Cilostazol in Addition to Aspirin and Clopidogrel Improves Long-Term Outcomes After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndromes - Cilostazol in Addition to Aspirin and Clopidogrel Improves Long-Term Outcomes After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndromes

Mar 24, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Date Published:
01/01/2009
Date Updated:
03/24/2009
Original Posted Date:
03/24/2009
References

Description:

The goal of the trial was to evaluate treatment with aspirin, clopidogrel, and cilostazol compared with aspirin and clopidogrel in patients with acute coronary syndromes (ACS).

Hypothesis:

Triple therapy with aspirin, clopidogrel, and cilostazol would be more effective in preventing adverse cardiac outcomes after percutaneous coronary intervention (PCI).

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 1,212
Mean Follow Up: 1 year
Mean Patient Age: 60
Female: 27%
Mean Ejection Fraction: 61%

Patient Populations:

  • Patients with an ACS undergoing PCI
  • Patients 20-80 years of age

Exclusions:

  • Contraindication to antiplatelet or anticoagulation medication
  • Pregnancy
  • Planned bypass surgery
  • Acute pulmonary edema, cardiogenic shock, or severe systemic illness
  • Known bleeding disorder
  • Liver disease

Primary Endpoints:

  • Cardiovascular death, MI, stroke, or target vessel revascularization

Secondary Endpoints:

  • Bleeding events

Drug/Procedures Used:

Patients with ACS who underwent PCI were randomized to triple therapy with aspirin, clopidogrel, and cilostazol (n = 604) versus dual therapy with aspirin and clopidogrel (n = 608). Cilostazol was given at a dose of 100 mg twice daily for 6 months.

Concomitant Medications:

At baseline, the use of an angiotensin-converting enzyme inhibitor was 66%, beta-blocker was 81%, and statin was 81%.

All patients received aspirin (300 mg daily for a month, followed by 100 mg daily indefinitely) and clopidogrel (300-600 mg initially, then 75 mg daily for 3-12 months depending on the type of stent that was implanted). Unfractionated heparin (10,000 U) was given prior to the procedure.

Principal Findings:

Overall, 1,212 patients were randomized. The mean age was 60 years, 27% were women, 20% were diabetics, and the mean left ventricular ejection fraction was 61%. The indication for catheterization was unstable angina in 52%, non-ST-elevation myocardial infarction (NSTEMI) in 12%, and STEMI in 36%. Drug-eluting stents were implanted 50% of the time.

At 1 year, the incidence of death, MI, stroke, or target vessel revascularization was 10.3% in the triple therapy group versus 15.1% in the dual therapy group (p = 0.011). Cardiovascular mortality was 1.7% versus 3.3% (p = 0.067), MI was 0.3% versus 0.7% (p = 0.69), stroke was 0.7% versus 1.6% (p = 0.11), and target vessel revascularization was 7.8% versus 10.4% (p = 0.12), respectively for triple versus dual antiplatelet therapy. Benefit appeared to be most pronounced for women and diabetics.

Major bleeding was 0% versus 0.2% (p = 0.5) and minor bleeding was 0.2% versus 0% (p = 0.5), respectively for triple versus dual antiplatelet therapy. There were 2.6% of patients who discontinued cilostazol due to side effects.

Interpretation:

Among patients undergoing PCI for ACS, the use of triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) is beneficial. This regimen reduced major adverse cardiac events at 1 year with all individual outcomes favoring triple therapy. Cilostazol in addition to aspirin and clopidogrel did not appear to increase major or minor bleeding; however, 2.6% of patients discontinued cilostazol due to side effects.

Several trials have now been reported that document the benefit of adding cilostazol to aspirin and clopidogrel. While these results are compelling, they are not definitive. The current study is limited by single-center and open-label design. It is also unknown if the results can be extrapolated to a non-Asian patient population. This topic deserves further study in a multicenter placebo-controlled trial.

References:

Han Y, Li Y, Wang S, et al. Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: a randomized, controlled study. Am Heart J 2009;Mar 12:[Epub ahead of print].

Keywords: Stroke, Acute Coronary Syndrome, Myocardial Infarction, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Ticlopidine, Tetrazoles, Percutaneous Coronary Intervention, Catheterization, Stroke Volume, Diabetes Mellitus


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