Neurology Today Conference Reporter: International Stroke Conference
Access daily, concise peer-reviewed reports from the International Stroke Conference selected by the Neurology Today editors.

Monday, February 27, 2017

Adding Third Antiplatelet Did Not Prevent Strokes and Increased Bleeding Risks

BY ED SUSMAN

HOUSTON—The addition of a third antiplatelet drug did nothing to prevent strokes, but it did increase bleeding risks, researchers reported here Thursday at the 2017 International Stroke Conference sponsored by the American Heart Association/American Stroke Association.

The TARDIS (Triple Antiplatelets for Reducing Dependency in Ischaemic Stroke) study was an international, prospective, randomized open-label blinded-endpoint controlled trial. Patients with acute non-cardioembolic ischemic stroke or transient ischemic attack (TIA) were randomized to intensive antiplatelet therapy (combined aspirin, clopidogrel and dipyridamole) or guideline-recommended antiplatelets (clopidogrel alone, or combined aspirin and dipyridamole) for one month. The primary outcome was stroke and TIA recurrence, and their severity (as measured by the modified Rankin Scale) at three months.

The researchers reported that intensive therapy with aspirin, clopidogrel, and dipyridamole had similar outcomes as less intensive therapy at 90 days in terms of stroke or TIA recurrence and severity on the modified Rankin Scale, said the study leader Philip Bath, MBBS, MD, head of clinical neuroscience at the University of Nottingham in the United Kingdom (UK).

When compared with UK guideline recommendations for one or two antiplatelets, the use of a three-drug combination did not significantly reduce the risk of stroke or transient ischemic attacks (adjusted hazard ratio 0.90 [95% CI 0.69-1.19] p=0.47).

"Any serious adverse events were also similar in both the guideline-driven treatment and the intensive treatment patients, but there were more severe bleeding episodes with intensified therapy," Dr. Bath said. The risk of bleeding was more than two times greater if the patients were on the intensified therapy rather than on the guideline-driven treatment (p<0.001). Fatal bleeding was also greater numerically, but was low overall. There were seven fatal bleeding episodes in the intensive group and four in the guideline-driven treatment.

"Any tendency for less recurrent cerebral ischemic events were offset by increases in major bleeding with more intensive treatment," Dr. Bath said. He said that the TARDIS study would not change clinical practice. "Intensive antiplatelet therapy is not recommended," he said, suggesting instead that clinicians "use the guideline therapy of either clopidogrel or aspirin plus dipyridamole."

Amytis Towfighi, MD, director of neurological services and innovation for the Los Angeles County Department of Health Services, who moderated the session, said that an ongoing trial in the United States is studying the same treatment choices and may provide a definitive word on whether added therapies are beneficial or not.

"Only one trial in the US has shown a benefit for dual antiplatelet therapy, and that is why we are waiting for the results of the POINT [Platelet-Oriented Inhibition in New TIA] trial," Dr. Towfighi said. "That is [also] why the US guidelines now recommend single antiplatelet therapy to prevent recurrent stroke. Aspirin and dipyridamole are packaged together in one pill, so it is two drugs in one pill, and we count it as one pill."

Because there have been trials using dual antiplatelet treatment in people with stents, which showed an anti-stroke benefit, "the stroke community thinks that two is better than one for stroke prevention," she said. "But that trial has never been done."

"We really don't know if two [antiplatelets] are better than one [for stroke prevention]," she said. "Considering the TARDIS results, however, we should not be looking at three drugs." ​

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