Intensive antiplatelet therapy did not significantly reduce the risk of recurrent stroke or transient ischemic attack (TIA), according to clinical trial results presented at the 2017 International Stroke Conference in Houston, Texas.
The Triple Antiplatelets for Reducing Dependency in Ischemic Stroke (TARDIS) trial is an international, prospective, randomized open-label blinded end point-controlled trial conducted in 4 countries at 106 sites with more than 3000 patients (average age, 69 years). Of these 3096 patients, 2143 had ischemic stroke and 953 had TIAs. Patients were randomly assigned to receive either guideline-based antiplatelet therapy or intensive antiplatelet therapy.
Intensive or triple antiplatelet therapy included aspirin, clopidogrel, and dipyridamole. The current UK guidelines recommend aspirin plus dipyridamole or clopidogrel alone. In TARDIS, the patients assigned to triple antiplatelet therapy were given a loading dose of aspirin (300 mg) and then 51 to 150 mg/d (days 1 to 30); a loading dose of clopidogrel (300 mg) and then 75 mg/d (days 1 to 30); and dipyridamole 225 to 450 mg in divided doses twice daily (as 200 mg extended-release capsules twice daily or as tablets 3 to 4 times daily).
The primary efficacy end point was designated as stroke/TIA severity as assessed by modified Rankin Scale (mRS). Secondary outcomes included safety (severity of bleeding), death, and vascular events by severity, as well as dependency, disability, quality of life, mood, cognition, and institutionalization.
In March 2016, the Data Monitoring Committee recommended that the trial be stopped and recruitment was halted in April 2016; therefore, the data presented are interim until the investigators have completed scan adjudication and database validation.
Among patients who were assigned to intensive antiplatelet therapy, 0.8% (n=13) had a fatal stroke compared with 0.5% (n=8) of patients in the guideline therapy group (mRS 6) at 90 days. The adjusted common odds ratio (acOR) for stroke/TIA was 0.93 (P =.61) and for fatal stroke was 1.62 (P =.29).
Meanwhile, the acOR for ordinal bleeding was 2.49 (P <.001), and fatal bleeding had an adjusted hazard ratio (aHR) of 2.32 (P =.20). The aHR for major bleeding at 90 days was 2.04 (P =.013), fatal/major intracranial bleeding was 3.33 (P =.037), and fatal/major extracranial bleeding was 1.76 (P =.092).
There were no significant differences in total number of deaths, strokes, myocardial infarctions, or major bleeds between the 2 treatment arms.
As a result of these findings, the researchers advised against intensive antiplatelet therapy for patients with ischemic stroke to prevent recurrent stroke or TIA.
Bath PM, Woodhouse LJ, Flaherty K, Havard D, England TJ, Sprigg N. Intensive vs guideline antiplatelet therapy for preventing recurrence in patients with acute ischemic stroke or TIA: main results from the Triple Antiplatelets for Reducing Dependency in Ischemic Stroke (TARDIS) trial. LB4. Presented at: the 2017 International Stroke Conference. February 22-24, 2017: Houston, TX.