Anti-inflammatory Agent, Myocardial Reperfusion Injury, Platelet Aggregation Inhibitors
Conditions
Keywords
Cilostazol, Platelet, Inflammation, Myonecrosis
Brief summary
The purpose of this study is to determine whether adjunctive cilostazol loading/maintenance to standard treatment (aspirin, clopidogrel, and statin) is effective in reduction of major adverse cardiovascular events, platelet activation, inflammation and myonecrosis in patients with non-ST-elevation acute coronary syndrome (ACS)undergoing percutaneous coronary intervention (PCI).
Detailed description
In ACS patients, platelet activation, inflammation, and ischemia-reperfusion injury can be closely associated with the risk of post-PCI myonecrosis and ischemic events occurrence. In the ACCEL-AMI (Adjunctive Cilostazol versus high maintenance-dose ClopidogrEL in patients with Acute Myocardial Infarction)study, adjunctive cilostazol increased platelet inhibition compared with double-dose clopidogrel. Meanwhile, statins can reduce the extent of myonecrosis via limiting inflammation and myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K), ecto-5'-nucleotidase, Akt/endothelial nitric oxide synthase (eNOS), and the downstream effectors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Inhibition of PI3K, adenosine receptors, eNOS, iNOS, or COX-2 abrogates the protective effects of statins. In animal study, the combination of low-dose statin with cilostazol synergistically limits infarct size. Multiple studies have shown that cilostazol can influence inflammation and RISK pathway using the similar pathway with statin. This study will be performed to evaluate the role of adjunctive cilostazol in platelet inhibition, inflammation, and myonecrosis compared with standard treatment.
Interventions
DRUGDual Anti-Platelet Therapy (DAPT)
* Loading: aspirin 300mg + clopidogrel 600mg * Maintenance: aspirin 200mg/d + clopidogrel 75mg/d for 1 month
DRUGTriple Anti-Platelet Therapy (TAPT)
* Loading: cilostazol 200mg + aspirin 300mg + clopidogrel 600mg * Maintenance: cilostazol 100mg bid+ aspirin 200mg/d+ clopidogrel 75mg/d for 1 month
Sponsors
Gyeongsang National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* at least 18 years of age * Non-ST-elevation ACS patients undergoing PCI within 48 hours after hospitalization
Exclusion criteria
* ST segment elevation acute myocardial infarction * NSTE ACS with high-risk features warranting emergency coronary angiography * Oral anticoagulation therapy with warfarin * Use of pre-procedural glycoprotein IIb/IIIa inhibitor * Contraindication to antiplatelet therapy * AST or ALT ≥ 3 times upper normal * Left ventricular ejection fraction \< 30% * WBC \< 3,000/mm3, platelet \< 100,000/mm3 * Creatinine ≥ 3 mg/dl * stroke within 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiovascular events (MACE) | 1 month | Composite of cardiac death, MI and ischemia-driven target lesion revascularization (TLR) |
Secondary
| Measure | Time frame |
|---|---|
| MACE incidence according to P2Y12 reaction unit | 1 month |
| any post-procedural increase of markers of myocardial injury above ULN | 1 month |
| P2Y12 reaction unit levels in the 2 arms | 1 month |
| ACUITY major/minor bleeding rate | 1 month |
| 24hr post-procedural variations from baseline of inflammation markers (IL-6, TNF-alpha, cell adhesion molecules (VCAM, ICAM, E-selectin) | 1 month |
| post-procedural variations from baseline of hs-CRP levels in the 2 arms | 1 month |
Countries
South Korea
Outcome results
None listed