1. ORAL CILOSTAZOL TREATMENT PREVENTS RESTENOSIS AND MAJOR ADVERSE CLINICAL EVENTS AFTER DRUG-ELUTING STENT IMPLANTATION: EVIDENCE FROM A META-ANALYSIS
G. Biondi-Zoccai,1 C. Moretti,1 F. Sciuto,1 P. Omedé,1 C. La Spina,1 V. Infantino,1 E. Cavallero,1 E. Giraudi,1 E. Menditto,1 C. Iacovino,1 F. Colombo,1 P. Agostoni,2 A. Abbate,3 M. Bollati,1 I. Sheiban1
1University of Turin, Turin, Italy AZ Middelheim, Antwerp, Belgium; 3Virginia Commonwealth University, Virginia, USA

2. BACKGROUND
Drug-eluting stents (DES) reduce in-stent neointimal hyperplasia, but restenosis, repeat revascularization and stent thrombosis still remain a concern in several high-risk patients.
Cilostazol, an oral antiplatelet agent with pleiotropic effects including inhibition of neointimal hyperplasia which is already FDA approved for the treatment of claudication, could hold the promise of further inhibiting restenosis and prevent thrombosis.

3. OBJECTIVES
We systematically reviewed randomized clinical trials (RCT) on the impact of cilostazol after PCI with DES implantation.
Our goal was specifically to pool major outcomes from included studies with meta-analytic techniques.

4. METHODS
We searched Bio-MedCentral, CENTRAL, clinicaltrials.gov, EMBASE, and PubMed for randomized trials comparing cilostazol vs control after PCI (keywords: cilostazol, coronary, and restenosis; updated March 2008).
Inclusion criteria were: (a) randomized allocation, (b) comparison of cilostazol vs control, (c) after PCI with DES, and (d) follow-up ≥1 month.
Exclusion criteria were: (a) duplicate reports, (b) lack of outcome data beyond hospitalization, and (c) equivocal or nonrandom treatment allocation.

5. METHODS
The primary angiographic end-point was binary restenosis at 6 months of follow-up.
The primary clinical end-point was the rate of major adverse cardiac events (MACE), ie the composite of death, myocardial infarction (MI) or repeat target vessel/lesion revascularization (TVR/TLR) at 6-9 months.

6. INCLUDED STUDIES Study Year Pts on cilostazol Pts on control Rx CIDES
2008
113
124
DECLARE-Diabetes
200
DECLARE-Long
2007
250
OPTIMUS-2 13 12

7. RESULTS
A total of 4 RCTs were included (1,205 patients), with median follow-up of 6 months.
Pooled analysis showed that cilostazol was associated with statistically significant reductions in binary angiographic restenosis (RR=0.53 [ ], p=0.001), as well as target lesion revascularization (RR=0.41 [ ], p=0.0008).

8. RESULTS
These benefits on restenosis and lead to significant benefits of cilostazol on the occurrence of MACE (RR=0.43 [ ], p=0.0008).
Cilostazol appeared also safe, with no significant increase in the risk of death (RR=0.67 [ ], p=0.66), stent thrombosis (RR=0.74 [ ], p=0.71), or bleeding (RR=0.71 [ ], p=0.56).

9. RISK OF BINARY RESTENOSIS
RISK OF TLR

10. RISK OF TVR
RISK OF MACE

11. RISK OF DEATH
RISK OF MI

12. RISK OF STENT THROMBOSIS
RISK OF BLEEDING

13. FUNNEL PLOT FOR MACE

14. CONCLUSIONS
Cilostazol appears effective and safe in reducing the risk of restenosis, repeat revascularization and major adverse cardiac events after PCI with DES.
Awaiting larger RCTs, this inexpensive treatment can be envisaged in selected patients deemed at high-risk of restenosis despite being treated with DES, such as diabetics, those with chronic renal failure, small vessel disease or bifurcation lesions.

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