Meta-analysis: PCI Adds No Benefit to Medical Therapy in Patients with Proven Ischemia

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For patients with stable obstructive coronary artery disease (CAD) and objective evidence of myocardial ischemia, adding percutaneous coronary intervention (PCI) to medical therapy does not reduce the risk of death or other outcomes compared with medical therapy alone, according to a meta-analysis published online December 2, 2013, ahead of print in JAMA: Internal Medicine.

David L. Brown, MD, of the State University of New York-Stony Brook School of Medicine (Stony Brook, NY), and colleagues looked at 5,286 patients (4,064 of whom were diagnosed with myocardial ischemia), from 5 trials conducted between 1997 and 2012:

• MASS II
• Hambrecht et al
• COURAGE
• BARI 2D
• FAME 2

Of the patients with documented ischemia, 49.6% were randomized to PCI with medical therapy (n = 2,016) and the rest to medical therapy alone (n = 2,048). Stents were used in 66-100% of patients depending on the study; and DES were used in 37% and 95% of patients in the BARI 2D and FAME 2 studies, respectively. Medical therapy included aspirin, beta blockers, ACE inhibitors, and statins.

After a median follow-up of 5 years, there were no differences in rates of mortality, unplanned repeat revascularization, or angina between the study arms, although there was a trend toward more nonfatal MI in the PCI arm (table 1).

Table 1. Clinical Outcomes: PCI Plus Medical Therapy vs. Medical Therapy Alone

Excluding the MASS II data from the analysis resulted in a significant benefit of PCI vs. medical therapy alone in terms of repeat revascularization (OR 0.49; 95% CI 0.26-0.91; P = 0.02). However, removing FAME 2 data did not alter any results.

No Support for PCI

“These findings are unique in that this is the first meta-analysis to our knowledge limited to patients with documented, objective findings of myocardial ischemia, almost all of whom underwent treatment with intracoronary stents and disease-modifying secondary prevention therapy,” Dr. Brown and colleagues write.

The implications are threefold, they continue, as “the results strongly suggest that the relationship between ischemia and mortality is not altered or ameliorated by catheter-based revascularization of obstructive, flow-limiting coronary stenoses. Second, the lack of clinical benefit from PCI in patients with inducible ischemia suggests that the genesis of late clinical events is not necessarily a consequence of the ischemic vascular territory subtending a stenotic coronary segment but rather due to the development of new plaque ruptures in distant coronary segments without flow-limiting stenoses.”

Lastly, the analysis questions the “common practice of ischemia-guided revascularization (either using noninvasive testing techniques or FFR) where the presence of myocardial ischemia routinely determines patient selection for coronary angiography and revascularization,” the authors explain.

As such, the findings reinforce current clinical guidelines that recommend initial medical therapy rather than proceeding directly to ischemia-guided PCI, they conclude.

Unique Analysis, Insubstantial Results

Even given the results, David J. Cohen, MD, of Saint Luke’s Mid America Heart Institute (Kansas City, MO), told TCTMD in a telephone interview that “we still don’t know whether correcting myocardial ischemia will save lives in patients with coronary disease. . . . It is very well recognized that the greater degree of ischemia, the higher the clinical event rate and mortality in patients with coronary disease, but it’s not well established whether correcting the ischemia reverses that problem or whether the ischemia is just a marker of more extensive atherosclerosis. I think both are plausible hypotheses and deserve to be tested in a proper randomized trial.”

Part of the problem with this meta-analysis is the relatively small number of patients, which begets wide confidence intervals, according to Michael E. Farkouh, MD, MSc, of Mount Sinai School of Medicine (New York, NY). “We just need more numbers,” he told TCTMD in a telephone interview, adding that a benefit of the study was the inclusion of patients with demonstrated ischemia only. “[The study authors] tried to answer the right question.”

Dr. Cohen said the study “reinforces the need for the [ongoing] ISCHEMIA trial and should help people to have the proper amount of clinical equipoise. That trial is a very challenging trial for many investigators to enroll their patients in because they are already convinced that correcting the ischemia is the right thing to do. This paper makes a strong case that we don’t know the answer. It doesn’t prove anything, but . . . we should be appropriately skeptical as to whether correcting ischemia will change the natural history of coronary disease.”

The only surprise in the data came from the angina findings, he added. “This study would suggest that even revascularizing patients with ischemia doesn’t change angina, and I have a lot of trouble believing that,” Dr. Cohen said. While PCI might not provide long-term benefits, most patients care more about the short-term “and in those time frames the revascularization is clearly beneficial compared with medical therapy,” he added.

Ischemia Needs Quantification

On the other hand, Jeffrey W. Moses, MD, of Columbia University Medical Center/Weill Cornell Medical Center (New York, NY), told TCTMD in a telephone interview that “the question they are asking is not addressed by the study.” Since the majority of cardiologists assume that “patients with moderate to severe ischemia most likely have a benefit from revascularization even in the absence of symptoms,” he said, the inclusion criteria of the meta-analysis “are by and large simply the question of whether [patients] had any EKG changes on a stress test, which is not the same thing.”

Dr. Moses questioned the study authors’ methods in including patients from the different trials. For example, they included almost 90% of the patients in the COURAGE trial even though the nuclear substudy showed that less than one-third of them had even moderate ischemia, he noted. “So how do you get almost the entire study included? We know that the COURAGE study was a low ischemic group. The incredibly broad-based criteria for defining ischemia is not what most of us are discussing. Most of us are discussing image-based quantification or semi-quantification of the amount of ischemia, and that’s what the conversation is about.”

In the interim before the ISCHEMIA trial is completed, Dr. Moses said he “would love to see an analysis of patients with quantified or semi-quantified ischemia, as opposed to this study, which basically included patients with undefined ischemia, probably the vast majority with mild ischemia.”

 

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Source:
Stergiopoulos K, Boden WE, Hartigan P, et al. Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: A collaborative meta-analysis of contemporary randomized clinical trials. JAMA Intern Med. 2013;Epub ahead of print.

 

• Dr. Cohen reports receiving research grant support from multiple device manufacturers.

 

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