A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility.
BACKGROUND
Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke.


RESULTS
A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p<0.01).


CONCLUSIONS
Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy.


BACKGROUND
Controlled-Trials.com ISRCTN83673558.
Sprigg
Nikola
N
Stroke Trials Unit, Institute of Neuroscience, University of Nottingham, Nottinghamshire, United Kingdom.
Gray
Laura J
LJ
England
Tim
T
Willmot
Mark R
MR
Zhao
Lian
L
Sare
Gillian M
GM
Bath
Philip M W
PM
D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D000077144:Clopidogrel; D004176:Dipyridamole / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011674:Pulse; D012449:Safety; D016037:Single-Blind Method; D020521:Stroke / Q000503:physiopathology / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin