Comparison between Ticlopidine, Clopidogrel and Ciostazol in combination with Aspirin in reducing major adverse clinical events, six months after coronary stent implantation: A meta-analysis.

BACKGROUND: Activation of platelets is the major cause of thrombotic occlusion after coronary stenting with restenosis rate occurring 30-50% within the first six months. Oral anti-thrombotic strategies fort lie prevention of sub-acute stent thrombosis in the initial 30 days following cardiac stem insertion demonstrated similar benefit with aspirin in combination with cilostazole and clopidogrel.

OBJECTIVES: To determine the effect of Ticlopidine plus Aspirin (TA), Clopidogrel plus Aspirin (CA), and Cilostazol plus Aspirin (CIA), in reducing the occurrence of major clinical adverse events, six months after coronary stent implantation.

SELECTION CRITERIA: Randomized controlled trials involving patients who underwent successful coronary stenting and were maintained on the mentioned anti-thrombotics.

DATA COLLECTION AND ANALYSIS: We obtained relevant trials from PubMed, Medline, Cochrane, internet electronic databases. We searched abstracts, lists of review articles and retrieved studies by manual and internet search strategies. We included studies regardless of dare and publication.

RESULTS: We gathered 46 trials, narrowed down to 10 studies. Three studies compared TA and CA, and 7 studies compared TA and CIA. TA showed a greater benefit over CA in reducing death and incidence of AMI, RR 1.43, 95% Cl (085, 2.42), RR 1.57, 95% Cl (0.96, 2.55), respectively. However, CIA showed a significant benefit over IA in reducing AMl, death, bleeding complications, and the improvement of diameter stenosis, RR 6.29, 95% Cl (5.82, 6.77). 1-lomogeneity was observed after removal of studies and showed significant benefit with CIA, RR 5.35, 95% Cl (4.67, 6.03).

CONCLUSION: There was a trend towards benefit in using CIA in the reduction of adverse clinical events and significant improvement in diameter stenosis over TIA. On the other hand, TA showed a trend towards benefit over CA in preventing death and AMI. No trials directly compared cilostazol with clopidogrel with long term outcome measurements, which is a limitation of this study.

RECOMMENDATIONS: It is worth pursuing to conduct randomized controlled trials comparing clopidogrel with ticlopidine or cilostazol, which will monitor long term adverse clinical events to be able to demonstrate which antithrombotic will show statistically significant benefit.