Aspirin as effective as Warfarin - New Study confirms

[H.E.pumper]

Aspirin as Effective as Warfarin for Heart Failure: Study

Doctors, patients may opt for cheaper, over-the-counter aspirin, researchers say

By Mary Elizabeth Dallas

WEDNESDAY, May 2 (HealthDay News) -- Aspirin is just as effective as the blood-thinner warfarin in preventing stroke and death in heart failure patients with a normal heart rhythm, a landmark study indicates.

Although the two treatments are equally effective, researchers from Columbia University in New York City said their findings could prompt more doctors and patients to choose aspirin because it is much cheaper.

The 10-year study was the largest comparison of aspirin and warfarin (Coumadin) in the treatment of heart failure patients. In conducting the comparison, researchers followed more than 2,300 patients in 11 countries on three continents. Study participants were assigned randomly either to aspirin or warfarin, and neither the patient nor their doctor knew which medication each patient was taking.

The investigators found that the combined risk of death, stroke and cerebral hemorrhage during the study period was 7.47 percent for patients taking warfarin and 7.93 percent for patients taking aspirin -- a difference that is statistically insignificant.

Although patients taking warfarin had a nearly 50 percent lower risk for stroke than those taking aspirin, their risk for major bleeding was twice as high. As a result, the researchers argued that the benefits do not outweigh the risks. They noted, however, that taking warfarin for four years or more may be more effective at preventing stroke and death.

"With at least 6 million Americans -- and many more around the world -- suffering from heart failure, the results of the ... study will have a large public health impact," Dr. Walter Koroshetz, deputy director of the U.S. National Institute of Neurological Disorders and Stroke, said in a Columbia University news release. "Patients and their physicians now have critical information to help select the optimum treatment approach. The key decision will be whether to accept the increased risk of stroke with aspirin or the increased risk of primarily gastrointestinal hemorrhage [stomach bleeding] with warfarin."

Although the study, published in the May 3 issue of the New England Journal of Medicine, found aspirin and warfarin to be equally effective, the researchers noted that aspirin may be a more likely choice for doctors and patients.

Like warfarin, aspirin reduces the risk of stroke due to a clot or blockage. Aspirin, however, is cheaper and available over the counter. Warfarin also requires a strict dosing regimen, including regular blood tests to monitor patients' clotting levels.

"Since the overall risks and benefits are similar for aspirin and warfarin, the patient and his or her doctor are free to choose the treatment that best meets their particular medical needs," principal investigator, Dr. Shunichi Homma, associate chief of the cardiology division at New York-Presbyterian/Columbia and a professor of medicine at Columbia's College of Physicians and Surgeons in New York City, said in the news release. "However, given the convenience and low cost of aspirin, many may go this route."

SOURCE: Columbia University, news release, May 2, 2012



http://www.nlm.nih.gov/medlineplus/news/fullstory_124760.html

Tom

 

[AgilityDog]

That's heart failure. NOT mechanical valves.
That's normal rythym, not a-fib.
This seems to me to be a study of nothing significant. I don't know that heart failure patients, with that as their only ailment, have a higher rate of stroke than anyone else.

 

[chaconne]

Although patients taking warfarin had a nearly 50 percent lower risk for stroke than those taking aspirin, their risk for major bleeding was twice as high. As a result, the researchers argued that the benefits do not outweigh the risks. They noted, however, that taking warfarin for four years or more may be more effective at preventing stroke and death.

To me, this is the significant find. Warfarin is more effective at reducing the risk of stroke, but also twice as high a risk for major bleeding. Personally, I'm more afraid of having a stroke. I wonder what INR range is used and what the aspirin dose is?

 

[Protimenow]

I'm with Laurie on this -- it doesn't apply to people with mechanical valves or A-Fib. 'Heart Failure' may be a bit general, too, but I'm assuming it to mean the inability of the heart to expel enough blood. I'm not sure if having platelets that are a bit more slippery than without taking aspirin versus having blood that takes a bit longer to clot are serious issues for 'heart failure.' In fact, this is the first time I've heard of warfarin being used to treat heart failure.

With the design of the study, it suggests that there was no INR monitoring being performed, so the risk of bleeds may have been higher than the aspirin group. It's irresponsible to give warfarin (except, perhaps, in really small doses that may have little or no effect), without monitoring the patient's INR. For a study of this type, it's hard to NOT know what the patients in a randomized study group are taking - IF all patients have INRs taken regularly. (Those taking aspirin will have INRs close to 1.0 - those taking warfarin should have INRs somewhat higher - UNLESS a subtherapeutic dose of warfarin is being given).

Also - the comment about warfarin being much more expensive than aspirin is pretty bogus. True, I can get a bottle of 200 325 mg aspirin at my 99 Cent store, but generic warfarin is only about a dime a pill ($10 for 90). The days of the $1 per pill coumadin are gone (except for those patients with great insurance or who believe the smoke that the manufacturers used to create that painted warfarin as inferior).

For all of us valvers, and those with A-Fib, this study is totally irrelevant.

 

[dick0236]

I believe I'll wait a few years, maybe twenty or so, before making that kind of JUMP......strokes are forever.

 

[H.E.pumper]

That's heart failure. NOT mechanical valves.
That's normal rythym, not a-fib.
This seems to me to be a study of nothing significant. I don't know that heart failure patients, with that as their only ailment, have a higher rate of stroke than anyone else.

Are those who die of complications due to their mechanical valve listed as dying of 'heart failure'? I think the term 'heart failure' may cover all the bases; the study report is not very specific. I'm still deciding tissue vs mechanical so this study interested me.


Tom

 

[H.E.pumper]

To me, this is the significant find. Warfarin is more effective at reducing the risk of stroke, but also twice as high a risk for major bleeding. Personally, I'm more afraid of having a stroke. I wonder what INR range is used and what the aspirin dose is?

Does taking aspirin affect one's INR? I've been taking aspirin daily for about 20 years or so; initially the low dose 81mg but changed to normal dose, 325mg, about five years ago. I had a blood test last week as part of my pre-op for my June 6th AVR job and my INR was 1.0. (yes, I took one 325mg aspirin the morning before the test). I understood that everyone not on blood thinners has an INR of 1.0. Am I right on this?


Tom

 

[RBCola]

Does taking aspirin affect one's INR? I've been taking aspirin daily for about 20 years or so; initially the low dose 81mg but changed to normal dose, 325mg, about five years ago. I had a blood test last week as part of my pre-op for my June 6th AVR job and my INR was 1.0. (yes, I took one 325mg aspirin the morning before the test). I understood that everyone not on blood thinners has an INR of 1.0. Am I right on this?


Tom

Aspirin has absolutely no effect on your INR. It works by inhibiting platelets from clumping together to form clots. Warfarin is working by inhibiting clotting factors used to hold the platelets together during clotting. Think of platelets as the bricks and the clotting factors as mortar.

So yes, if you are only taking aspirin, your INR will be around 1. INR is a test to measure how well/fast your clotting factors are working.

Sent from my SGH-T989 using Tapatalk 2

 

[AgilityDog]

No, mechanical valvers do not all have heart failure, though some of us do,
and not all people with heart failure have mechanical valves, though a few do.

I happen to have both. "Heart failure" is generally the reduced ability of the heart to pump blood, usually because of muscle damage or other structural damage from one or more causes, including MI, cardiomyopathy AND/OR valve problems. Usually if you have heart failure, you have a reduced ejection fraction.

Basically, this study does not relate to mechanical valvers.
When I spoke to my coumadin manager last week (who is someone I actually think knows what she's talking about), she said there were NO realistic plans to substitute any of the newer anticoagulants for warfarin for us valvers in the foreseeable future. And certainly not with aspirin.

I'm fine with that. I chose this over additional surgeries.

 

[Protimenow]

The point that I was trying to make about the study was that it wasn't truly 'blind.' The people giving out the medications should have known WHICH medication their subjects were getting -- because, presumably, the ones that took warfarin had to be monitored to make sure that their INRs didn't get TOO high (but were at some therapeutic level), and no such testing was needed for those taking aspirin.

They didn't define 'heart failure' in the materials that the link referred to, so it's unclear what degree of failure was being 'treated.'

The report, as quoted above, doesn't seem particularly rigorous in its design, implementation, or underlying hypothesis.

 

[ElectLive]

Tom - There was a thread a while back about Aspirin and Warfarin you might find helpful: http://www.valvereplacement.org/forums/showthread.php?39961-Random-(stupid-)-question-aspirin

Why are you now taking Aspirin 325? My reason for asking is that if you happen to already have another risk factor for stroke prior to valve replacement, this may impact what's required after the new valve. Depending on your answer, this may not apply to you, but just to finish the thought, some patients with additional risk factors need to take Warfarin even with a tissue valve and also the only legitimate Warfarin alternative studies being investigated for mechanical valve patients are only for the lowest risk group of patients.

 

[dick0236]

I understood that everyone not on blood thinners has an INR of 1.0. Am I right on this?
Tom

Yes, a normal person not on blood thinners will have an INR of 1.0 +/-. Many who home test, stick their wife, husband, or some other unsuspecting soul, not on warfarin, every now and then to check the accuracy of their INR meter.

 

[Lynlw]

As others said, this is only for a select group of patients with heart failure, doesn't have anything to do with valvers or people with AFIB, they are excluded

FWIW Im pretty sure it is this trial http://clinicaltrials.gov/ct2/show/NCT00041938?term=WARCEF&rank=1 Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

Primary Outcome Measures:
•Comparison of aspirin and warfarin to determine if either is superior for preventing the combined endpoint of all-cause mortality and stroke in patients with left ventricular ejection fraction <35%.

here are the Criteria MY Bold

Criteria
Inclusion Criteria

•Cardiac EF <=35% by radionuclide ventriculography, left ventriculography or quantitive echocardiographic measurement or an echocardiographic Wall Motion Index of <=1.2, within three months of enrollment. The patient's clinical cardiac state at enrollment should be similar to their state at the time of the qualifying echocardiogram. The qualifying left ventricular function measurement must be obtained at least three months after an MI, coronary bypass grafting, PTCA, and at least one month after pacemaker insertion. Patients scheduled for mitral valve repair should have qualifying echo after surgery.
•Modified Rankin score <=4.
•Patient must be taking ACE inhibitors. If intolerant of ACE inhibitor, patient must be on angiotensin II receptor blockers or hydralazine and nitrates.
•Patient is able to follow an outpatient protocol (requiring monthly blood tests and clinic visits every four months for the duration of the study) and is available by telephone.
•Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent.
•Patients with recent stroke or TIA within twelve (12) months will be eligible to be included in the recent stroke (RS) subgroup.
•Chronic CHF patients (NYHA I * IV) admitted to the hospital can be randomized prior to discharge if the patient is stable, taking oral medications for 24 hours and ambulatory at the time of discharge. Stable New York Heart Association Class IV patients will be eligible for randomization.

Exclusion Criteria (MY Bold)

•The presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal AF, mechanical valve, endocarditis, intracardiac mobile or pedunculated thrombus, and valvular vegetation.
•Cyanotic congenital heart disease, Eisenmenger's syndrome.•Decompensated heart failure.
•Cardiac surgery, angioplasty, or MI within the past 3 months prior to randomization.
•A contraindication to the use of either warfarin or aspirin, e.g. active peptic ulcer disease, active bleeding diathesis, platelets <100,000*, hematocrit <30, INR >1.3 (if not on warfarin), clotting factor abnormality that increases the risk of bleeding, alcohol or substance abuse, severe gait instability, cerebral hemorrhage, systemic hemorrhage within the past year, severe liver impairment (AST >3x normal*, cirrhosis), any condition requiring regular use of non-steroidal anti-inflammatory agents, allergy to aspirin or warfarin, uncontrolled severe hypertension (systolic pressure >180 mm Hg or diastolic pressure > 110 mm Hg), positive stool guaiac not attributable to hemorrhoids, creatinine >3.0*. *on most recent test done within 30 days prior to randomization
•Patient needs continuing therapy with intravenous heparin or low molecular weight heparin or a specific antiplatelet agent.
•Dementia or psychiatric or physical problem that prevents the patient from following an outpatient program reliably.
•Comorbid conditions that may limit survival to less than five years.
•Pregnancy, or female of childbearing potential who is not sterilized or is not using a medically accepted form of contraception* (see procedure manual). *A pregnancy test is required for all women of childbearing age.
•Enrollment in another study that would conflict with WARCEF.
•Hospitalization for new diagnosis of onset CHF within the past one month or carotid endarterectomy or pacemaker insertion within the past one month prior to randomization .
•Person under 18 years of age.

 

[Lynlw]

With the design of the study, it suggests that there was no INR monitoring being performed, so the risk of bleeds may have been higher than the aspirin group. It's irresponsible to give warfarin (except, perhaps, in really small doses that may have little or no effect), without monitoring the patient's INR. For a study of this type, it's hard to NOT know what the patients in a randomized study group are taking - IF all patients have INRs taken regularly. (Those taking aspirin will have INRs close to 1.0 - those taking warfarin should have INRs somewhat higher - UNLESS a subtherapeutic dose of warfarin is being given).

Also - the comment about warfarin being much more expensive than aspirin is pretty bogus. True, I can get a bottle of 200 325 mg aspirin at my 99 Cent store, but generic warfarin is only about a dime a pill ($10 for 90). The days of the $1 per pill coumadin are gone (except for those patients with great insurance or who believe the smoke that the manufacturers used to create that painted warfarin as inferior

The point that I was trying to make about the study was that it wasn't truly 'blind.' The people giving out the medications should have known WHICH medication their subjects were getting -- because, presumably, the ones that took warfarin had to be monitored to make sure that their INRs didn't get TOO high (but were at some therapeutic level), and no such testing was needed for those taking aspirin.

They didn't define 'heart failure' in the materials that the link referred to, so it's unclear what degree of failure was being 'treated.'

The report, as quoted above, doesn't seem particularly rigorous in its design, implementation, or underlying hypothesis.

Since ths is just a short article or press release, and not a detailed Report or detailed clinic trial results I'm not sure I would assume they werent truly blind or that they had people take Coumadin with out doing INRs or any of the other issues you think made them irresponsible etc.

 

[Protimenow]

Lyn:

The 'monthly blood tests' in the study design may suggest that the study was 'blind' - but I'm concerned that there may have been a subtheraputic dose of warfarin, or else there would have been a risk of hemorrhage in study participants who were most sensitive to warfarin. I don't believe that the study states the dosage (I haven't read the study), but I would be surprised if they used a dose of warfarin that would have caused any problems in the study subjects taking it. (I wouldn't be surprised if the dose was 1-2 mg/day, if that much)

 

[karla]

The point that I was trying to make about the study was that it wasn't truly 'blind.' The people giving out the medications should have known WHICH medication their subjects were getting -- because, presumably, the ones that took warfarin had to be monitored to make sure that their INRs didn't get TOO high (but were at some therapeutic level), and no such testing was needed for those taking aspirin.

They didn't define 'heart failure' in the materials that the link referred to, so it's unclear what degree of failure was being 'treated.'

The report, as quoted above, doesn't seem particularly rigorous in its design, implementation, or underlying hypothesis.

Studies such as this one are generally designed to make sure they truly are as "blind" as possible and the people "giving out the medicines" really do not know what they are giving. The study meds are made to look exactly alike, the packaging is exactly alike, the subjects are treated exactly the same ( ex: everybody gets an INR or whatever at specified times no matter what med they are on), etc. True - if you had someone who had a consistent INR of 3.0 and another with a consistent INR of 1.0, and you were privy to the results, you could certainly guess who was on what but it would still be, technically, a guess. There are built in safeguards in studies so people are not put at risk unnecessarily. While somebody would HAVE to be watching INR results so harm would not come to anyone...it might not be the folks handing out the drugs - and likely aren't.

 

[Protimenow]

I'm well aware of good test design, but I still suspect that if the people giving out the medications get INR results, it wouldn't be much of a stretch to conclude which test subject was getting warfarin and which was getting aspirin. I doubt that the clinicians were operating 'blind', with INR reports for EVERY subject on the study ONLY going to the study administrator. I guess that it's possible that the study administrator (who randomizes the study, monitors results, etc.) COULD have notified the physicians dispensing the drugs if a subject's INR was dangerously high, but this might not have been part of the study design. (This study may have made sense if some sub-therapeutic dose of warfarin was used - perhaps .5 - 1 mg of warfarin - so the INR would have been slightly above 1.0, but not so high that any real intervention by the clinician was necessary).

 

[karla]

the docs don't normally get caught up with details like dispensing the drugs...at least for the studies in which I was the coordinator (administrator). while the docs and i would be aware of all testing results, the pharmacist dispensing the study medication was not.

 

[karla]

also - any study that does not have precautions built in for something like a dangerously abnormal test result should never have gotten past an IRB, whose function is to evaluate not the science of any particular study, but the potential dangers to human subjects.
regardless, it would be extremely unethical to not report - and act on - a dangerously abnormal test result, whether or not it is built into the study design.

 

[Lynlw]

also - any study that does not have precautions built in for something like a dangerously abnormal test result should never have gotten past an IRB, whose function is to evaluate not the science of any particular study, but the potential dangers to human subjects.
regardless, it would be extremely unethical to not report - and act on - a dangerously abnormal test result, whether or not it is built into the study design.

I'm not sure i'd agree with the conclussion, Aspirin as effective as Warfarin- since it seems after 4 years Coumadin "more may be more effective at preventing stroke and death", but thats a different subject,
Sorry I didnt see your posts earlier but I gave up on this thread when I realized people being "concerned" and accusing the doctors at Columbia and the 60some other centers in 11 countries of being irresponsible and not understanding the possible risks wih Coumadin or how to properly run trials, or wether it was "blind" or not all the other complaints about the study and the "study design", based all the concerns on the short article about the press release, and not even the short summery I linked to above, http://clinicaltrials.gov/ct2/show/NCT00041938?term=WARCEF&rank=1 describing it, that clearly stated the dosage of aspirin or the INR
Arms Assigned Interventions
Active Comparator: 1
aspirin 325 mg per day
Active Comparator: 2
warfarin Drug: Warfarin
INR 2.5-3.0; target INR 2.75

let alone looking for other information describing the study in more detail than the short press release that as far as I know MOST articles for the general public are pretty vague describing studies and mainly talk about results/ not indepth discussions but if it helps here is the link to the abstract at pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22551105?dopt=Abstract
If anyone s interested, also the other day i found a pretty good article and video at Columbia's site with a little more detail even describing a little more the way it was blind
MD, NINDS deputy director.

The randomized trial was double-blinded so patient andclinician were both unaware of which drug the patient was taking. The patient was instructed to take pills from two bottles, labeled aspirin and warfarin; one was an active medication, and the other, a placebo. All patients took regular blood tests; results for patients on active aspirin were generated using an algorithm designed by Dr. Thompson. “This process gave greatconfidence that the trial was conducted in an unbiased way,” says Dr. Thompson, who is Professor of Clinical Biostatistics and Clinical Neurology at the Mailman School and College of Physicians and Surgeons, respectively.

http://www.cumc.columbia.edu/news-r...ly-effective-for-most-heart-failure-patients/