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

• Published in: The American heart journal Vol. 155; no. 6; pp. 1081 - 1089
• Main Authors: Biondi-Zoccai, Giuseppe G.L., MD, Lotrionte, Marzia, MD, Anselmino, Matteo, MD, Moretti, Claudio, MD, Agostoni, Pierfrancesco, MD, Testa, Luca, MD, Abbate, Antonio, MD, Cosgrave, John, MD, Laudito, Antonio, MD, Trevi, Gian Paolo, MD, Sheiban, Imad, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-06-2008; Elsevier; Elsevier Limited
• Subjects: Angioplasty; Angioplasty, Balloon, Coronary; Aspirin; Bias; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Cilostazol; Clinical trials; Coronary Restenosis - drug therapy; Coronary Restenosis - prevention & control; Diseases of the cardiovascular system; Heart attacks; Humans; Hypothesis testing; Medical sciences; Platelet Aggregation Inhibitors - administration & dosage; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Randomized Controlled Trials as Topic; Stents; Studies; Tetrazoles - administration & dosage; Thrombosis; Angioplasty; Evidence-based practice; Coronary artery; Instrumentation therapy; Cardiovascular disease; Systematic review; Cilostazol; Evidence-based medicine; Metaanalysis; Randomization; Clinical trial; Circulatory system; Cardiology
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2007.12.024

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.