Coronary Interventions Antiplatelet-based Only - CIAO

Description:

The goal of this trial was to evaluate the performance of percutaneous coronary intervention (PCI) with heparin compared to without heparin among patients with stable angina undergoing elective PCI for non-complex lesions.

Hypothesis:

PCI without heparin will be non-inferior to PCI with heparin in patients with stable angina, in terms of both safety and efficacy.

Study Design

Study Design:

Patients Enrolled: 700
Mean Follow Up: 30 days
Mean Patient Age: 62.9 years
Female: 21
Mean Ejection Fraction: 53.4%

Patient Populations:

  • Located in a native coronary artery segment >2.5 mm in diameter
  • >70% stenosis
  • <33 mm in length
  • Non-calcified
  • Without important side branches
  • Non-ostial, non-left main
  • Free of visible thrombus
  • No chronic occlusion

Exclusions:

  • Acute coronary syndromes
  • MI within 2 weeks
  • Age >90 years
  • Received unfractionated heparin within 12 hours, low molecular weight heparin within 24 hours, or warfarin within 3 days
  • International normalized ratio >1.3
  • An indication for long-term anticoagulation
  • Contraindication to aspirin and/or thienopyridines

Primary Endpoints:

MACE: Composite of death, acute MI, or need for urgent vessel revascularization occurring within 30 days of the index procedure

Secondary Endpoints:

Bleeding complications

Drug/Procedures Used:

Patients at a single center were randomized to PCI with heparin (70-100 IU/kg, goal activated clotting time [ACT] <250 seconds) or placebo (saline). Heparin (7.5 IU/ml) could be used in both groups to flush the catheters.

Concomitant Medications:

Aspirin (75-160 mg/day) plus ticlopidine (250 mg twice daily) or clopidogrel (75 mg/day) for 7 days prior to the procedure or a 300 mg clopidogrel loading dose 24 hours prior to the procedure. None of the patients in either of the groups received glycoprotein IIb/IIIa inhibitors.

Principal Findings:

A total of 350 patients were randomized to each arm. Baseline characteristics were fairly similar between the two arms, except for the incidence of non–insulin-dependent diabetes, which was higher in the control arm. Bare-metal stents were used in 45.2% of patients. The mean number of stents per patient was 1.1. Mean procedure time was 11.5 minutes in the heparin group and 10.7 minutes in the placebo group. Mean peak ACT was 201 seconds and 127 seconds, respectively.

Safety: The primary endpoint of major adverse cardiac events (MACE) at 30 days was similar between the heparin and the control arms (3.7% vs. 2.0%, p = 0.17, p < 0.0001 for non-inferiority). Similarly, the rates of myocardial infarction (MI) (3.1% vs. 2.0%, p = 0.34) and urgent lesion revascularization (0.6% vs. 0.3%, p = 1.0) at 30 days were also similar between the two arms. There were no deaths at 30 days in either of the arms. There were no cases of guiding catheter thrombosis in either group. There was a higher incidence of periprocedural MI in the heparin arm compared with the control arm (3.1% vs. 1.7%, p < 0.05).

Efficacy: Time of manual compression was longer in the heparin group (13.1 minutes vs. 5.4 minutes, p < 0.05). The authors used a number of different definitions for bleeding, including TIMI, GUSTO, STEEPLE, and ACUITY. In all instances, bleeding was lower in the control arm compared with the heparin arm. For example, the incidence of TIMI major bleeding was 0% in both arms, whereas the incidence of TIMI minor bleeding was 4.0% vs. 2.0% in the heparin and control arms, respectively.

Interpretation:

Among patients with stable angina undergoing elective PCI for non-complicated lesions, PCI without intravenous heparin is not associated with increased complications or adverse events compared to PCI with heparin. However, it should be noted that this was a small, single-center trial conducted in very low-risk patients.

Heparin was not administered systemically in the placebo group, but could be used to flush the catheters. The lack of catheter thrombosis without an anticoagulant in the present study differs from the risk of catheter thrombosis without adequate anticoagulation seen in acute coronary syndrome patients, such as was observed in the OASIS trial. The duration of the procedure in the present study (mean 11 minutes) was extremely short and reflects the very low risk of the patients in the trial. These data, while provocative, should be verified in a larger, multicenter, randomized trial before this technique can be considered as an alternative in patients undergoing PCI.

References:

Stabile E, Nammas W, Salemme L, et al. The CIAO (Coronary Interventions Antiplatelet-based Only) Study: A randomized study comparing standard anticoagulation regimen to absence of anticoagulation for elective percutaneous coronary intervention. J Am Coll Cardiol 2008;52:1293-8.

Presented by Dr. Eugenio Stabile at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2006), Washington, DC, October 2006.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Anticoagulation Management and ACS, Interventions and ACS, Chronic Angina

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Angina, Stable, Thrombosis, Heparin, Constriction, Pathologic, Diabetes Mellitus, Stents, Percutaneous Coronary Intervention


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