What Is the Optimal Number of Antiplatelet Agents for Preventing Recurrent Stroke?

HOUSTON—Although dual antiplatelet therapy provides a greater reduction in the risk of recurrent stroke than does antiplatelet monotherapy, adding a third agent may not increase the benefit, according to research presented at the International Stroke Conference 2017. Administering three antiplatelet agents does, however, increase the risk of bleeding, compared with dual antiplatelet therapy.

In 2012 and 2013, literature reviews suggested that the risk of recurrent stroke was reduced among patients who received two antiplatelet agents, compared with patients who received a single antiplatelet agent. These analyses prompted the question of whether triple antiplatelet therapy would provide a further risk reduction.

To examine this question, Philip Bath, MD, Chair of the Division of Clinical Neuroscience at the University of Nottingham, United Kingdom, and colleagues designed the Triple Antiplatelets for Reducing Dependency After Ischemic Stroke (TARDIS) trial. The researchers randomized patients with acute ischemic stroke or transient ischemic attack (TIA) to intensive therapy (ie, triple antiplatelet therapy) or standard of care (ie, dual antiplatelet therapy) for one month. After 30 days, all patients received standard of care. The study’s primary outcome was recurrent stroke or TIA at 90 days. Eligible patients entered the study within 48 hours of their index event, and patients with any level of stroke severity were accepted.

Philip Bath, MD

The investigators administered aspirin, clopidogrel, and dipyridamole to participants at standard doses. At the beginning of the trial, UK guidelines recommended the combination of aspirin and dipyridamole as first-line treatment for prevention of recurrent stroke. In 2010, the National Institute for Health and Care Excellence changed the guideline to recommend clopidogrel alone as first-line treatment. Dr. Bath and colleagues changed the treatment given to their standard-of-care group accordingly.

The researchers intended to enroll 4,100 participants, but ended the trial early on the recommendation of the data-monitoring committee. In all, 3,096 patients were enrolled. Their average age was 69. Approximately 63% of the population was male. The average time of stroke or TIA onset was 29 hours before enrollment. About one-third of patients had been taking antiplatelet therapy at baseline.

Dr. Bath and colleagues found no difference in the rate of recurrent stroke or TIA between treatment groups. Subgroup analysis found that people with an NIH Stroke Scale (NIHSS) score of 3 or lower at baseline tended to benefit from intensive therapy. Standard of care, however, tended to be superior for patients with an NIHSS score greater than 3. In addition, intensive therapy tended to be superior to the combination of aspirin and dipyridamole, but inferior to clopidogrel. Intensive therapy also was associated with significantly more bleeding and more severe bleeding.

—Erik Greb

Suggested Reading

Geeganage CM, Diener HC, Algra A, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012;43(4):1058-1066.

TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). Int J Stroke. 2015;10(7):1159-1165.

Wong KS, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013;128(15):1656-1666.