Comparative stroke recurrence, higher bleeding risk with intensive antiplatelet therapy
Intensive (triple) antiplatelet therapy does not affect the recurrence of ischaemic stroke or transient ischaemic attack (TIA) compared with guideline standard-of-care antiplatelet therapy, but increases the risk of bleeding, according to interim data from the TARDIS* trial presented at the International Stroke Conference 2017 (ISC 2017) in Houston, Texas.
Between April 2009 and March 2016, researchers of this prospective, open-label trial enrolled 3,096 patients (mean age, 69 years, 62.8 percent male) from 106 sites in four countries (United Kingdom, Georgia, Denmark, and New Zealand). Patients were recruited within 48 hours of a noncardioembolic stroke (69.2 percent) or TIA (30.8 percent) and were randomized to either intensive (aspirin + clopidogrel + dipyridamole) or standard-of-care guideline therapy (aspirin + dipyridamole, or clopidogrel alone) for 30 days.
Dosing of the antiplatelet treatments was as follows: aspirin (300 mg loading dose followed by 75 mg once/daily from days 1–30), clopidogrel (300 mg loading dose followed by 75 mg once/daily from days 1–30), and dipyridamole (200 mg twice/daily from days 1–28/30 or 150 mg thrice/daily from days 1–30).
There was no difference in the incidence of ordinal stroke or TIA between patients on intensive or guideline therapy (odds ratio [OR], 0.93; 2p=0.61). Incidence of fatal stroke was also comparable between intensive and guideline therapy (OR, 1.62; 2p=0.29). [ISC 2017, abstract LB4]
However, there was an increase in the number and severity of bleeding events among patients on intensive therapy (OR, 2.49; 2p<0.001 for ordinal bleeding, OR, 2.04; 2p=0.013 for major bleeding, and OR, 3.33; 2p=0.037 for fatal or major intracerebral haemorrhage).
“Overall, there was no benefit in giving three drugs over two or one,” said study principal investigator Professor Philip Bath from the University of Nottingham, Nottingham, UK.
The TARDIS trial was considered neutral overall, as there was no difference pertaining to the total number of deaths, strokes, myocardial infarction, and major bleeding events, said the researchers.
“The overall net risk-benefit was not different ... We cannot recommend taking intensive antiplatelet [therapy]. We should stick to current guidelines,” said Bath.
“[TARDIS] was a well-done study and the results are consistent with prior studies showing that more blood thinning is not necessarily better,” said Dr Mark Alberts, Chief of Neurology at Hartford Hospital, Hartford, Connecticut, US, who represented the American Stroke Association at the press briefing.
“We have seen this with numerous other studies of antiplatelet therapy both for ischaemic stroke as well as coronary artery disease that the more antiplatelet agents you add on and the longer the treatment, the [higher] the risk of haemorrhagic or bleeding complications, not just in the brain but throughout the body such as gastrointestinal haemorrhage,” he said.
Studies to identify the subgroup of patients who are at very high risk for recurrent ischaemic events and to determine the length of intensive therapy are currently underway, said Alberts, referring to the ongoing POINT** trial in the US.