Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 years follow-up of a prospective, randomised, multicentre study

Wallentin L, Lindhagen L, Ärnström E, et al.
Lancet 2016;388:1903–1911.

Background

The early invasive treatment (coronary angiography and, if appropriate, revascularization within 7 days) of non-STE-acute coronary syndrome (ACS) patients leads to significant reductions in death and recurrent myocardial infarction (MI) compared with non-invasive treatment, particularly in male patients with elevated troponin concentrations and elevated levels of the growth differentiation factor-15 (GDF-15) [1-3]. The sustained benefit of early invasive treatment in these patients is supported by 5 year follow-up data and the ESC guidelines recommend this therapeutic strategy [4,5].

The FRISC-II trial (1996-1998, n=2457) was the first study that showed this benefit of early invasive treatment after 5-years of follow-up. These analyses are now extended with a 15-17 year follow-up.
In this analysis, follow-up analysis of all CV outcomes in the total non-ST-ACS population and in subgroups was done. Moreover, data was related to the biomarkers troponin, NTproBNP, and anti-inflammatory marker GDF-15.

Main results

• Early invasive treatment was associated with a significant average postponement of death or next MI of approximately 18 months (95% CI: 6.8–29.6; P = 0.002). This postponement was mainly driven by a significantly lower rate of new events during the first 3–4 years after randomisation, with a similar risk of new events in the following years.
• Postponement of death or MI was longer in non-smokers and in patients with elevated troponin T. The largest benefit was observed in the subgroup of patients with GDF-15 concentrations >1800 ng/L, with an average postponement of death or next MI of 45 months (95% CI: 16.9–55.0; P interaction = 0.021).
• Total mortality during the first 3–4 years was different between the invasive and non-invasive groups, which was driven by a difference in cardiac mortality that tended to be similar during the whole follow-up period. These differences corresponded to 24 days average postponement of total death (95% CI: –99 to 147) and 53 days average postponement of cardiac death over the 15 years (95% CI: –45 to 150), and were not statistically significant.
• The rate of re-admissions for ischaemic heart disease was lower in the invasive group than in the non-invasive group during the initial 3–4 years and thereafter remained similar during follow-up. This resulted in a persistent benefit with the invasive treatment strategy, which was on average 37 months postponement of death or next re-admission for ischaemic heart disease (95% CI: 27.7–45.5, P < 0.0001). This benefit was similar across all subgroups.

Conclusion

In the 15 year follow-up of the FRISC-II trial, the early invasive compared with a non-invasive treatment strategy in patients with non-STE-ACS led to a sustained postponement of the occurrence of death or next MI by 18 months on average and of death and re-admission to hospital for ischaemic heart disease by 37 months. These findings strongly support early invasive treatment as the preferred strategy in most patients with non-STE-ACS, particularly those with elevated troponin-T and GDF-15 levels.

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References

1. Morrow DA, Cannon CP, Rifai N, et al. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA 2001;286: 2405–12.
2. Lagerqvist B, Safstrom K, Stahle E, et al; Investigators FISG. Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? FRISC II Study Group Investigators. J Am Coll Cardiol 2001;38: 41–48.
3. Wollert KC, Kempf T, Lagerqvist B, et al. Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome. Circulation 2007; 116: 1540–48.
4. Fox KA, Clayton TC, Damman P, et al. Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. J Am Coll Cardiol 2010; 55: 2435–45.
5. Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37: 267–315.