Flaherty, MD, from the University of Cincinnati Medical Center, in Ohio, said in a press release from the American Academy of Neurology. "Doctors can use these findings to make sure they are weighing the risks and benefits of warfarin use for their patients. For researchers, these results may stimulate efforts to develop safer alternatives to warfarin and better treatments for people with brain hemorrhages."
The report is published in the January 9 issue of Neurology.
Growing Warfarin Use
Warfarin use has increased since publication during the 1990s of such landmark studies as the Stroke Prevention in Atrial Fibrillation (SPAF) trials, among others, showing that anticoagulation with warfarin could significantly reduce the risk for stroke in patients with AF. The risk/benefit ratio for warfarin treatment is good when patients are at high risk for stroke but "narrower" when used in primary prevention in the elderly, where the benefit may be offset by bleeding risk, they write.
Although ICH is the "most-feared" complication of treatment, precise estimates of anticoagulant-associated ICH are not available, they note. In this study, Dr. Flaherty and colleagues identified all patients in the Greater Cincinnati/Northern Kentucky area who were hospitalized with first-ever ICH during 3 periods: 1988, 1993–94, and 1999 — that is, before and after the major anticoagulant trials in AF. The hemorrhages were considered anticoagulant-associated if the patient was on warfarin or heparin.
They found the annualized rate of anticoagulant-associated ICH (AAICH) increased significantly over the 3 periods, as did the percentage of overall ICH cases that it represented.
Anticoagulation Associated Intracerebral Hemorrhage Rates 1998–1999
| End Point | 1988 | 1993/94 | 1999 | P for trend |
| Annual incidence rate of AAICH per 100,000 (95% CI) | 0.8 (0.3–1.3) | 1.9 (1.1–2.7) | 4.4 (3.2–5.5) | < .001 |
| % of all ICH cases | 5 | 9 | 17 | < .001 |
"To place the burden of AAICH in context, its overall incidence is now only slightly less than subarachnoid hemorrhage, which occurs at a rate of 6.6 cases per 100,000 persons in our metropolitan area," Dr. Flaherty et al note.
For those patients 80 years of age and older, the rate increased even more significantly, from 2.5 cases per 100,000 persons in 1988 to 45.9 cases in 1999 (P < .001 for trend). They also looked at the incidence rates of patients hospitalized with first-ever ischemic cardioembolic stroke in the latter 2 of these periods, to assess the benefit of warfarin, the use of which quadrupled on a per-capita basis between 1988 and 1999, they note. They report that the incidence of cardioembolic stroke either overall or due to AF did not change significantly between 1993–94 and 1999. Annualized Incidence Rates (per 100,000 Persons) of Cardioembolic Ischemic Stroke in the Greater Cincinnati/Northern Kentucky Population
| End Point | 1993–94 (95% CI) | 1999 (95% CI) | P for trend |
| Cardioembolic ischemic stroke | 31.1 (27.9–34.3) | 30.4 (27.3–33.5) | .65 |
| Cardioembolic ischemic stroke due to AF | 22.0 (19.3–24.7) | 20.6 (18.1–23.2) | .44 |
However, these results are at odds with other studies that have shown declines in ischemic stroke in AF, they point out. In addition, they note, the prevalence of AF in the United States appears to be increasing over time, regardless of age. "Given this fact, rates of cardioembolic stroke might have been expected to increase and therefore we believe that our static incidence rates likely represent benefit from warfarin use in prevention of ischemic stroke."
The study was supported in part by the National Institute for Neurological Disorders and Stroke.
Neurology. 2007;68:116-121.
atrial fibrillation and season
Seasonal variation in paroxysmal AF found
19 January 2007
Paroxysymal atrial fibrillation (AF) varies significantly with the seasons of the year, research shows.
Japanese investigators report that maximum and minimum incidences of paroxysmal AF occur in autumn and summer, respectively.
"Although circadian variations are known to affect paroxysmal AF, seasonal patterns have not been well characterized," Eiichi Watanabe (Fujita Health University School of Medicine, Toyoake) and team note.
To investigate, the researchers evaluated paroxysmal AF patterns in 237 patients, recorded over a 5-year period using 24-hour Holter electrocardiogram (ECG) monitoring.
Overall, they identified 258 paroxysmal AF episodes in 12,390 consecutive recordings.
The incidence of paroxysmal AF was highest in September and lowest in June, the researchers report in the journal Heart Rhythm.
The respective relative risks (RRs) of paroxysmal AF, determined with respect to the overall mean incidence, at these times were 1.40 and 0.52.
The incidence of paroxysmal AF also showed an autumn peak and a summer minimum among all patients, with RRs of 1.21 and 0.66, respectively.
The seasonal and monthly variations in paroxysmal AF were not influenced by age, or clinical variables such as underlying disease and medications.
In addition, the researchers found there was a significant inverse relationship between the incidence of paroxysmal AF and the length of daylight in patients aged under 65 years. In contrast, there was no correlation between paroxysmal AF and the mean outdoor temperature in any patients.
"The seasonal variation in paroxysmal AF demonstrated by our study, showing a peak incidence in the autumn months, could have important clinical implications," the authors conclude.
They add that understanding the role of the seasonal stresses and other mechanisms may lead to novel treatments of this arrhythmia.
Heart Rhythm 2007; 4: 27-31
warfarin en hersenbloeding
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© 2007 American Academy of Neurology
The increasing incidence of anticoagulant-associated intracerebral hemorrhage
From the Departments of Neurology (M.L.F., B.K., D.W., D.K., K.A., C.J.M., M.H., J.P.B.) and Environmental Health (P.S.), University of Cincinnati College of Medicine, OH.
Address correspondence and reprint requests to Dr. Matthew L. Flaherty, 231 Albert Sabin Way, MSB Room 5060, University of Cincinnati Medical Center, Cincinnati, OH 45267-0525; e-mail: matthew.flaherty@uc.edu
Objective: To define temporal trends in the incidence of anticoagulant-associated intracerebral hemorrhage (AAICH) during the 1990s and relate them to rates of cardioembolic ischemic stroke.
Methods: We identified all patients hospitalized with first-ever intracerebral hemorrhage (ICH) in greater Cincinnati during 1988, from July 1993 through June 1994, and during 1999. AAICH was defined as ICH in patients receiving warfarin or heparin. Patients from the same region hospitalized with first-ever ischemic stroke of cardioembolic mechanism were identified during 1993/1994 and 1999. Incidence rates were calculated and adjusted to the 2000 US population. Estimates of warfarin distribution in the United States were obtained for the years 1988 through 2004.
Results: AAICH occurred in 9 of 184 ICH cases (5%) in 1988, 23 of 267 cases (9%) in 1993/1994, and 54 of 311 cases (17%) in 1999 (p <> persons was 0.8 (95% CI 0.3 to 1.3) in 1988, 1.9 (1.1 to 2.7) in 1993/1994, and 4.4 (3.2 to 5.5) in 1999 (p <> trend). Among persons aged 
80, the AAICH rate increased from 2.5 (0 to 7.4) in 1988 to 45.9 (25.6 to 66.2) in 1999 (p < 0.001 for trend). Incidence rates of cardioembolic ischemic stroke were similar in 1993/1994 and 1999 (31.1 vs 30.4, p = 0.65). Warfarin distribution in the United States quadrupled on a per-capita basis between 1988 and 1999.
Conclusions: The incidence of anticoagulant-associated intracerebral hemorrhage quintupled in our population during the 1990s. The majority of this change can be explained by increasing warfarin use. Anticoagulant-associated intracerebral hemorrhage now occurs at a frequency comparable to subarachnoid hemorrhage.
Supported in part by National Institute of Neurological Disorders and Stroke (R-01-NS 030678).
Disclosure: The authors report no conflicts of interest.
Received June 12, 2006. Accepted in final form September 28, 2006.
Related articles in Neurology:
- January 9 Highlights
Neurology 2007 68: 86-87.[Full Text]
This article has been cited by other articles: (Search Google Scholar for Other Citing Articles)
| |  | |   Intracerebral Hemorrhage Associated with Warfarin Journal Watch (General), January 23, 2007; 2007(123): 2 - 2. [Full Text] | |
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