Systematic review and meta-analysis of randomized clinical trials appraising the impact of cilostazol after percutaneous coronary intervention

Biondi-Zoccai, Giuseppe G.L.; Lotrionte, Marzia; Anselmino, Matteo; Moretti, Claudio; Agostoni, Pierfrancesco; Testa, Luca; Abbate, Antonio; Cosgrave, John; Laudito, Antonio; Trevi, Gian Paolo; Sheiban, Imad

doi:10.1016/j.ahj.2007.12.024

« Previous Next »American Heart Journal
Volume 155, Issue 6 , Pages 1081-1089, June 2008

Systematic review and meta-analysis of randomized clinical trials appraising the impact of cilostazol after percutaneous coronary intervention

Giuseppe G.L. Biondi-Zoccai, MD
- Division of Cardiology, University of Turin, Turin, Italy
- Reprint requests: Giuseppe Biondi-Zoccai, MD, Interventional Cardiology, Division of Cardiology, University of Turin, S. Giovanni Battista “Molinette” Hospital, Corso Bramante 88-90, 10126 Turin, Italy.
- Dr Biondi-Zoccai has consulted for Boston Scientific (Genoa, Italy), Cordis (Milan, Italy), Invatec, and Mediolanum Cardio Research (Milan, Italy), and has received lecture fees from Bristol Myers Squibb (Rome, Italy). This work is part of a senior investigator project for the Meta-analysis and Evidence-based Medicine Training in Cardiology (METCARDIO) Group, based in Turin, Italy (Protocol #4-2007 at http://www.metcardio.org/protocols.html).
- Both authors equally contributed to this work.
Marzia Lotrionte, MD
- Institute of Cardiology, Catholic University, Rome, Italy
- Both authors equally contributed to this work.
Matteo Anselmino, MD
- Division of Cardiology, University of Turin, Turin, Italy
Claudio Moretti, MD
- Division of Cardiology, University of Turin, Turin, Italy
Pierfrancesco Agostoni, MD
- Antwerp Cardiovascular Institute Middelheim, AZ Middelheim, Antwerp, Belgium
Luca Testa, MD
- Institute of Cardiology, Catholic University, Rome, Italy
Antonio Abbate, MD
- Virginia Commonwealth University Pauley Heart Center, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA
John Cosgrave, MD
- Midland Regional Hospital Mullingar, Mullingar, Ireland
Antonio Laudito, MD
- Division of Cardiac Surgery, University of Turin, Turin, Italy
Gian Paolo Trevi, MD
- Division of Cardiology, University of Turin, Turin, Italy
Imad Sheiban, MD
- Division of Cardiology, University of Turin, Turin, Italy

Received 12 September 2007; accepted 26 December 2007. published online 13 February 2008.

Background

Drug-eluting stents reduce the risk of restenosis after percutaneous coronary intervention (PCI) but may pose a risk of thrombosis. Cilostazol, an oral antiplatelet agent with pleiotropic effects including inhibition of neointimal hyperplasia, could hold the promise of preventing both restenosis and thrombosis. We systematically reviewed randomized clinical trials (RCTs) on the angiographic and clinical impact of cilostazol after PCI.

Methods

We searched RCT in BioMedCentral, CENTRAL, clinicaltrials.gov, EMBASE, and PubMed (November 2007). Coprimary end points were binary angiographic restenosis and repeat revascularization, abstracted and pooled by means of random-effect relative risks (RRs). Small study/publication bias was appraised with multiple methods.

Results

A total of 23 RCTs were included (5428 patients), with median follow-up of 6 months. Pooled analysis showed that cilostazol was associated with statistically significant reductions in binary angiographic restenosis (RR = 0.60 [0.49-0.73], P < .001) and repeat revascularization (RR = 0.69 [0.55-0.86], P = .001). Cilostazol appeared also safe, with no significant increase in the risk of stent thrombosis (RR = 1.35 [0.71-2.57], P = .36) or bleeding (RR = 0.71 [0.43-1.16], P = .17). However, small study bias was evident for both binary restenosis (P < .001) and repeat revascularization (P < .001), suggesting that at least part of the apparent benefits of cilostazol could be due to this type of confounding effect.

Conclusions

Cilostazol appears effective and safe in reducing the risk of restenosis and repeat revascularization after PCI, but available evidence is limited by small study effects. Awaiting larger RCTs, this inexpensive treatment can be envisaged in selected patients in which drug-eluting stents are contraindicated or when there is a need for neointimal hyperplasia inhibition.