RITA-3: Advantage of Routine Invasive Strategy for NSTE-ACS Gone by 10 Years

BARCELONA, Spain—After 10 years, the mortality benefit observed at 5 years with routine invasive treatment of non-ST segment acute coronary syndromes (NSTE-ACS) is no longer apparent. Findings from the RITA-3 randomized trial were presented September 2, 2014, at the European Society of Cardiology Congress.

Given the long follow-up duration, however, the RITA-3 results may not reflect what is possible with contemporary intervention strategies, reported Robert A. Henderson, MD, of Nottingham University Hospitals (Nottingham, England).


Between 1997 and 2001, RITA-3 researchers randomized 1,810 patients with NSTE-ACS to undergo 1 of 2 treatment strategies:

  • Routine invasive (n = 895): angiography within 72 hours followed by medical therapy or revascularization (PCI/CABG) as indicated
  • Selective invasive (n = 915): medical management and, in patients showing signs of ischemia, angiography with or without revascularization (PCI/CABG) as needed
In previously presented 5-year results, the routine invasive strategy was associated with a 26% reduction in CV death and MI as well as a 24% reduction in all-cause mortality. The greatest benefits were derived from patients at highest baseline ischemic risk. In all, 61% of those in the routine invasive arm and 38% of the selective invasive arm underwent revascularization.
The current analysis assessed the prespecified secondary outcome of all-cause mortality at 10 years.

Treatment Strategy, Time Interact with Long-Term Mortality

All-cause and CV mortality were similar for the 2 groups at 10 years. There was an interaction between treatment strategy and time (P = .006 for interaction), such that a greater proportion of the deaths happened from 5 to 10 years (vs before 5 years) in the routine invasive group compared with the selective invasive groups (table 1).

Table 1. Mortality in NSTE-ACS Patients by Strategy





Log-rank P Value

Death at 10 Years

    Before 5 Years

    5-10 Years








CV Death at 10 Years




On multivariable analysis, several baseline characteristics independently predicted 10-year all-cause mortality (table 2).

Table 2. Independent Predictors of 10-Year Mortality


Adjusted OR (95% CI)

P Value

Age, per 10 years

4.43 (3.63-5.41)

< .001


   Previous vs None

    Current vs None


1.56 (1.11-2.18)

2.89 (1.99-4.20)


< .001


2.27 (1.64-3.14)

< .001

Previous MI

1.75 (1.34-2.28)

< .001


1.64 (1.28-2.10)

< .001

Heart Failure

1.93 (1.22-3.06)


Male vs Female Sex

1.30 (1.00-1.68)



Long-term mortality risk coincided with post-discharge GRACE risk, which the RITA-3 researchers divided into 3 categories.

“For the low-risk group and medium-risk group, there is really no evidence of a difference between the 2 treatment strategies. For the high-risk group, there was some divergence of the curves for all-cause mortality out to 5 years, with an absolute difference in all-cause mortality at 5 years of 11.4%, but thereafter the difference in mortality between the 2 treatment arms attenuated,” Dr. Henderson explained. “At 10 years, there was no overall mortality in the high-risk group, and most importantly, there was no risk-treatment interaction, with a P value of .79).” 

Dr. Henderson reported that a meta-analysis using individual patient data from 3 trials investigating the value of routine invasive treatment—FRISC II, ICTUS, and RITA-3—is planned. “Further trials of contemporary intervention strategies in patients with NSTE-ACS are warranted, perhaps particularly in high-risk patients,” he concluded.

Long Time Horizon Presents Challenges

“How to comment in 3 minutes on what must be around 20 years of hard work?” said discussant Robbert J. de Winter, MD, PhD, of the University of Amsterdam (Amsterdam, The Netherlands).

Yet, he noted, the RITA-3 results must be contextualized. “It’s important to realize that for the patients to be included, the participating cardiologist had to be uncertain about the optimal medical strategy and continued medical therapy had to be an acceptable treatment option,” he said. “So basically, these patients were stabilized, angina-free, and hemodynamically stable. There were no arrhythmias and no overt heart failure.” 

The 3 aforementioned trials all showed different long-term patterns, he continued. At 2 years, FRISC II demonstrated a mortality benefit from routine invasive treatment, whereas RITA-3 and ICTUS did not. At 5 years, RITA-3 showed a benefit but FRISC II did ICTUS did not. At 10 years, the advantage for routine invasive treatment in RITA-3 had disappeared. 

Dr. de Winter attributed these differences to chance, noting that forthcoming 10-year data from FRISC II and ICTUS may offer clarity. However, a limitation of these studies and RITA-3, he added, is that much has changed since their time of enrollment.

Still, Dr. de Winter agreed that conservative treatment is a reasonable strategy for lower-risk patients.


Henderson RA. 10-year mortality outcome of a routine invasive strategy in non-ST segment elevation acute coronary syndrome: the British Heart Foundation RITA-3 randomised trial. Presented at: European Society of Cardiology Congress; September 2, 2014; Barcelona, Spain.

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  • Dr. Henderson reports no relevant conflicts of interest.