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DAPT’s benefit after stroke or TIA clusters in first 21 days

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New POINT analysis confirms 21 days for DAPT

The new model using data from the POINT trial confirms what had been previously shown in the CHANCE trial – that 21 days is a sensible cutoff for dual antiplatelet treatment for patients immediately following a mild stroke or transient ischemic attack. Treatment with dual antiplatelet therapy for 21 days provides the same added benefit as 90 days of treatment but with less excess bleeding. The new findings confirm that the CHANCE results were not specific to a Chinese population.

Dr. Mike Sharma, stroke neurologist, McMaster University, Hamilton, Canada

Dr. Mike Sharma

The new findings also put an added onus on clinicians to start dual antiplatelet therapy very quickly in patients who have had a mild stroke or transient ischemic attack and do not have atrial fibrillation. What was very impressive in the POINT data was the very steep rate of events during the first 48 hours following the index event. We need to revamp our systems again so that these patients are diagnosed and start this treatment as quickly as they did in the trial.

For the time being, clopidogrel is the evidence-based antiplatelet drug to pair with aspirin for this indication. Clopidogrel has the advantages of being generic, cheap, available, and familiar. It’s possible that another P2Y12 inhibitor, such as ticagrelor (Brilinta), might work even better, but that needs to be proven to justify the added expense of a brand-name antiplatelet drug.

Mike Sharma, MD , is a stroke neurologist at McMaster University, Hamilton, Ont. He has been an advisor to Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, and Pfizer. He made these comments in an interview.



– The optimal length for dual antiplatelet therapy in patients who have just had a mild stroke or transient ischemic attack is 21 days, a duration of combined treatment that maximized protection against major ischemic events while minimizing the extra risk for a major hemorrhage, according to a prespecified analysis of data from the POINT trial.

Dr. Jordan J. Elm, biostatistician, Medical University of South Carolina, Charleston Mitchel L. Zoler/MDedge News

Dr. Jordan J. Elm

The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial randomized 4,881 patients with a very recent mild stroke or transient ischemic attack and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, dual antiplatelet therapy (DAPT) cut the incidence of a major ischemic event by a relative 25% but also more than doubled the rate of major hemorrhage (New Engl J Med. 2018 Jul 19;377[3]:215-25).

The new, prespecified analysis looked at outcomes on a week-by-week basis over the course of 90 days of treatment, and showed that during the first 21 days the rate of major ischemic events was 5.6% among patients on aspirin only and 3.6% among those on DAPT, a statistically significant 35% relative cut in these adverse outcomes by using DAPT, Jordan J. Elm, PhD, reported at the World Stroke Congress. During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in both arms of the study, showing that after 3 weeks the incremental benefit from DAPT disappeared, said Dr. Elm, a biostatistician at the Medical University of South Carolina, Charleston.

In contrast, the doubled rate of major hemorrhages (mostly reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment, meaning that limiting DAPT to just 21 days could prevent many of the excess hemorrhages.

“These results suggest that limiting clopidogrel plus aspirin use to 21 days may maximize benefit and reduce risk,” Dr. Elm said, especially in light of the findings confirming the efficacy of 21 days of DAPT following a minor stroke or TIA that had been reported several years ago in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial (New Engl J Med. 2013 Jul 4;369[1]:11-9).

Although the new finding from the POINT results came in a secondary analysis, it’s statistically legitimate and should be taken into account when writing treatment guidelines, she said, emphasizing that “this is a very important analysis that is not just hypothesis generating.”

Another finding from the new analysis was that a large number of major ischemic events, and hence a large number of the events prevented by DAPT, occurred in the first 2 days following the index event, a finding made possible because the POINT investigators enrolled patients and started treatment within 12 hours of the qualifying events.

“It’s better to start treatment early,” Dr. Elm noted, but she also highlighted that major ischemic events continued to accumulate during days 3-21, suggesting that patients could still benefit from DAPT even if treatment did not start until 24 or 48 hours after their index event.

POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm reported no disclosures.

SOURCE: Elm JJ et al. World Stroke Congress, Late-breaking session.

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