A Long-Term Perspective on the Protective Effects of an Early Invasive Strategy in Unstable Coronary Artery Disease: 15-Year Follow-Up of the FRISC-II Invasive Study - FRISC-II


The goal of this study was to evaluate treatment with an early invasive strategy compared with a conservative management strategy on late clinical events.

Contribution to the Literature: The FRISC-II trial showed that early invasive therapy reduced the incidence of death or myocardial infarction (MI) in non-ST-elevation acute coronary syndrome.

Study Design

Patients Enrolled: 2,457
Mean Follow-Up: 2, 5, and 15 years

Patient Populations:

Patients from three Scandinavian countries with ischemic symptoms in previous 48 hours accompanied by ECG changes (ST depression or T-wave inversion ≥0.1 mv) or elevated markers (e.g., creatine kinase-MB >6 mg/L, troponin T >0.10 mg/L)


Increased bleeding risk, anemia, thrombolytic indication in past 24 hours, percutaneous coronary intervention in previous 6 months, scheduled angiography/revascularization, other acute/severe cardiac disease, renal or hepatic insufficiency, or known clinically relevant osteoporosis. Those with previous open heart surgery and age >75 years were not eligible for invasive strategy assignment, but were assigned to dalteparin or placebo.

Primary Endpoints:

Composite of death or MI

Drug/Procedures Used:

Fast Revascularization during InStability in Coronary artery disease (FRISC-II) was a prospective randomized trial and compared an early invasive with a conservative management strategy in patients with unstable coronary artery disease. The early invasive strategy included angiography in all patients and, if needed, revascularization. The conservative strategy included initial medical management with exercise testing; if needed, angiography could be performed based on the results of the exercise testing.

The primary endpoint was a composite endpoint of death or MI at 6 months. The invasive versus conservative comparison was carried out in a factorial design. Half of the patients within each group were also randomized to continued treatment with subcutaneous dalteparin or placebo for 3 months.

Principal Findings:

At 2-year follow-up, lower rates of death (n = 45 [3.7%] vs. 67 [5.4%]; risk ratio [RR] 0.68 [95% confidence interval (CI) 0.47-0.98]; p = 0.038), MI (n = 111 [9.2%] vs. 156 [12.7%]; RR 0.72 [95% CI 0.57-0.91]; p = 0.005), and the composite endpoint of death or MI (n = 146 [12.1%] vs. 200 [16.3%]; RR 0.74 [95% CI 0.61-0.90]; p = 0.003) were observed in the invasive compared with the conservative management group. During the second year, 18 patients died in the invasive group and 19 in the conservative management group (p = NS).

At 5-year follow-up, revascularization had been performed in 80% of the invasive group and 52% of the conservative group. Mortality did not differ between treatment groups (9.7% for invasive strategy vs. 10.1% for conservative strategy, p = 0.69), but the composite of death or MI was lower in the invasive strategy (19.9% vs. 24.5%, p = 0.009), driven by a reduction in MI (12.9% vs. 17.7%, p = 0.002). There was also no difference in cardiac death (5.6% vs. 5.9%, p = 0.77). The reduction in death or MI was restricted to higher risk patients, with no benefit in patients with a FRISC risk score of 0-1 (death or MI 10.3% for invasive strategy vs. 8.2% for conservative strategy, RR 1.26).

At 15-year follow-up, death or MI had occurred in 75.9% of the early invasive group versus 84.2% of the conservative therapy group (p = 0.002).


Among patients with unstable angina, an early invasive approach was associated with a reduction in mortality at 2 years compared with a conservative management strategy, but these findings were not maintained through 5 years, when there was no difference in death between treatment strategies.

Reductions in the composite of death or MI were limited to higher risk patients, with a nonsignificantly higher risk of death or MI observed in low-risk patients.


Presented by Dr. Lars Wallentin at the European Society of Cardiology Congress, Rome, Italy, August 29, 2016.

Wallentin L, Lindhagen L, Ärnström E, et al., on behalf of the FRISC-II Study Group. Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study. Lancet 2016;Aug 29:[Epub ahead of print].

Editorial Comment: Weintraub WS. Invasive management of acute coronary syndromes. Lancet 2016;Aug 29:[Epub ahead of print].

Lagerqvist B, Husted S, Kontny F, et al., and the FRISC-II Investigators. A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: two-year follow-up of the FRISC-II invasive study. J Am Coll Cardiol 2002;40:1902-14.

5-year follow-up data presented by B. Lagerqvist, European Society of Cardiology Scientific Congress, September 2006.

Lagerqvist B, et al. 5-year outcomes in the FRISC-II randomised trial of an invasive versus a non-invasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study. Lancet 2006; 368: 998–1004.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and ACS, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, Angina, Unstable, Angiography, Coronary Artery Disease, Creatine Kinase, Dalteparin, Electrocardiography, Exercise Test, Myocardial Infarction, Myocardial Revascularization, Troponin T, ESC Congress

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