Author + information
- Received February 10, 2010
- Revision received March 4, 2010
- Accepted March 11, 2010
- Published online June 1, 2010.
- Keith A.A. Fox, BSc, MB, ChB⁎,⁎ (, )
- Tim C. Clayton, BSc, MSc†,
- Peter Damman, MD‡,
- Stuart J. Pocock, BSc, MSc, PhD†,
- Robbert J. de Winter, MD, PhD‡,
- Jan G.P. Tijssen, PhD‡,
- Bo Lagerqvist, MD, PhD§,
- Lars Wallentin, MD, PhD§,
- FIR Collaboration
- ↵⁎Reprint requests and correspondence:
Prof. Keith A. A. Fox, Centre for Cardiovascular Science, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom
Objectives This study was designed to determine: 1) whether a routine invasive (RI) strategy reduces the long-term frequency of cardiovascular death or nonfatal myocardial infarction (MI) using a meta-analysis of individual patient data from all randomized studies with 5-year outcomes; and 2) whether the results are influenced by baseline risk.
Background Pooled analyses of randomized trials show early benefit of routine intervention, but long-term results are inconsistent. The differences may reflect differing trial design, adjunctive therapies, and/or limited power. This meta-analysis (n = 5,467 patients) is designed to determine whether outcomes are improved despite trial differences.
Methods Individual patient data, with 5-year outcomes, were obtained from FRISC-II (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Trial of a Conservative Treatment Strategy Versus an Interventional Treatment Strategy in Patients with Unstable Angina) trials for a collaborative meta-analysis. A Cox regression analysis was used for a multivariable risk model, and a simplified integer model was derived.
Results Over 5 years, 14.7% (389 of 2,721) of patients randomized to an RI strategy experienced cardiovascular death or nonfatal MI versus 17.9% (475 of 2,746) in the selective invasive (SI) strategy (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.71 to 0.93; p = 0.002). The most marked treatment effect was on MI (10.0% RI strategy vs. 12.9% SI strategy), and there were consistent trends for cardiovascular deaths (HR: 0.83, 95% CI: 0.68 to 1.01; p = 0.068) and all deaths (HR: 0.90, 95% CI: 0.77 to 1.05). There were 2.0% to 3.8% absolute reductions in cardiovascular death or MI in the low- and intermediate-risk groups and an 11.1% absolute risk reduction in highest-risk patients.
Conclusions An RI strategy reduces long-term rates of cardiovascular death or MI and the largest absolute effect in seen in higher-risk patients.
The collaboration and the meta-analysis were conducted using resources from the host institutions for the respective studies (Dr. Fox is supported by the British Heart Foundation; Dr. Wallentin is supported by the Swedish Heart Foundation) and from the London School of Hygiene and Tropical Medicine. The original studies were supported as stated in the original reports. Dr. Fox has received grants and honoraria from Sanofi-Aventis/Bristol-Myers Squibb, GlaxoSmithKline, Lilly, and AstraZeneca. Dr. Pocock has consulted for The Medicines Company, and has served on a Boston Scientific-sponsored Data Monitoring Committee.
- Received February 10, 2010.
- Revision received March 4, 2010.
- Accepted March 11, 2010.
- American College of Cardiology Foundation