New Meta-Analysis: Routine Invasive Strategy Betters Selective Care for Non-ST-Elevation ACS

March 14, 2010

March 14, 2010 (Atlanta, Georgia) A new meta-analysis of all relevant studies comparing a more aggressive routine invasive strategy with a more conservative selective invasive strategy in patients with non-ST-elevation acute coronary syndrome has clearly shown that the more aggressive treatment approach leads to better long-term outcomes.

Dr Keith AA Fox


Dr Keith AA Fox (University of Edinburgh, Scotland) presented the findings here at the American College of Cardiology (ACC) 2010 Scientific Sessions today. "The key result is that five years after the randomization, there is a net absolute difference of 3.2% and a 19% relative risk reduction in cardiovascular death and MI in the routine invasive group, and I don't know of any pharmacological therapy that has that five years from randomization," Fox told heartwire .

The analysis, known as the FIR trial collaboration, included the FRISC II, ICTUS, and RITA-3 trials, and Fox said it was performed because "there was ambiguity about the long-term findings of the individual studies. It is only with this combined analysis that we can get a conclusive result. The study has demonstrated that there is a clear impact on reduced cardiovascular death and heart attack."

The current ACC/AHA guidelines state that, unless a person has especially high-risk features, either a conservative or an aggressive strategy is appropriate, Fox noted. "What this says is that we have to relook at that, because they are not equal. This is pooling all of the data from all of the trials based on individual patient data with five-year outcomes, and it shows a robust benefit overall. I think the guidelines will be updated in light of all the available evidence."

Highest-Risk Patients Benefited Most

Fox, who was also the lead investigator of RITA-3, explained that a routine invasive strategy is early angiography with subsequent PCI or CABG surgery, whereas a selective invasive strategy means angiography that is performed only if refractory angina or rest ischemia occurs despite optimal medical therapy.

The combined analysis of the three trials consisted of 2721 patients who were randomized to the routine invasive strategy and 2746 patients who received the more conservative selective invasive strategy.

The most marked treatment effect was seen for nonfatal MI alone, which occurred in 10% of the routine invasive cohort, compared with 12.9% of the selective invasive cohort, but the researchers also saw a lower number of CV deaths in the routine cohort.

Primary Outcomes of Combined Data Set at Five Years

Outcomes Selective invasive, % (n=2746) Routine invasive, % (n=2721) Hazard ratio p
MI 12.9 10.0 0.77 0.001
CV death 8.1 6.8 0.83 0.068
CV death/MI 17.9 14.7 0.81 0.002
All-cause mortality 11.7 10.6 0.90 0.190
All-cause mortality/MI 20.9 18.1 0.85 0.008

In addition, Fox and colleagues found that patients in the highest-risk group benefited the most from undergoing the routine invasive strategy.

Although the high-risk patients are more difficult and more challenging, they stand to profit most.

Paradoxically, these patients are usually less likely to receive interventions, he said, explaining that there is evidence from registries that "low-risk people are more likely to be treated aggressively than high-risk people--because, as cardiologists, we are risk-averse. If we think somebody has got increased hazard, we are more likely to stand back. This says think again, there's more to gain than risk. Although the high-risk patients are more difficult and more challenging, they stand to profit most."

Treatment Effect by Integer Risk Category, CV Death, or MI

Risk category Low Mid High
Risk score 0-4 5-8 >9
Selective invasive, % 10.2 21.1 44.1
Routine invasive, % 8.2 17.3 33.0
Hazard ratio 0.80 0.81 0.68
Absolute risk difference -2.0 -3.8 -11.1

Call for Systematic Risk Stratification; Use the GRACE Score

The findings lend support to the idea of systematically risk-stratifying patients using a simple tool, such as the GRACE or TIMI risk score, to determine who should receive an intervention, he said. "If patients are high risk and without contraindication but they are not going for an invasive strategy, we need to ask why. My recommendation is that patients should be risk-stratified, because clearly there is a most potent benefit in the highest-risk group," Fox told heartwire .

Risk stratification is crucial, he said, because although the moderate- to low-risk patients also benefit, "if you just do what we are doing now, people are bypassing the high-risk group. People get stratified now on the basis of troponin, and although troponin is one of the risk markers, it's only one. If you perform more reliable risk stratification, you can identify high-risk people. The most robust algorithm that is recommended as number one by the European Society of Cardiology guidelines and one of the ones recommended by the ACC/AHA guideline is the GRACE score, because it's been validated in independent populations."

But Fox explained that the GRACE score was not actually used in this meta-analysis because not all of the studies had collected all of the parameters--age, heart rate, systolic BP, creatinine, heart-failure Killip class, cardiac arrest on admission, ST-segment deviation, and elevated cardiac enzymes/markers; rather, a "shorthand" nomogram was employed by the physician at the bedside.

But "it's not as robust as the GRACE score, and we are encouraging doctors to use the GRACE score. In fact, it doesn't even need a doctor; in our institution, whichever healthcare professional is the first to triage the patient does it on their palmtop, phone, or laptop, and it takes about 30 seconds." A high GRACE score is "a trigger for immediate catheterization and more aggressive pharmacologic therapy," he explained.

Fox said studies have shown that up to two elements from the GRACE score can be missed; for example, hospital staff might not know creatinine or Killip class in the emergency department, and it still performs well.


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