Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet therapy for patients undergoing PCI: a meta-analysis of randomized trials with adjusted indirect comparisons

Abstract

Objective:

To assess the long-term clinical efficacy and safety of adding cilostazol to aspirin plus clopidogrel (triple antiplatelet therapy, TAT) in patients undergoing percutaneous coronary intervention (PCI) and explore its role in the era of new generation adenosine diphosphate (ADP)-receptor antagonists.

Methods:

PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) comparing TAT versus dual antiplatelet therapy (DAT), followed by a manual search. Then, a meta-analysis of RCTs comparing TAT versus standard DAT in patients undergoing PCI was performed. Furthermore, indirect comparisons of TAT versus new generation ADP-receptor antagonist based DAT (prasugrel or ticagrelor based DAT) were undertaken, with standard DAT as a common comparator. The included end-points were major adverse cardiovascular event (MACE), target lesion revascularization (TLR), target vessel revascularization (TVR), death, myocardial infarction (MI), stent thrombosis, bleeding and other drug adverse events.

Results:

Twelve RCTs with a total of 31,789 patients were included. Compared with standard DAT (n = 2551), TAT (n = 2545) significantly reduced the incidence of MACE (OR: 0.56, 95% CI: 0.47–0.68, P < 0.00001), TLR (OR: 0.51, 95% CI: 0.34–0.75, P = 0.0006) and TVR (OR: 0.59, 95% CI: 0.46-0.75, P < 0.0001), and did not change significantly in death (OR: 0.68, 95% CI: 0.44–1.05, P = 0.08), MI (OR: 0.80, 95% CI: 0.45–1.44, P = 0.46), stent thrombosis (OR: 0.61, 95% CI: 0.27–1.36, P = 0.23), major bleeding (OR: 1.42, 95% CI: 0.52–3.85, P = 0.49) and overall bleeding (OR: 1.16, 95% CI: 0.79–1.69, P = 0.45). Compared with prasugrel (n = 6813) or ticagrelor based DAT (n = 6732), TAT (n = 2545) further reduced the incidence of MACE (OR: 0.80, 95% CI: 0.72–0.90, P = 0.0012; OR: 0.83, 95% CI: 0.75–0.92, P = 0.0003, respectively).

Conclusions:

Compared with standard DAT, the long-term use of TAT in patients with PCI gives more benefits in reducing the incidence of MACE, TLR and TVR without increasing bleeding. Furthermore, it might be superior to prasugrel or ticagrelor based DAT in term of MACE, which needs to be confirmed by future studies with direct comparisons.

Keywords::

• Cilostazol
• Indirect comparison
• Meta-analysis
• Percutaneous coronary intervention
• Triple antiplatelet therapy

Transparency

Declaration of funding

This work was supported by National Natural Science Foundation of China (No. 81170125, 81270209), the Science and Technology Commission of Shanghai Municipality (No. 12JC1406400, 10ZR1420400), and the Doctor Innovation Fund of Shanghai Jiaotong University School of Medicine (BXJ201224). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author contributions: Protocol conception and design: Y.Z., Y.C. Selection and screening of trials included in the analysis: Y.C., Y.T. Data extraction and analysis: Y.C., Y.T., Y.Z. Writing paper: Y.C., Y.Z. Manuscript revision: Y.X., X.H., Y.Z.

Declaration of financial/other relationships

Y.C., Y.Z., Y.T., X.H., and Y.X. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.