The Role of Aspirin and Heparin in Ischemic Stroke-Part IV

(3/29/06)- The anticlotting drug Plavix had over $6.2 billion in sales last year for its distributors Sanofi-Aventis SA of France and Bristol-Myers Squibb of New York. The drug has been approved for usage, along with aspirin, after a patient has had a heart attack, but the question has arisen if the drug would be useful in preventing heart attacks in individuals who are at high risk for having one. Plavix was the second most widely sold drug in the world last year, trailing only Pfizer's Lipitor in 2005.

The answer to this question seems to be no, based on the results of a study of 15,000 patients who were deemed to be at high risk for having a heart attack. These individuals were at high risk because they had had a stroke, or a blocked artery in the leg.

The drug, which is also known generically as clopidogrel, was found to be of no help in preventing a heart attack. The Plavix offered no benefit over standard low-dose aspirin therapy, and in fact it significantly increased the risk of internal bleeding. In fact, when combined with aspirin it was determined that there was only a 1-% reduction in the risk of heart attack.

The study, called Charisma, was presented at the annual scientific meeting of the American College of Cardiology in Atlanta. Both aspirin and Plavix inhibit platelets from forming clots. Researchers found that 6.8% of patients with the combination of Plavix and aspirin had either a heart attack or a stroke or died of cardiovascular disease-compared with 7.4% who were on aspirin plus placebo.

Among patients without established cardiovascular disease, the rate of death from cardiovascular causes was 3.9% for those taking Plavix and aspiriin, compared with 2.2% for those taking aspirin alone.

Plavix is approved for patients with a recent heart attack or unstable chest pain, and for people treated with drug eluting stents. Studies have shown that when such patients stop Plavix, even while continuing aspirin, they significantly increase the risk of developing a clot in the stent.

(9/30/04)- In a review article of aspirin and heparin in acute ischemic stroke in older patients, Gribitz and Sandercock conclude, "Aspirin is …the antithrombotic drug of choice in the treatment of acute ischaemic [sic] stroke". Stroke is the leading cause of disability in this country.

Many vascular specialists say that two diagnostic tests are available but underused in helping to prevent strokes from occurring. These two tests are the carotid ultrasound test and the ankle-brachial test. Vascular doctors will begin a campaign to have Medicare cover the cost of these two tests beginning at the age of 65.

The cost of each of these tests can vary from about $45 to several hundreds of dollars depending on where the test is taken. There is a private company called Life Line Screening that offers these two tests, plus ultrasound tests for aortic aneurysms and an exam for osteoporosis for $129. Hospitals that do the carotid artery test charge about $250 for this test.

The American Vascular Association offers free screenings from time to time. There will be one at the Grand Hyatt Hotel in New York City on October 1. For a list of other sites where these screenings will take place go to The Society of Interventional Radiology will also offer free screening at various sites during the year. To obtain a list of where these screenings will be held go to

Those who are at high risk of incurring strokes include those who have a family history of stroke, those who have diabetes or those who have high blood-lipid levels. There is evidence that, once carotid artery blockage is found, either drugs or surgery can treat it. A blockage of the carotid artery that exceeds 80% is considered sufficient a level to warrant surgery. The carotid artery is near the neck's surface, so an ultrasound test done by a professional sonographer can detect the problem.

There is a turf war going on among medical professionals in this area. There are 2,400 vascular surgeons and physicians in this country and there are 22,000 cardiologists in the U.S. The American Stroke Association, which is made up of neurologists, says it is considering promoting these tests, but it isn't sure how cost effective the tests are.

The ankle-brachial test involves taking the blood pressure of the patient at the ankle and the brachial artery in the upper arm. The comparative ratios of the two should be about 1 to 1, and is known as the ABI ratio. A score of 0.9 means blood-flow blockage is significant enough to be considered abnormal

Stroke is the second most common cause of death worldwide, and the third most common cause of death in the U.S. after heart disease and cancer. Stroke is most predominantly a disease of the elderly. Over two-thirds occur in people over 65 years of age, and half of all strokes occur in people greater than 70 years of age. About 80% of acute strokes are caused by thrombotic or embolic occlusion of a cerebral artery, leading to cerebral infarction. The remaining 20% of strokes are due either to intracerebral or subarachnoid hemorrhage. If CT scanning shows an intracranial hemorrhage, then thrombolytic and antithrombic therapy should be avoided.

About 10% of all patients with acute ischemic stroke will die within 30 days of stroke onset, usually as result of the effects of brain swelling in large-volume infarcts. Of patients who survive the acute stroke, about half will experience some level of disability after 6 months, and will require varying amounts of assistance in order to carry out their activities of daily living.

Pharmacological treatment of acute ischemic stroke aims to limit the degree of brain damage and thereby reduce any long-term physical impairment and disability. Fontanarosa and Winkler suggest that there is insufficient evidence to support the routine use of thrombolytic therapy in the majority of older patients with ischemic stroke.

Irrespective of patient’s age, evidence suggests routinely starting aspirin within 48 hours of acute ischemic stroke, unless clear evidence exists to the contrary. Aspirin prevents recurrent stroke and improves the chance of complete recovery. On the other hand, systemic anticoagulants, such as heparin, do not appear to offer any clear benefits overall, and should not be used routinely. Please see our article Beta-Blockers and ACE Inhibitors in the Battle against Heart Disease and Failure

The cardioprotective effects of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) have been well established through clinical research. The newer selective cyclooxygenase 2 (COX-2) inhibitors effects on the cardiovascular system are not so clear. In fact, there are suggestions in the research literature that COX-2 inhibitors "might tip the clotting cascade towards a prothrombotic state". Mukherje et al did a meta-analysis of several clinical trials of COX-2 and conclude, "[C]hronic (emphasis added) use of COX-2 inhibitors might be associated with an increased incidence of thrombic events". The reason for this appears to be that COX-2 is responsible for the synthesis of prostaglandin, a vasodilator and anti-platelet aggregation factor. This study opens the question of what is the safe length to use COX-2 inhibitors. Only further research will answer this question. In the meantime, physicians would be well advised to proceed with caution in the chronic use of this therapeutic medication. Treatment guidelines would aid in this endeavor.

Please also see our article: Aspirin as a Preventative Therapy against Cardiovascular Events


Fontanrosa P. & Winkler M. Timely and appropriate treatment for acute stroke: What s missing from this picture. JAMA 1998; 279:1307-1308.

Gribitz G. & Sandercock PAG. Aspirin and Heparin in Acute Ischemic Stroke in Older Patients. Drug & Aging 2000; Jul 16 (1): 29-36.

Mukherjee D, et al. Cardiovascular risks of Cox-2 inhibitors. Am J Med Assoc. 2001; 286:954-959.

Stroke I-General Information
Stroke II-Stroke Treatment
Stroke Part III : Reducing Risk


by Harold Rubin, MS, ABD, CRC, Guest Lecturer
March 29, 2006

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