Meta-analysis: Mortality Lower With PCI vs Medical Therapy Alone in Stable Patients With Documented Ischemia
It remains unclear whether PCI holds an edge over optimal medical therapy (OMT) for hard outcomes like death and MI in patients with stable ischemic heart disease, but a meta-analysis published online February 11, 2015, ahead of print in the American Journal of Cardiology hints that PCI offers a lower mortality risk in patients with objective evidence of ischemia.
Investigators led by Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), examined data from 3 randomized controlled trials—FAME II, SWISSI II, and COURAGE Nuclear Substudy 0—that included a total of 1,557 patients, of whom all had documented ischemia and were randomized to PCI plus OMT or OMT alone.
Mean age in the studies ranged from 54 to 64 years, and FAME 2 had the largest percentage of women, who represented 20% of group given PCI plus OMT and 23% of the group given OMT alone in that trial.
Over a mean follow-up of 3 years, pooled mortality rates were 3.0% for patients undergoing PCI plus OMT and 5.9% for those who received OMT alone. Each individual trial showed the mortality difference, although it became significant only in the overall random effects analysis (table 1).
There was no heterogeneity among the studies and no evidence of bias (P = .46 by Egger’s test).
Potential Signals Require Study
In an interview with TCTMD, Dr. Kirtane noted that the mortality finding “is purely hypothesis generating,” as the analysis is underpowered for that endpoint.
“No one should definitively conclude that we are reducing mortality by doing PCI, but we should at least be thinking about it. And this is something that is certainly worth studying, which is why the ISCHEMIA trial is being done,” he said. “There are signals in the literature that if you take high-risk individuals and revascularize them, you can improve their prognosis.”
Asked if the potential for a PCI advantage could discourage some clinicians from enrolling patients in ISCHEMIA, Dr. Kirtane acknowledged that it is possible. However, he emphasized, “if there were no evidence that there might be a benefit, then it frankly wouldn't make sense to do the ISCHEMIA trial—a trial for which the primary hypothesis is that an invasive approach to [stable ischemic heart disease] can reduce hard clinical outcomes.”
Both the main COURAGE trial and BARI 2D showed no difference between PCI and OMT alone in the primary outcome of all-cause death or nonfatal MI in patients with stable ischemic heart disease. However, both of those trials randomized patients after cardiac catheterization, whereas ISCHEMIA is first using coronary CTA to exclude patients with minimal atherosclerotic disease and then randomizing those with at least moderate ischemia on stress imaging to invasive or conservative treatment.
Dr. Kirtane added that even though the benefit of revascularization may have been over-extrapolated in some studies, “you don’t throw the baby out with the bathwater.
“What we need to do is figure out which patients are high risk enough that they might [see] benefits that go beyond just symptom relief,” he continued. Although the reasons are unclear, a possible explanation, he noted, is that revascularization prevents prognostically important spontaneous MIs.
All Eyes on ISCHEMIA
In an email with TCTMD, Somjot S. Brar, MD, MPH, of Kaiser Permanente (Los Angeles, CA), said the meta-analysis is “encouraging because the studies included are generally similar and the treatment effects are also comparable across studies.”
Agreeing with the study authors that the results “represent an underpowered estimate of the potential treatment effect,” he added that the data “should encourage participation in the ISCHEMIA trial so that we may have answers sooner rather than later of PCI vs medical therapy in this vulnerable population.”
Leslee Shaw, PhD, of Emory University School of Medicine (Atlanta, GA), also highlighted ISCHEMIA.
“The ISCHEMIA trial really is the last hope for a very big trial to prove the benefit of a catheterization-driven strategy,” she told TCTMD in a telephone interview. “To my way of thinking, this [meta-analysis] is an impetus to enroll more patients into the trial, because we believe that doing so will take this hypothesis over the edge… and put this to rest once and for all.”
While the ISCHEMIA investigators believe that the trial will “turn the corner” toward ischemia-guided intervention, Dr. Shaw said, it also could end up “showing us that the signal is not real [and is] simply meta-analytic.”
Additionally, she said, the trial has the potential to shed the brightest light to date on medical therapy in these patients by conducting careful follow-up.
“In some cases, we are asking people to do a complete paradigm shift in terms of their lifestyle and… to take an average of 5 or 6 medications, to exercise, and to diet,” Dr. Shaw noted. “We all know that the average American doesn’t do a good job when asked to do these things, so that will be very interesting also once ISCHEMIA is completed.”
Note: Dr. Kirtane and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.
Gada H, Kirtane AJ, Kereiakes DJ, et al. Meta-analysis of trials on mortality after percutaneous coronary intervention compared with medical therapy in patients with stable coronary heart disease and objective evidence of myocardial ischemia. Am J Cardiol. 2015;Epub ahead of print.
Dr. Kirtane reports receiving institutional research grants from Abbott Vascular, Abiomed, Boston Scientific, Eli Lilly, Medtronic, St. Jude Medical, and Vascular Dynamics.
Dr. Brar reports no relevant conflicts of interest.