Holding off on coronary angiography for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and elevated cardiac troponin T is not associated with higher long-term risks of death or myocardial infarction (MI), a new report by Dutch researchers indicates.

The ICTUS trial compared a routine early invasive treatment strategy with an ischemia-driven strategy, both of which included anti-anginal and anti-thrombotic medical treatment. In the early invasive group, coronary angiography was done within 24 to 72 hours, followed by appropriate angiography-guided treatment, either revascularization or continued pharmacological therapy. In the ischemia-driven group, angiography was done only for refractory angina or when ischemia was inducible by noninvasive stress testing.

The study recruited 1,200 patients, about three-quarters male, with a median age of 62, of whom 14% had diabetes. More procedure-related MI occurred in the early invasive group, but after 10 years of follow-up there was no significant difference between the groups in risk of death or spontaneous MI.
“The current result confirms and extends the results of previous studies, with one-third of patients enduring death or spontaneous MI within 10 years despite treatment,” the authors wrote.

“We conclude that a strategy of selective invasive management is an option for selected patients. Not everyone with a positive troponin needs to be rushed to the cath lab,” coauthor Dr. R.J. de Winter, of the Academic Medical Center in Amsterdam told Reuters Health by email.

The authors point out that their findings contrast with the long-term results of two other studies (FRISC-II and RITA-3), “where a benefit of an early invasive strategy was shown.”
To explain this disparity, they note that the trials “enrolled patients in different time periods, and there were differences in clinical practice.”

Further, they point out, in ICTUS, “revascularization during hospitalization was 76 percent in the early invasive group and 40 percent in selective invasive group compared with 76 percent in the early invasive group versus 14 percent in the noninvasive group of FRISC-II and 44 percent versus 10 percent in RITA-3.”

In an editorial, Dr. Anthony A. Bavry of the North Florida/South Georgia Veterans Health System, Malcom Randall VA Medical Center, Gainesville, Florida, noted that early revascularization occurred in 9 percent of the FRISC-II control group vs 40 percent of the ICTUS control group.

“The control arm in the former trial more closely resembled conservative therapy,” he wrote. “The greater the difference in the incidence of revascularization between treatment arms, the greater the magnitude of benefit from invasive therapy.”

“(T)he last decade taught us that invasive therapy reduces adverse ischemic events, including early and intermediate death, myocardial infarction, or urgent revascularization for unstable angina,” Bavry concluded. “Future research will need to refine the lowest risk patients who are appropriate for conservative therapy.”

Despite the important differences between the three trials in terms of inclusion criteria, study design, treatment methods and recruitment periods, which might have contributed to the differing results, the studies “reported comparable long-term mortality in patients treated by selective invasive and routine invasive strategies,” Dr. Robert Henderson of Nottingham University Hospitals in the UK told Reuters Health by email.

Moreover, he added, the trials all reported higher rates of the combined endpoint of death or MI in the routine invasive arm, which, ICTUS suggests, is due to procedure-related MI, which nonetheless “did not translate into an excess mortality over 10-15 years follow-up.”

The combined evidence from these three trials, Dr. Henderson said, “raises questions about the widespread use of the routine invasive strategy in the majority of patients with non-ST-segment elevation myocardial infarction, many of whom may not benefit substantially from invasive treatment.”

On the other hand, he continued, interventional practice has evolved substantially since these trials recruited patients and now includes, for example, second generation drug-eluting stents and novel antiplatelet regimens. Therefore, “it is possible that the results of a routine invasive strategy will have improved over the last decade,” though such a strategy is associated with risks and costs.

“An invasive approach is indicated in patients with hemodynamic instability or with persistent or recurrent myocardial ischemia, but for patients who remain stable after a single episode of ischemia, the role of routine invasive treatment is less certain, particularly if risk assessment suggests that the patient is at low risk of recurrent cardiovascular events,” concluded Dr. Henderson, who was not involved with ICTUS.

The trial was supported by the Interuniversity Cardiology Institute of the Netherlands, the Working Group on Cardiovascular Research of the Netherlands, and educational grants from Eli Lilly, Sanofi/Synthelabo, Sanofi, Pfizer, and Medtronic.