Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With AMI - ACCEL-AMI

Feb 20, 2010
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Trial Sponsor:
Research Foundation of Gyeongsang National University Hospital
Date Published:
01/01/2010
Date Updated:
02/20/2010
Original Posted Date:
02/20/2010
References

Description:

The goal of the trial was to evaluate three regimens of antiplatelet therapy after stenting for acute myocardial infarction (AMI): 1) cilostazol plus standard-dose clopidogrel, 2) high-dose clopidogrel, or 3) standard-dose clopidogrel.

Hypothesis:

Cilostazol plus standard-dose clopidogrel would be more effective at achieving high platelet inhibition.

Study Design

Study Design:

Patients Screened: 120
Patients Enrolled: 90
Mean Follow Up: 30 days
Mean Patient Age: 61 years
Female: 30%
Mean Ejection Fraction: Mean 56%

Patient Populations:

  • Patients at least 18 years of age who underwent stenting for STEMI or non-STEMI

Exclusions:

  • Active bleeding or bleeding disorder
  • Anticoagulation therapy with warfarin
  • Left ventricular ejection fraction <30%
  • Thrombocytopenia (<100,000/mm3)
  • Leukopenia (<3000/mm3)
  • Liver enzymes >3 times the upper limit of normal
  • Serum creatinine >2.5 mg/dl
  • Limited life expectancy

Primary Endpoints:

  • Inhibition of maximal platelet aggregation between predischarge and 30 days
  • Aggregation determined by light transmittance aggregometry and the VerifyNow P2Y12 assay

Secondary Endpoints:

  • Inhibition of late platelet aggregation
  • Percent change in P2Y12 reaction unit
  • Adverse outcomes

Drug/Procedures Used:

After stenting for AMI, patients were randomized to: 1) cilostazol 100 mg twice daily plus clopidogrel 75 mg daily (n = 30), 2) clopidogrel 150 mg daily (n = 30), or 3) clopidogrel 75 mg daily (n = 30).

Patients underwent platelet reactivity assessment prior to discharge.

Concomitant Medications:

In the emergency department, all patients received clopidogrel 600 mg and aspirin (300 mg load then 200 mg daily). Percutaneous coronary intervention was performed with unfractionated heparin or low molecular weight heparin.

Principal Findings:

Overall, 90 patients were randomized. There was no difference in baseline characteristics between the groups. In the cilostazol plus standard-dose clopidogrel group, the mean age was 61 years, 30% were women, clinical presentation was ST-elevation myocardial infarction (STEMI) in 47%, mean body mass index was 24 kg/m2, 30% had diabetes, and mean left ventricular ejection fraction was 56%.

At 30-day follow-up, inhibition of maximal platelet aggregation was 42.4% in the cilostazol plus standard-dose clopidogrel group, 19.1% in the high-dose clopidogrel group, and 6.0% in the standard-dose clopidogrel group (p < 0.001).

Inhibition of late platelet aggregation was 66.4%, 38.1%, and 10.8% (p < 0.001) and percent change in P2Y12 reaction unit was 43.0%, 30.7%, and 10.6% (p < 0.001), respectively for cilostazol plus standard-dose clopidogrel, high-dose clopidogrel, and standard-dose clopidogrel.

No patient discontinued study medication during the follow-up period and there were no adverse events or major bleeding in any group.

Interpretation:

After STEMI or non-STEMI patients were treated with stents, there was greater platelet inhibition with cilostazol plus standard-dose clopidogrel, compared with high-dose or standard-dose clopidogrel. In this small study, cilostazol appeared to be well tolerated.

Since recurrent adverse cardiac events are not infrequent after MI, the addition of cilostazol to aspirin and clopidogrel may help improve outcomes; however, only a randomized clinical trial powered for clinical events can answer this question. Additionally, the effect of cilostazol will need to be considered along side of newer agents such as prasugrel and ticagrelor.

References:

Jeong YH, Hwang JY, Kim IS, et al. Adding cilostazol to dual antiplatelet therapy achieves greater platelet inhibition than high maintenance dose clopidogrel in patients with acute myocardial infarction: results of the Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With AMI (ACCEL-AMI) Study. Circ Cardiovasc Interv 2010;3:17-26.

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Thiophenes, Coronary Disease, Ticlopidine, Piperazines, Tetrazoles, Stents, Body Mass Index, Platelet Aggregation, Stroke Volume, Diabetes Mellitus


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