After a stroke: Does treatment with dipyridamole and ASA have a benefit?

A combination therapy of dipyridamole and ASA has more adverse effects than clopidogrel or ASA alone. It is not proven that the combination drug has benefits over clopidogrel or ASA alone.

A stroke happens when parts of the brain are not supplied with enough oxygen anymore. This is often caused by a blood vessel in the brain being blocked. The medical name for this is ischemic stroke (ischemia = insufficient blood supply). A stroke can have different symptoms including paralysis or problems speaking or swallowing. To read more about the signs of a stroke click here.

A blocked blood vessel can have different causes. Changes in the wall of the blood vessel can lead to a blockage, for example. These changes in the blood vessels are called arteriosclerosis. A vessel can also become blocked by a blood clot that has occurred in another part of the body. Such a blood clot can travel through the bloodstream to the brain and block one of its vessels. About 8 out of 10 strokes are ischemic strokes, which are mostly caused by a blocked vessel in the brain (80%).

Another cause of strokes, which occurs less frequently, is bleeding in the brain. Bleeding can occur if the wall of a blood vessel in the brain is damaged and blood enters the tissue, for example. This information only deals with ischemic strokes. Strokes caused by bleeding in the brain are treated differently.

After a stroke: What you can do to prevent further problems

People who have had a stroke have a higher risk of getting another stroke. About 40 out of 100 people who have survived an ischemic stroke get another stroke within the following 10 years (40%). The risk is particularly high during the first 6 months. Other cardiovascular diseases like heart attacks are also more frequent when someone has already had a stroke.

There are several things that can be done to prevent new strokes or cardiovascular diseases. These include avoiding certain risks, for example by giving up smoking or reducing overweight. Regularly taking anti-clotting medication can also reduce the risk of other cardiovascular diseases. These medications are also commonly called “blood thinners”.

There are several kinds of anti-clotting medication, including anticoagulants and antiplatelets. Anticoagulants are drugs used in people who have a particularly high risk of stroke. These often include people with atrial fibrillation – a certain type of heart rhythm problems – or with artificial heart valves.

However, the anticoagulants that are most commonly used in people who have had a heart attack or a stroke are antiplatelets. This information is only about the effect of antiplatelets. You can read more about blood clotting in general here.

Antiplatelets: several options to choose from

The most commonly used antiplatelets are drugs with the agent acetylsalicylic acid (ASA, or ASS in German). There has been a lot of experience using ASA and it is known to be able to reduce the risk of complications of a stroke. Another antiplatelet is clopidogrel. You can read more about this agent here.

Antiplatelets can have adverse effects too, particularly bleedings. Light bleedings, as with nose bleeds, are usually not a problem. But there can also be serious adverse effects such as heavy bleeding in the stomach and bowel, which need urgent medical treatment. You can read more about how to use anti-clotting medications safely here.

Another antiplatelet medication has been available for some time that can be used to prevent cardiovascular diseases after a stroke: dipyridamole. In Germany, this agent is only approved for use in combination with ASA. The trade name of this combination drug is Aggrenox®. The German Institute for Quality and Efficiency in Health Care (IQWiG) – the publisher of this website – has looked into the advantages and disadvantages of this product.

Trials on the combination of dipyridamole and ASA

In cooperation with researchers in Germany from the University of Bremen and the Institute for Pharmacology at the Klinikum Bremen-Mitte, IQWiG has assessed trials on treatment with dipyridamole and ASA after a stroke. The researchers only evaluated so-called randomized controlled trials because these provide the most conclusive results. You can find out how this kind of trial is done here.

In a thorough search, the researchers found a total of 6 trials. Three of these trials tested short-term treatment with the combination drug after a stroke over a period of up to 30 days. But these trials only included a total of about 700 people.

The other 3 trials tested long-term treatment with dipyridamole and ASA over a period of up to 4.5 years. Over 28,000 people participated in these trials. The combination therapy was compared to either treatment with clopidogrel, with ASA alone, or with a placebo (a fake medication).

Conclusions: Poor results for combination drug

Short-term treatment with dipyridamole and ASA: benefit not clear, greater harm proven

The trials on short-term treatment could not show a benefit of a combination of dipyridamole and ASA. They did not make further strokes or heart attacks any more unlikely and did not lead to fewer people dying than the treatments the combination was compared with, either.

A clear result was found regarding adverse effects: dipyridamole plus ASA had worse results than ASA alone. Adverse effects like headaches, nausea or vomiting were more frequent in participants who took the combination drug. People who took the combination drug also ended the treatment more often than people who took ASA alone.

Long-term treatment with dipyridamole and ASA: No advantages over clopidogrel or ASA alone, but more adverse effects

The trials on long-term treatment did not show any advantages of the combination drug over the other antiplatelets, that is clopidogrel or ASA alone. But adverse effects and complications were more frequent in dipyridamole and ASA, also in comparison to clopidogrel or ASA alone. 38 out of 1000 people who took dipyridamole plus ASA had severe bleeding (3.8%) – while this was the case in 34 out of 1000 people who took ASA or clopidogrel (3.4%). Severe bleeding includes bleeding that can occur in the brain and lead to loss of vision or even to death. People who took the combination drug also stopped treatment more often.

Overall the evaluation of the trials showed that there was no advantage for the combination of dipyridamole and ASA over clopidogrel or ASA alone, neither in short-term nor long-term treatment. But the combination drug more commonly had adverse effects or complications.

Author: German Institute for Quality and Efficiency in Health Care (IQWiG)

Note

This health information is a summary of a scientific report published by IQWiG. It is not an assessment of the right to have health care services reimbursed by statutory health insurance funds in Germany. By law, decisions about the reimbursement of diagnostic and therapeutic procedures can only be made by the German Federal Joint Committee (G-BA). The Federal Joint Committee takes IQWiG reports into consideration in its decision-making process. You can find information about the decisions of the German Federal Joint Committee on its English-language website, www.english.g-ba.de.

© IQWiG (Institute for Quality and Efficiency in Health Care)