The Foundation for Stroke Prevention

A much anticipated clinical study which has taken years to complete was published in the New England Journal of Medicine yesterday. Some people have a small hole known as a patent foramen ovale (PFO) between two chambers of the heart. This defect, although not rare, is recognized as a cause of stroke in some cases. The study, known as CLOSURE I, looked at whether taking medicine such as aspirin was as effective as using a device to close the hole. The conclusion of the study, which included over 900 patients studied for at least two years, was that no difference was found between the two treatments.

As with all medical studies, it is important to understand the details behind the conclusions. The study was undertaken almost ten years ago when new devices appeared to allow closure of a PFO without cardiac surgery, procedures were regularly performed on stroke patients, even though the FDA had not approved those devices for this indication. Once a device is ‘on the market’, it can be used with justification. Since these devices were being widely used in clinical practice, primarily by interventional Cardiologists, it became important to find out whether they were really more effective than medical therapy. It was extremely difficult to find patients that would agree to this study, because the nature of patients is that if a treatment (especially a new, high tech treatment) exists, they would prefer it to being part of a research trial. During the period of this study, approximately 80,000 patients underwent the procedure at an average cost of $10,000. Had insurers not paid for all those procedures, this study would have been completed much earlier, as the only way to have the devices implanted would have been to participate in a research study.

CLOSURE I is highly significant, but another study known as RESPECT has been completed, and the results should become available soon. For now, we can say to most patients with stroke and this cardiac defect that medical therapy is adequate. Whether a group of patients who might benefit from closure can be identified is yet to be resolved.

As always, consultation with an expert in the field is advised. This may include experts in Cardiology and Stroke.

The National Institute of Neurological Disorders and Stroke has stopped a stroke prevention study prior to completion. This is the second study this year which has been halted early by its data safety monitoring board (DSMB). Medical studies have a board which monitors the study to determine whether there are any problems, or whether the preliminary data suggest issues that would make it unethical to continue.
The SPS3 trial is being conducted to learn about preventing a second stroke in patients who have suffered a type of small stroke generally related to hypertension and other factors. The study was designed to test whether two types of interventions would lower the risk of a recurrent stroke; treatment of blood pressure, and use of whether a combination of aspirin and clopidogrel (Plavix) would be better than aspirin alone. Over 3,000 patients were entered into this trial.
The data safety monitoring board suggested that the component of the study related to aspirin and clopidogrel be stopped. Patients on the combination of aspirin and clopidogrel had more bleeding, and did not demonstrate benefit according to the current data.
According to the press release from the NINDS, these results support current guidelines that recommend against the use of the combination of clopidogrel plus aspirin for stroke prevention, and extend this advise to those with small strokes that have been demonstrated by MRI.
What does this mean to clinical practice. It once again demonstrates that the best ways to prevent stroke appear to be the control of risk factors, such as high blood pressure, diabetes, and smoking.

A recently published study suggests that consuming olive oil may prevent stroke in older people. The study, published in the journal Neurology, looked at 7,625 people aged 65 or older in three French cities over a period of five years. After considering diet, physical activity, body mass index and other risk factors for stroke, the study found that those who regularly used olive oil for both cooking and as dressing had a 41 percent lower risk of stroke compared to those who never used olive oil in their diet (1.5 percent in six years compared to 2.6 percent).
In an accompanying editorial, Dr. Nikolaos Scarmeas of Columbia University noted that potentially beneficial effects of olive oil have been noted, including effects on blood glucose, anti-inflammatory effects, and modification of clotting. These may have a role in the reduction of cardiovascular disease, cognitive decline, and now stroke.

It is well known that Coumadin is effective in preventing stroke in patients with atrial fibrillation. But Coumadin (warfarin) is not so easy to use. Dosage is highly variable between patients, diet may affect therapeutic levels, and frequent blood tests are required to keep patients in the correct range of anticoagulation. Now a new class of drugs is emerging which may be useful for preventing stroke.

At the European Society Cardiology meeting in Stockholm this week, a study known as AVERROES was presented. This study used a drug known as apixaban (Pfizer / Bristol-Myers Squibb) compared to aspirin in patients with atrial fibrillation. Patients treated with apixaban had a significantly lower percentage of stroke, without significant increased bleeding.

The newer drugs do not require any monitoring via blood testing, and appear to be effective. Although side effects appear to be minimal, some may become apparent with more widespread use. Apixaban will require twice daily dosing, which may be inconvenient for some patients. A study directly comparing apixaban to warfarin will be completed sometime in 2011.

These drugs usher in a new era in stroke prevention for patients with atrial fibrillation. The first of these drugs may become available in 2011.