Evaluation of antiplatelet agents for secondary prevention of stroke using mixed treatment comparison meta-analysis

The current guidelines recommend various antiplatelet agents used alone or in combination for secondary prevention of noncardioembolic stroke.

The purpose of this study was to conduct a mixed treatment comparison meta-analysis to determine which antiplatelet or combination of antiplatelet agents is most efficacious and tolerable in patients with prior stroke.

A comprehensive literature search was conducted in MEDLINE (1945 through March 2012), EMBASE (1974 through March 2012), and the Cochrane Controlled Trials Registry (1975 through April 2012) to identify randomized trials evaluating the role of various antiplatelet agents and combinations for the secondary prevention of stroke. Key articles were cross-referenced for additional studies. Data were screened and evaluated to generate direct and indirect comparisons for recurrent stroke and overall hemorrhagic events. Data were reported as rate ratios (RRs) and 95% CIs.

A total of 24 articles were included in the analysis. Eleven antiplatelet regimens were compared in >88,000 patients. The combination of acetylsalicylic acid (ASA) plus dipyridamole (DP) was more protective against recurrent stroke than ASA alone (RR = 0.78; 95% CI, 0.64-0.93), and no differences were found in all other direct and indirect comparisons with active treatment. ASA plus DP was associated with more overall hemorrhagic events than DP (RR = 1.83; 95% CI, 1.17-2.81), cilostazol (RR = 2.12; 95% CI, 1.21-3.48), and triflusal (RR = 1.67; 95% CI, 1.05-2.78) but fewer events than the combination of ASA plus clopidogrel (RR = 0.38; 95% CI, 0.25-0.56). The combination of ASA plus clopidogrel was associated with an excess of overall hemorrhagic events compared with clopidogrel (RR = 2.81; 95% CI, 1.96-4.10), cilostazol (RR = 5.56; 95% CI, 3.03-9.66), DP (RR = 4.78; 95% CI, 2.80-8.21), sarpogrelate (RR = 3.59; 95% CI, 1.96-6.45), terutroban (RR = 2.13; 95% CI, 1.21-3.61), ticlopidine (RR = 2.80; 95% CI, 1.69-5.00), and triflusal (RR = 4.36; 95% CI, 2.62-7.81).

We found that ASA plus DP was more protective than ASA alone for preventing recurrent stroke; however, no difference was found between most direct and indirect comparisons of antiplatelet agents and combinations. More overall hemorrhagic events seemed to occur with the combination of ASA and clopidogrel than with other treatments. Selection of antiplatelet therapy for the secondary prevention of stroke must be individualized according to patient comorbidities, including risk of stroke recurrence and bleeding.