STOCKHOLM — A routine early invasive strategy in patients with non-ST-segment elevation acute coronary syndrome has been shown for the first time to reduce the long-term risks of death or nonfatal MI.
Five-year follow-up in the Randomized Intervention Trial of Unstable Angina (RITA-3) showed a significant 22% reduction in the relative risk of the combined end point of death or nonfatal MI and a 24% reduction in all-cause mortality with a strategy of early coronary angiography followed by revascularization, as compared with a conservative strategy of symptom-driven angiography, reported Keith A.A. Fox, M.B., at the annual congress of the European Society of Cardiology.
Other trials have shown that routine early intervention in patients with non-ST-segment elevation acute coronary syndrome (ACS) results in reduced ischemia, but they have not shown a significant mortality benefit. However, those studies involved follow-up of only 6–24 months' duration—not long enough for the early hazards of percutaneous intervention or coronary artery bypass surgery to be outweighed by the longer-term benefits of the resultant improved coronary perfusion.
RITA-3 has shown that the mortality curves do not differ much in the first year, but they progressively separate over time in favor of the early invasive strategy, said Dr. Fox, the Duke of Edinburgh Professor of Cardiology at the University of Edinburgh.
The trial was a British Heart Foundation-sponsored multicenter U.K. trial in which 1,810 patients with non-ST-elevation ACS were randomized to intervention within 72 hours or to a conservative management strategy.
The incidence of death or nonfatal MI at a median of 5 years of follow-up was 16.6% in the early intervention arm and 20.0% with conservative management. All-cause mortality was 12.1% with routine early intervention vs. 15.1% with a conservative strategy. There were 62 cardiovascular deaths in the early intervention arm and 90 in the comparison group.
A key finding at 5 years was that the benefits of an early invasive strategy were concentrated in patients with a high baseline risk of death or MI. Indeed, the benefits of the interventional strategy were statistically significant only for those in the upper half of risk.
“What is perhaps remarkable is that patients in the top eighth in terms of risk had a profound 56% reduction in the odds of death or MI with the early intervention strategy; those in the lowest quartile of risk had no evidence of benefit,” he said. “The clinical implications are that a strategy of routine angiography and intervention is appropriate for all moderate- and high-risk patients with non-ST-elevation ACS.”
This is consistent with current European Society of Cardiology and American College of Cardiology/American Heart Association guidelines for management of non-ST-elevation ACS, Dr. Fox noted.
Because the data analysis in RITA-3 was by intention to treat and a substantial number of patients in the conservative arm eventually underwent a revascularization procedure, the 5-year results probably underestimate considerably the true benefits of an early invasive strategy, he added.
Discussant Freek Verheugt, M.D., said an early invasive strategy is preferable because it reduces the risks of acute MI and rehospitalization.
An early invasive strategy didn't show a significant mortality benefit in a metaanalysis of seven clinical trials (JAMA 2005;293:2908–17), including the 1-year RITA-3 results. Nor did it reduce 1-year mortality, compared with a more conservative strategy in the recently published Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial involving 1,200 high-risk troponin T-positive Dutch patients (N. Engl. J. Med. 2005;353:1095–104) in which Dr. Verheugt was a coinvestigator. And in RITA-3, the P value for all-cause mortality at 5 years was 0.054—close but not quite statistically significant, noted Dr. Verheugt, professor and chairman of cardiology at University Medical Center, Nijmegen, the Netherlands.