Fast track — ArticlesInvasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study
Introduction
In unstable coronary-artery disease, early invasive procedures are common, despite lack of evidence for the superiority of this approach in randomised trials. No previous randomised trial1, 2, 3, 4 has shown any significant decrease in death and myocardial infarction in the invasively treated cohort. The VANQWISH trial3 showed raised mortality with an invasive approach early after non-Q-wave myocardial infarction. However, many observational studies and the randomised TIMI IIIb trial2, 4, 5 have shown shorter hospital stays, fewer readmissions, less ischaemia, and fewer symptoms with an early invasive approach. Because of this controversial information, the use and timing of revascularisation in unstable coronary-artery disease is variable, which might have important consequences for patients and costs of treatment.
The treatment of patients with unstable coronary artery disease has developed substantially since the first randomised trials were published. Anti-ischaemic treatment with β-blockade and nitrates and antithrombotic treatment with aspirin and heparin, preferably low-molecular-mass heparin, is currently recommended for all patients in the acute phase.6, 7, 8, 9, 10 The results of invasive procedures have been improved by the use of stenting and glycoprotein IIb/IIIa blockade during percutaneous coronary interventions11, 12, 13, 14 and by technical improvements in surgical procedures, anaesthesia, and postoperative care.15
We designed the Fast Revascularisation during InStability in Coronary artery disease (FRISC II) invasive trial to compare an early invasive with a non-invasive trategy in patients with unstable coronary-artery disease in addition to optimum background antithrombotic medication. Since the optimum duration of low-molecular-mass heparin treatment in unstable coronary-artery disease has yet to be determined, we used a factorial design.
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Patients
We recruited patients between June 17, 1996, and May 7, 1998, in 58 Scandinavian hospitals, 16 of which were interventional centres. Patients were eligible for inclusion if they had symptoms of ischaemia that were increasing or occurring at rest, or that warranted the suspicion of acute myocardial infarction, with the last episode within 48 h before the start of dalteparin or standard heparin treatment. Myocardial ischaemia had to be verified by electrocardiography (ST depression ≥0·1 mV or
Study design
The FRISC II, study was a prospective, randomised, multicentre trial with parallel groups. We compared invasive and non-invasive treatments by factorial design. Randomisation was done by telefax through an independent organisation (Clinical Data Care, Lund, Sweden). Half of the patients in each group were randomly assigned long-term treatment with subcutaneous dalteparin or placebo for 3 months. The comparison of the invasive and non-invasive strategies was open and the comparison of long-term
Endpoints
Our primary objective was to compare the effects of invasive and non-invasive strategy on the composite endpoint of death and Myocardial infarction after 6 months. Other predefined endpoints were total death, myocardial infarction, symptoms of angina, need for late coronary angiography and revascularisation, bleeding episodes, and stroke. The trial should also report effects of the two treatment strategies in predefined subgroups based on age, sex, hypertension, smoking, diabetes, previous
Statistical analysis
Our hypothesis was that there would be a 32% decrease from 11·0% to 7·5% in the primary composite endpoint of death or myocardial infarction at 6 months with the early invasive strategy compared with the non-invasive strategy. To show such a decrease, a sample size of 2400 was required to obtain 80% power to show a significant difference at 2α=0·05.
We did statistical analyses according to intention to treat. The primary efficacy analysis was based on events occurring from start of open-label
Results
2457 of 3048 eligible patients were randomly assigned treatment (figure 1). The reasons for exclusion of 591 patients were: previous open heart surgery (256), old age (282), and other reasons (53). Of those excluded for old age, the median age was 80·4 years.
The two groups did not differ significantly for baseline characteristics (table 1).
Details of coronary angiography are shown in table 2. Revascularisation procedures (table 3, figure 2) were done within the first 10 days in 71% and 9% and
Discussion
We showed a significant decrease in death and myocardial infarction with an early invasive treatment strategy in unstable coronary-artery disease. The population investigated was recruited in three countries and included primary, secondary, and tertiary hospitals, with and without invasive facilities. We succeeded in recruiting patients at intermediate to high risk, a substantial proportion of whom were elderly men with chest pain at rest and signs of continuing ischaemia, myocardial damage, or
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