Minor Stroke: Combo Therapy vs Aspirin Alone

Mark J. Alberts, MD


September 27, 2013

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Hello. Welcome to this Medscape stroke update. I'm Dr. Mark Alberts, Vice Chair of Neurology at UT Southwestern Medical Center in Dallas.

Today I would like to talk to you about the recently published CHANCE trial[1] in the New England Journal of Medicine, by Wang and colleagues. This study was done in China. The investigators enrolled patients with a very recent transient ischemic attack (TIA) or minor stroke who could be treated within 24 hours of symptom onset. The treatment paradigm was a little bit complicated, so let's walk through it.

One group was given aspirin by itself and various placebos. The intervention group was given aspirin combined with a clopidogrel load of 300 mg, after which they were given combination therapy of aspirin and standard-dose clopidogrel (75 mg/day) for 21 days. After 21 days and up to 90 days, they were given monotherapy with clopidogrel. So it was basically combination therapy (aspirin and clopidogrel) vs aspirin for 21 days, and then up to 90 days it was clopidogrel monotherapy vs aspirin monotherapy. All patients had to be treated within 24 hours of stroke or TIA onset.

The primary endpoint was the occurrence of any stroke, ischemic or hemorrhagic. Secondary endpoints were stroke, myocardial infarction, or vascular death. So, what was found at the end of the study?

Well, they had to screen about 41,000 patients to enroll 5170 patients who met their enrollment criteria. Overall at 90 days, they found an absolute benefit of 3.5% risk reduction for the occurrence of any type of recurrent stroke in the combination group vs aspirin alone. This was highly statistically significant, with a relative risk reduction of about 30% in favor of combination therapy vs monotherapy. For the secondary endpoints of stroke, myocardial infarction, or vascular death, the outcomes were essentially the same, with similar benefits for combination therapy vs aspirin monotherapy.

Another important outcome was safety. In terms of cerebral hemorrhage and systemic hemorrhage, they were essentially the same. They were equivalent between the dual-therapy group and the monotherapy group.

At the end of the day, this was a positive study showing that combination therapy, if given early and for only 21 days, appears to be more effective and as safe as aspirin monotherapy in patients with a TIA or minor stroke.

Obviously, there are a few caveats here. Number one: How well were these patients treated for their other vascular risk factors? The answer is that we are not entirely sure. If you look at some of the supplemental data, you find that only 35% of the patients were taking blood pressure medications, about 40% were taking lipid-lowering medications, and 13% were taking medications for diabetes. These numbers are a little low compared with similar large studies that were done in the United States and Europe. We don't really know about the risk factor profile of the patients in the CHANCE trial because it was not well delineated in the publication. Maybe if those underlying risk factors had been treated more aggressively, the benefit of combination antiplatelet therapy would have been somewhat reduced. We don't know, and it is hard to tell.

What about the CHANCE results compared with results from other large similar trials? The MATCH study[2] that looked at combination therapy did not find any benefit with combination therapy vs monotherapy, but it clearly showed that combination therapy was associated with a higher risk for bleeding. The recently reported SPS3 study[3] also showed that combination therapy did not seem to have any benefits but did increase the risk for bleeding and death.

So, is the CHANCE study the exception that proves the rule, or is it the rule that goes against the exception? It is hard to know at this point. Are we going to change guidelines on the basis of this one study? It is hard to know at this point, because there were some unusual aspects to the study. It does tell us, however, that as acute therapy for a short period of time in a population of Chinese patients, this type of combination therapy appears to be effective and safe -- at least much safer than when used in other studies for a time period of 90 days.

Let's stay tuned. There is the POINT study going on in the United States, sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), that is looking at combination therapy with very early enrollment. Again, it is 90 days of therapy, so we will have to see whether those results are more like MATCH and SPS3 or more like CHANCE.

Thank you for tuning in to this Medscape stroke update. Have a good day.


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