FRISC-II at 15 Years

Summary and Comment |
August 29, 2016

FRISC-II at 15 Years

  1. Harlan M. Krumholz, MD, SM

The overall advantage of an early invasive strategy for non–ST-elevation ACS persisted during long-term follow-up, but not thanks to a survival benefit.

  1. Harlan M. Krumholz, MD, SM

In the randomized FRISC-II trial, patients from Sweden, Denmark, and Norway with non–ST-elevation acute coronary syndrome (NSTEACS) had lower risk for death or myocardial infarction (MI) with an early invasive strategy than a noninvasive strategy, even at 5 years (NEJM JW Gen Med Nov 15 2006 and Lancet 2006; 368:998). Other analyses suggested that the invasive strategy's benefit was limited to men and to patients with elevated troponin levels. Investigators now report 15-year follow-up data on the 2457 FRISC II participants (mean age, 66; 70% men); 99% had 15-year mortality data, and fewer (89%) had 15-year data on other endpoints, mostly because of administrative difficulties in Norway.

The early invasive strategy was associated with postponement of death or MI by a mean of 18 months, principally because that group had significantly fewer adverse events than the noninvasive group within 3 to 4 years after randomization. The mortality advantage, on its own, did not persist through long-term follow-up. The invasive strategy's overall benefit did not extend to patients without troponin T elevation; patients with lower levels of growth differentiation factor-15, a marker of inflammation; or women (although the female sample size was fairly small).


Since 1999, when FRISC-II was first published, much has changed in how NSTEACS is managed, mostly related to systems of care. Nevertheless, this long-term follow-up is welcome: It reaffirms FRISC-II's initial finding of an overall benefit from the early invasive approach, reveals that the benefit does not extend specifically to long-term survival, and more precisely identifies which subgroups derive the overall benefit. The findings highlight the ongoing need for research on how to optimize the pursuit, timing, and types of procedures for this population.

Editor Disclosures at Time of Publication

  • Disclosures for Harlan M. Krumholz, MD, SM at time of publication Consultant / Advisory board United Healthcare (Advisory Board); Element Science (Consultant) Equity ImageCor; Hugo PHR Grant / Research support Agency for Healthcare Research and Quality; Food and Drug Administration; National Heart, Lung, and Blood Institute; Robert Wood Johnson Foundation; Medtronic; Johnson & Johnson; Chinese National Center for Cardiovascular Disease; Centers for Medicare & Medicaid Services Editorial boards; American Journal of Managed Care; American Journal of Medicine; Archives of Medical Science; Critical Pathways in Cardiology; Current Cardiovascular Risk Reports; JACC: Cardiovascular Imaging; Circulation: Cardiovascular Quality and Outcomes; Circulation (Associate Editor)


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