Invasive Strategy in Women With Non–ST-Elevation Acute Coronary Syndromes - Invasive Strategy in Women With NSTE ACS

Feb 13, 2009
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Trial Sponsor:
Sanofi-Aventis, Organon, and GlaxoSmithKline
Date Presented:
01/01/2007
Date Published:
01/01/2009
Date Updated:
02/13/2009
Original Posted Date:
02/13/2009
References

Description:

The goal of the trial was to evaluate a strategy of routine early coronary angiography with a selective invasive strategy among women with non–ST-elevation (NSTE) acute coronary syndromes (ACS) also enrolled in the OASIS-5 trial.

Hypothesis:

Among women with an ACS, a routine invasive strategy would be superior.

Study Design

Study Design:

Patients Enrolled: 184
Mean Follow Up: 2 years
Mean Patient Age: Mean age, 68 years
Female: 100

Patient Populations:

Women with two of the following three criteria:
  • Age >60 years
  • Elevated troponin or creatinine kinase-MB isoenzyme
  • Ischemic electrocardiographic changes

Exclusions:

  • Unable to take low-molecular weight heparin
  • Prior hemorrhagic stroke
  • Pre-existing indication for anticoagulation other than ACS
  • Age <21 years
  • Pregnancy
  • Life expectancy <6 months
  • Renal insufficiency

Primary Endpoints:

  • Death, MI, or stroke at 2 years

Secondary Endpoints:

  • Individual components of the primary outcome
  • Major bleeding

Drug/Procedures Used:

A subset of female patients in the OASIS-5 trial (n = 184) were randomized to a strategy of routine early coronary angiography (n = 92) performed within 7 days with intervention as needed, or a selective invasive strategy (n = 92) with coronary angiography performed only in case of symptoms or positive stress testing.

Concomitant Medications:

There were no medication differences between the groups during the initial hospitalization. Among the routine invasive group, the use of aspirin was 100%, thienopyridine was 86%, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was 71%, beta-blocker was 95%, and lipid-lowering drug was 88%.

Principal Findings:

Overall, 184 women were enrolled in the trial. At study entry, 22% of patients had a prior myocardial infarction (MI) and 25% had diabetes. The mean time from symptom onset to randomization was 11 hours in the routine invasive group and 13 hours in the selective invasive group. The majority of patients were biomarker positive (79%), while 47% had at least 1 mm of ST-depression. In-hospital coronary angiography was performed in 95.7% of the routine invasive group and 40.2% of the selective invasive group. Likewise, percutaneous coronary intervention (PCI) was performed more frequently in the routine invasive group (45.7%) compared with the selective invasive group (23.9%), as was coronary artery bypass grafting (CABG) (12.0% vs. 6.5%). Through long-term follow-up, the difference in PCI narrowed to 48.0% of the routine invasive group and 39.0% of the selective invasive group, and the difference in CABG narrowed to 16% vs. 12%, respectively.

There was no difference in the primary endpoint of death, MI, or stroke at 2 years between the routine and selective invasive group (21.0% vs. 15.4%, hazard ratio [HR] 1.46, p = NS). There was also no difference in the composite of death, MI, or recurrent ischemia (21.0% vs. 20.8%) or death or MI (18.8% vs. 14.3%). Death trended higher in the routine invasive group (8.8% vs. 2.2%, HR 4.65, 95% confidence interval [CI] 0.97-22.2). Major bleeding occurred more frequently in the routine invasive group (10.0% vs. 2.2%, HR 6.90, 95% CI 1.48-32.1).

Interpretation:

Among women with NSTE ACS enrolled in the OASIS-5 trial, use of a routine invasive strategy was not associated with improvements in the composite endpoint of death, MI, or stroke through 2 years compared with a selective invasive strategy.

While there was no difference in the primary composite endpoint, major bleeding was more frequent in the routine invasive strategy group and mortality trended higher. It should be noted that the sample size of the present study was quite small (n = 184). Larger trials of an invasive strategy have shown mixed results in women, with some such as TACTICS-TIMI 18 showing a similar treatment benefit of death and MI and others such as RITA 3 and FRISC 2 showing a possible hazard with a routine invasive strategy. During the follow-up phase, the rate of PCI between the two groups narrowed from ~20% difference to a <10% difference. A meta-analysis (four trials with men and five trials with women) included in the present manuscript documents a 30% reduction in mortality among men and a 51% increase in mortality among women undergoing routine invasive therapy.

References:

Swahn E, Alfredsson J, Afzal R, et al. Early invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes: a substudy of the OASIS 5 trial and a meta-analysis of previous randomized trials. Eur Heart J 2009;Feb 7:[Epub ahead of print].

Presented by Dr. Eva Swahn at the European Society of Cardiology Congress, September 2007, Vienna, Austria.

Keywords: Stroke, Isoenzymes, Myocardial Infarction, Follow-Up Studies, Creatinine, Percutaneous Coronary Intervention, Biomarkers, Coronary Angiography, Myocardial Revascularization, Confidence Intervals, Coronary Artery Bypass, Diabetes Mellitus, Troponin


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