Third Randomized Intervention Treatment of Angina - RITA-3
This was a randomized trial comparing an early invasive approach with a selective invasive approach in patients with unstable angina/non–ST-segment elevation myocardial infarction (NSTEMI).
Contribution to the Literature: The RITA-3 trial showed that invasive therapy was associated with a reduction in early death, MI, or refractory angina at 4 months.
Patients Enrolled: 1,810 (895 intervention) (915 conservative)
Mean Follow Up: 1, 5, and 10 years
Mean Patient Age: 63 years
- First co-primary endpoint was death, nonfatal MI, or refractory angina at 4 months
- Second co-primary endpoint was death or nonfatal MI at 1 year
Patients with unstable angina/NSTEMI were randomized to early invasive therapy (n = 895) versus selective invasive therapy (n = 915).
Aspirin (92%), enoxaparin (84%), any heparin (94%), angiotensin-converting enzyme inhibitor (17-19%), HMG-CoA reductase inhibitor (45%), clopidogrel (91% of patients treated with percutaneous coronary intervention [PCI]), glycoprotein IIb/IIIa receptor antagonist (24% of patients treated with PCI). Upon discharge, >70% of patients were treated with beta-blockers and lipid-lowering agents, and >90% were treated with aspirin.
At 4 months, the combined endpoint occurred in 9.6% of patients treated with the early invasive strategy compared to 14.5% of those treated conservatively (p = 0.0001; relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85). Similarly, the rate of the combined endpoint at 1 year was lower in the invasive arm (13.5% vs. 18.4%; p = 0.003; RR, 0.72; 95% CI, 0.58-0.90). At both time periods, the rates of death or MI were not significantly different and the composite endpoint was primarily due to a difference in refractory angina. At 12 months, the incidence of refractory angina was 6.5% in the invasive group and 11.6% in the conservative group (p < 0.001; RR, 0.56; 95% CI, 0.41-0.76).
The RITA-3 trial used the prespecified definition of MI to be: 1) clinical syndrome + development of Q waves, or 2) ST-segment elevation + enzymes or marker 2x upper limit of normal. If patients in RITA-3 were analyzed using the European Society of Cardiology (ESC)/American College of Cardiology (ACC) definition of MI, a significant difference in the rate of MI was noted at 4 months (8.9% invasive vs. 13.0% conservative; p = 0.006) and 12 months (9.4% invasive vs. 14.1% conservative; p = 0.002). In patients randomized to the invasive arm, 97% underwent angiography within a median time of 2 days. PCI was performed in 36% at a median time of 3 days. Coronary artery bypass grafting was performed in 21% with a 30-day mortality of 3%.
At 5 years, revascularization had occurred in 61% of the early invasive group vs. 38% of the selective invasive group.
All-cause mortality at 10 years was 25.1% vs. 25.4% (p = 0.94), respectively, for the early vs. selective invasive group. This observation was seen among high-, intermediate-, and low-risk individuals. Independent predictors of mortality included: age, previous MI, heart failure, smoking, diabetes, heart rate, and ST-segment depression.
Cardiovascular mortality at 10 years was 15.1% vs. 16.1% (p = 0.65), respectively.
The major benefit of an early invasive strategy in this trial was in the prevention of refractory angina. When the current ESC/ACC guidelines for the definition of MI are applied, RITA-3 showed that an early invasive strategy was also effective in reducing MI due to small enzyme elevations. The overall rates of revascularization were low, with only 61% undergoing revascularization in the early invasive arm.
Early invasive therapy was associated with a reduction in cardiovascular and all-cause mortality at 5 years; however, this benefit was lost by 10 years. This trial enrolled participants from 1997 to 2001; therefore, background medical therapy does not reflect current practice. For example, at baseline, only 45% of participants were on statin therapy. In addition to less than optimal medical therapy, the late mortality catch-up in the early invasive group may reflect outdated revascularization procedures. For example, patients were revascularized by angioplasty and bare-metal stents, which may have resulted in restenosis and acute coronary syndromes in a significant proportion of patients.
Henderson RA, Jarvis C, Clayton T, Pocock SJ, Fox KA. 10-Year Mortality Outcome of a Routine Invasive Strategy Versus a Selective Invasive Strategy in Non–ST-Segment Elevation Acute Coronary Syndrome: The British Heart Foundation RITA-3 Randomized Trial. J Am Coll Cardiol 2015;66:511-20.
Editorial: Patel MR, Ohman M. The Early Invasive Strategy in Acute Coronary Syndromes: Should the Guideline Recommendations Be Revisited? J Am Coll Cardiol 2015;66:521-3.
Presented by Dr. Robert Henderson at the European Society of Cardiology Congress, Barcelona, Spain, September 2, 2014.
Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet 2002;360:743-51.
Presented by K.A. Fox at the European Society of Cardiology Congress, August 31, 2002.
Keywords: Risk, Myocardial Infarction, Acute Coronary Syndrome, Coronary Disease, Confidence Intervals, Coronary Artery Bypass, Angioplasty, Stents, ESC Congress
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