Elsevier

The Lancet

Volume 356, Issue 9223, 1 July 2000, Pages 9-16
The Lancet

Articles
Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial

https://doi.org/10.1016/S0140-6736(00)02427-2Get rights and content

Summary

Background

The Fragmin and Fast Revascularisation during Instability in Coronary artery disease II trial (FRISC II) compared an early invasive with an early non-invasive strategy in unstable coronary-artery disease. We report outcome at 1 year.

Methods

2457 patients were randomly assigned invasive or non-invasive treatment and 3 months of dalteparin or placebo. Complete information at 1 year was available for 1222 in the invasive group and 1234 in the non-invasive group. Analyses were by intention to treat.

Findings

Revascularisation was done within the first 10 days in 71% of the invasive group and 9% of the non-invasive group and within the first year in 78% and 43%. During the first year, 27 (2·2%) patients in the invasive group and 48 (3·9%) in the non-invasive group died (risk ratio 0·57 [95% Cl 0·36–0·90], p=0·016). 105 (8·6%) versus 143 (11·6%) had myocardial infarction (0·74 [0·59–0·94], p=0·015). The composite of death or myocardial infarction occurred in 127 (10·4%) versus 174 (14·1%) patients (0·74 [0·60–0·92], p=0·005). There were also reductions in readmission (451 [37%] vs 704 [57%]; 0·67 [0·62–0·72]), and revascularisation after the initial admission (92 [7·5%] vs 383 [31%]; 0·24 [0·20–0·30]). The results did not interact with the dalteparin/placebo allocation.

Interpretation

After 1 year in 100 patients, an invasive strategy saves 1·7 lives, prevents 2·0 non-fatal myocardial infarctions and 20 readmissions, and provides earlier and better symptom relief at the cost of 15 more patients with coronary-artery bypass grafting and 21 more with percutaneous transluminal angioplasty. Therefore, an invasive approach should be the preferred strategy in patients with unstable coronary-artery disease and signs of ischaemia on electrocardiography or raised levels of biochemical markers of myocardial damage.

Introduction

Invasive procedures have become increasingly common early after an episode of unstable coronary-artery disease, even in patients who are clinically stabilised.1 The 6-month results of the FRISC II (Fast Revascularisation during Instability in Coronary artery disease) invasive trial2 showed a reduction in the composite endpoint of death or myocardial infarction with an invasive strategy in patients with unstable coronary-artery disease and signs of ischaemia as shown by electrocardiography (ECG) or rises in biochemical markers of myocardial damage. These results provoked much debate because two previous large-scale randomised trials had not shown similar results.3, 4 The FRISC II medical trial showed that, within the non-invasive strategy group, extended treatment with dalteparin for 3 months significantly lowered the risk of death, myocardial infarction, and need for revascularisation; thus, this approach might be an alternative strategy.5 The endpoint of myocardial infarction could be invalid because detection, definition, and impact of myocardial infarction differ according to whether it occurs during revascularisation procedures (as in most events in the group treated by the invasive strategy) or spontaneously (as in most events in the group treated non-invasively). Thus, further documentation was needed of the results of the invasive versus non-invasive comparison in the FRISC II trial for mortality only, long-term risk of myocardial infarction, and the long-term outcome among patients treated with dalteparin or placebo. The outcome of the continued follow-up will influence whether the FRISC II invasive trial changes the current treatment guidelines for unstable coronary-artery disease, which will have important consequences for management of patients and for treatment costs. We report here the 1-year results of the randomised invasive versus non-invasive strategy in terms of death, myocardial infarction, and the need for readmission and revascularisation procedures and the outcome in the long-term dalteparin versus placebo cohorts and in predefined subgroups based on commonly used risk indicators.

Section snippets

Patients

Patients were eligible for inclusion if they had symptoms of ischaemia that were increasing or occurring at rest or raised the suspicion of acute myocardial infarction, with the last episode preceding the first dose of dalteparin or standard heparin by less than 48 h. Furthermore, myocardial ischaemia had to be verified by ECG (ST-segment depression ≥0·1 mV or T-wave inversion ≥0·1 mV), or by raised biochemical markers (creatine kinase MB isoenzyme >6 μg/L, troponin T ≥0·10 μg/L, qualitative

Characteristics of patients and procedures done

2457 patients were randomly assigned the invasive or the non-invasive regimen and 3 months' treatment with dalteparin or placebo. In January, 2000, complete information on vital status was available from 2456 patients with a last contact at least 335 days after randomisation. We lacked information on vital status and myocardial infarction at 12 months for one patient from the non-invasive group and information on myocardial infarction for three patients in the invasive group because of

Discussion

The most important new finding in this 1-year follow-up of the invasive versus non-invasive comparison in the FRISC II trial is the significant and clinically relevant absolute and relative reductions in 1-year mortality when an invasive strategy is adopted. Furthermore, the survival analysis indicates a continuously increasing separation of the event rates. The 1-year follow-up documents a treatment alternative—the invasive strategy—that is able to reduce long-term mortality in unstable

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