New Antiplatelet Agents Effective in Preventing Second Stroke
This report was reviewed for medical and scientific accuracy by Andrew Goodman, MD , Department of Neurology, University of Rochester Medical Center, New York.
Once a person suffers a stroke or even a transient ischemic attack (TIA)-a temporary blockage of an artery in the brain that causes transient symptoms of a stroke-the risk of having a subsequent stroke is greatly increased for that person. This situation requires effective, long-term prevention. Low-dose aspirin is a cost-effective option, but there are newer alternative agents that may be more effective in reducing risk, according to presentations made during the 25th International Stroke Conference, sponsored by the American Stroke Association.
Stroke is the third leading cause of death in the United States. About 30% of stroke victims die within one year-and the proportion is higher among persons over 65 years of age. According to the American Stroke Association, among stroke survivors, about 30% require help in caring for themselves, 20% require assistance walking, and 70% have impairments that keep them from working at their previous jobs.
The risk of suffering a second stroke is 3-10% within the first 30 days of the initial stroke, 5-14% within the first year, and 25-40% within five years. The risk is almost as high after a TIA. Preventive therapy, therefore, is crucial. Antiplatelet agents are recommended for the majority of patients. Some people, however, need another type of blood-thinner, usually warfarin (Coumadin®), and persons with substantial blockages of their carotid artery (which feeds blood to the brain) may also need a surgical procedure, called a carotid endarterectomy.
But the current use of the new antiplatelet agents or even aspirin alone for the prevention of secondary strokes is "appallingly slight for modern medicine," said Bruce M. Coull, MD, Professor and Head of Neurology at the University of Arizona College of Medicine. A recent study of 961 patients at 36 medical centers found that only 38% of patients with a prior stroke or TIA had been receiving antiplatelet therapy at the time of their second stroke, he reported.
Dr. Coull and other specialists at the stroke conference called on physicians to be more aggressive about prescribing antiplatelet therapy to patients at risk for future strokes.
Which Aspirin Dose?
Gregory W. Albers, MD, Director of the Stanford University Stroke Center and chairman of the AHA (American Heart Association) committee that made the recommendations, told physicians that trials comparing low to medium doses and medium to high doses of aspirin found no difference in protection according to dose: low doses of aspirin (81 to 325 mg daily) are just as effective as higher doses (650 to 1,000 mg daily) in preventing secondary stroke, he said.
One recent trial actually found that lower doses of aspirin were more effective than higher doses. The doses are also of similar benefit in reducing the risk of stroke, myocardial infarction, or death from a vascular cause when all these events are analyzed as a group.
Based on their analyses of clinical trials, the AHA committee now advises 50 to 325 mg as a recommended daily aspirin dose for prevention of a second stroke. It is also "reasonable," they added, to go as high as 1,300 mg daily.
"The amount of data from direct comparisons [of aspirin doses] is limited, so it is hard to say what the optimum dose of aspirin is for stroke prevention," Dr. Albers said. "The recommended dose, however, is on the lower side.... What is frustrating," he continued, "is that the relative benefit of aspirin over placebo is quite modest in any of these doses. The risk reduction in combined analyses has been about 13%," he reported. In other words, if aspirin were given to 100 people after they had a stroke, only 13 of them would not suffer another stroke because they had taken aspirin.
Newer Antiplatelet Agents
Newer antiplatelet agents-dipyridamole plus low-dose aspirin (Aggrenox®), clopidogrel (Plavix®), and ticlopidine (Ticlid®)-though more expensive than aspirin, appear to provide greater protection against secondary strokes, specialists agreed.
There are no head-to-head comparisons among these agents, but three large clinical trials have compared them to aspirin and placebo (no active treatment).
The 2nd European Stroke Prevention Study (ESPS-2) evaluated the combination of dypyridamole and low-dose aspirin (Aggrenox®) in over 6,000 patients who had suffered strokes. The study found that patients taking Aggrenox® had 37% fewer secondary strokes than patients who received placebo, and 22% fewer strokes than patients taking aspirin.
In the Ticlopidine Aspirin Stroke Study (TASS), ticlopidine (Ticlid®) reduced the chances of having a stroke by 21%, however, because some patients have developed an often fatal disorder called thrombotic thrombocytopenic purpura while taking ticlopidine, physicians are often reluctant to prescribe this agent.
In the CAPRIE trial (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events), of 6,400 patients who had suffered a stroke, those who received clopidogrel had about an eight percent reduction in risk for future strokes as patients who received aspirin.
In drawing conclusions from the clinical trials, Dr. Albers asked, "How many events will you actually prevent if you prescribe the more expensive alternative agents? If you follow 1,000 patients for two years, you find that clopidogrel prevents about 10 strokes, ticlopidine prevents about 25, and dipyridamole- aspirin prevents about 30," he concluded.
J. Donald Easton, MD, Professor and Chairman of Clinical Neurosciences at Rhode Island Hospital and Brown University School of Medicine, Providence, said he is a believer in giving patients the best medication, when economically feasible. "If you believe that Aggrenox® or Plavix® are both better than aspirin, then why not use them? Why not go first class?" he stated in a panel discussion. "Stroke is bad business. When it comes to antiplatelet agents and parachutes, you want the very best. For me personally, if I could afford it, I would certainly go for the best agent right from the start."
Dr. Easton also explained that Aggrenox® is considered superior to Plavix® in preventing secondary strokes, but Plavix® may be more beneficial to patients who also have heart disease. Plavix® provides a broader spectrum of vascular protection (preventing heart attacks), though it's not as potent in stroke protection, he explained. Dr. Easton suggested that physicians carefully consider the patient's individual risk factors. The recent availability of new agents that block the blood-clotting action of platelets was the impetus for the American Heart Association (AHA) to revise its recommendations for the prevention of "secondary" strokes. First, the AHA committee evaluated the best dose of aspirin for stroke prevention, and then they compared the benefits of the newer agents to those of aspirin.
As a result of analyzing the data from a number of clinical trials, the AHA committee made the following recommendations:
* As the most cost-effective antiplatelet agent, aspirin is recommended in general as first-line therapy after stroke. However, the alternative agents could be considered reasonable.
* The greatest reduction in risk is seen in patients at the highest risk for stroke (due to risk factors, such as hypertension).
* For patients who cannot take aspirin, clopidogrel is recommended.
* For patients who can take low-dose aspirin, dipyridamole-aspirin is recommended.
* For patients who still have transient ischemic attacks while on aspirin therapy, the recommendation is dypiridamole-aspirin or clopidogrel.
* For patients with atrial fibrillation or similar heart conditions, warfarin is recommended rather than an antiplatelet agent.