Brisbane, Australia - Much more research is needed to determine whether an early invasive strategy or conservative medical management is the best approach for acute coronary syndromes, says the lead investigator of a new review [1].

Dr Michael R Hoenig (Brisbane, Australia) and colleagues publish their review of five contemporary studies conducted in the stent era July 19, 2006 in the Cochrane Database of Systematic Reviews. Although the analysis showed that an early invasive approach was superior to conservative management for the main composite end points, there was a price to pay in the form of increased procedural MI and bleeding.

Hoenig told heartwire: "Angiography and stenting are no panacea . . . [and] have a significant residual event rate. We need more contemporary trials on this topic—we are far from having as solid an answer as we need given the prevalence and costs associated with treating this disease."

The key is to stratify patients by risk, he adds, with the available data suggesting that those at especially high risk will benefit from an early invasive approach. At the current time, "the TIMI score is the best method for stratifying risk," he says, although the absolute level of risk at which intervention becomes warranted remains to be determined. There are other unanswered questions, he adds, which is why considerably more work is needed in this field.

Hoenig et al included five studies with 7818 participants in their analysis—TACTICS-TIMI 18, ICTUS, RITA-3, FRISC-II, and VINO—with the primary aim of determining the benefits and risks of early invasive strategy compared with conservative medical management. They also examined the risk/benefit ratio of an early invasive strategy with or without GP IIb/IIIa inhibitors vs a conservative approach.

"The most consistent and robust findings of this review are that an invasive strategy in UA/NSTEMI results in a significant 33% relative risk reduction for both the end points of refractory angina and rehospitalization at six to 12 months," the researchers say.

"While the invasive strategy is associated with a twofold increase in the risk of periprocedural MI, the available data suggest a significant 25% relative risk reduction for both the end points of death and MI assessed at two to five years. Hence, the early hazard associated with a routine invasive strategy must be weighted against potential long-term benefit in clinical end points."

In the current review, only two of the studies—TACTICS-TIMI-18 and ICTUS—involved routine use of GP IIb/IIIa inhibitors. "Without doubt," an invasive strategy is more likely to be beneficial if GP IIb/IIIa inhibitors are used routinely, Hoenig says.

But other questions remain, he adds, such as whether beginning GP IIb/IIIa inhibitors in the emergency room will further improve outcomes and whether newer agents such as prasugrel might make them redundant. "And what role will new antithrombotics such as fondaparinux or bivalirudin play?"

Another much-debated point is the optimum time to intervention in UA/NSTEMI, Hoenig explains. There was significant heterogeneity in the time to angiography for the early invasive strategy in the five studies included in the review—ranging from a mean of 6.2 hours in VINO to four days in FRISC II.

"As yet, we do not really know what the optimal time to intervention is. Some early studies suggested that a 'cooling off' period may be beneficial in reducing the hazard of intervention, and this is the reason for the FRISC-II investigators using a delayed invasive approach. However, the only randomized controlled trial to test an 'early invasive' vs a 'delayed invasive' approach showed that an early invasive approach is superior in reducing hard clinical end points," Hoenig says.

"Notably, this trial, ISAR-COOL, recruited high-risk patients and involved the routine use of GP IIb/IIIa inhibitors, while earlier studies suggesting that 'cooling off' may be beneficial did not incorporate GP IIb/IIIa inhibitors. Clearly, more trials are needed to answer this question, and the results of ISAR-COOL need to be confirmed."

The investigators found that the NSTEMI patients had most to gain from an early invasive approach because of their higher risk for recurrent events and postevent heart failure compared with UA patients. But Hoenig warns against using a positive troponin score alone to assess risk. "Troponin is a strong prognosticator and is incorporated into the TIMI score. While a positive troponin should never be overlooked, some troponin-negative patients may also be at high risk.

"Cleary, we do not want to catheterize every patient who walks in the door with chest pain," he continues. "The treating clinician needs to determine which patients are at high risk for recurrent events. The TIMI score has been validated in several trials. It incorporates information that is easily obtained from routine blood tests (eg, troponin) and the ECGs on admission as well as historical information. It provides a platform for easy communication of the risk for the patient between the emergency department physician and the cardiologist/internist who will be caring for the patient."

He adds that while "there is a plethora of novel factors that can be used to risk-stratify patients . . . that have received a large amount of media attention . . . they are generally not practical and may not influence management," particularly in those obviously at either low or high risk. Where these novel risk factors—such as BNP and CRP—may come into their own is in patients at intermediate risk, he believes.

Nevertheless, doctors need to ask themselves "if there is any point in using multiple markers to stratify risk to the nth degree, if we really cannot do anything above and beyond what we already have to treat our patients," he notes, stressing that that the simplest approach is often the most effective.

"To improve outcomes in patients with ACS, we need to get better at doing the simple (and often cheap) things first. The data from the CRUSADE registry are sobering.

"Clearly, as medical therapies for UA/NSTEMI improve, progressively less absolute benefit is to be gained by intervention, and hence the risk at which invasive intervention is warranted is likely to represent a moving target."