Substudy Suggests Invasive Strategy Better for Elderly NSTE-ACS Patients
An invasive strategy during the index hospitalization of elderly patients with NSTE-ACS improves clinical outcomes at 1 year, according to an as-treated subanalysis of the Italian Elderly ACS study published online December 17, 2014, ahead of print in the American Journal of Cardiology.
The original Elderly ACS study showed that randomization to an early aggressive therapy compared with an early conservative strategy did not confer a lower composite risk of MI, death, stroke, and rehospitalization at 1 year in patients 75 years or older with NSTE-ACS.
For the current subanalysis, Gennaro Galasso, MD, PhD, of Federico II University of Naples (Naples, Italy), and colleagues analyzed the as-treated data of 313 patients who received angiography during the initial hospitalization (n = 182) and those who were solely medically managed (n = 131), regardless of their initial treatment assignment.
Baseline characteristics and prognostic risk factors were well balanced between the invasive and conservative groups, except for older age and lower hemoglobin levels in the conservative cohort. Length of hospital stay; rate of adverse events during hospitalization; and pharmacological treatment at discharge, apart from a higher use of nitrates and diuretics in the conservative group, were similar. Importantly, invasive treatment was not associated with an increased rate of death or procedure-related MI during admission.
Fewer Events With Invasive Treatment
One-quarter of patients (n = 46) originally randomized to medical management received coronary angiography due to the presence of refractory ischemia (n = 37), reinfarction (n = 1), heart failure of ischemic origin (n = 6), or sustained ventricular tachycardia (n = 2). Of those patients, 36 received subsequent revascularization.
Overall, more than 60% of patients who were revascularized received PCI (n = 111) and 5.5% received CABG (n = 10).
The primary endpoint—all-cause mortality, nonfatal MI, disabling stroke, and rehospitalization for cardiovascular causes or severe bleeding within 1 year—occurred less often in the invasive than in the conservative cohort. Patients treated invasively also had lower rates of nonfatal MI, combined death and MI, and bleeding (table 1).
Kaplan-Meier estimates confirmed lower rates of combined death and MI and the primary endpoint for the invasively treated patients. Moreover, on Cox regression analysis, invasive treatment was the most important predictor of event-free survival (HR 0.55; 95% CI 0.37-0.82), which remained the case after multivariate adjustment (HR 0.59; 95% CI 0.39-0.88).
Dr. Galasso and colleagues write that their results are in line with those of “10 randomized trials show[ing] a significant improvement in survival free from myocardial infarction, recurrent cardiac ischemia, and rehospitalization” with invasive treatment. Early invasive treatment, however, appears to impart a survival benefit for high-risk but not low-risk patients.
“Paradoxically,” Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in a telephone interview, “we tend to take to the cath lab patients who are relatively healthy, in which we think we can get good outcomes. And we don’t take to the cath lab the ones who benefit the most, meaning [those with] the most hemodynamic [compromise] or the larger infarct and more comorbidities.”
Results Not ‘Practice Changing’
Also in a telephone interview, Robert A. Henderson, MD, of Nottingham University Hospitals (Nottingham, England), called into question the subanalysis’ methodology. An as-treated analysis “is not terribly meaningful,” he said, because it could be that people who receive revascularization are highly selected and as such, could be a lower-risk cohort with lower subsequent event rates. “It may be purely that you have a difference here because of case selection, rather than because of any meaningful difference in outcomes between the 2 strategies.”
Dr. Brener agreed, adding, “[t]hat is why we do randomized trials—so we can analyze based on an intention-to-treat basis rather than a postrandomization decision where we don’t know how or why it was [made].” For example, he continued that “heart failure was a reason to go from invasive to conservative as well as from conservative to invasive. So obviously there was something else going on that we don’t know about.”
Additionally, Dr. Brener pointed out, “The most common reason for switching from the conservative to invasive [group] was recurrent ischemic events,” which is a valid treatment choice. Thus, these data should not be used to conclude that an initially conservative approach is bad. “So, it is really somewhat of a nonsensical analysis,” he concluded.
Dr. Henderson noted that the actual differences in various outcomes between the 2 cohorts were small (eg, a difference of 4 rehospitalizations, 6 myocardial infarctions, and 3 bleeding incidents) but still reached significance both individually and as the composite primary endpoint. “I would be very suspicious of the validity of that given the overall power of the trial and that they have this multiple endpoint composite primary endpoint,” he cautioned.
Dr. Brener said “that the more correct conclusion of this analysis would have been: patients who are selected by their physicians to undergo an invasive strategy do better than patients who are selected to undergo a conservative strategy.”
Overall, Dr. Henderson concluded, “[the study] certainly won’t influence my clinical practice because it is substantially underpowered, not a randomized analysis, and based on a rather dubious composite endpoint.”
Galasso G, De Servi S, Savonitto S, et al. Effect of an invasive strategy on outcome in patients ≥ 75 years of age with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2014;Epub ahead of print.
- The paper does not contain a statement regarding conflicts of interest for Dr. Galasso.
- Dr. Brener reports no relevant conflicts of interest.
- Dr. Henderson reports being an executive committee member of the RITA-3 trial, acting on the advisory board for a novel diagnostic technology for ACS, and acting as a member of the development group that produced the UK NICE NSTEMI guideline in 2010 and deputy chair of the NICE STEMI guideline in 2013.