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Revascularization with coronary artery bypass graft (CABG) surgery is associated with increased risk of stroke both at 30 days and 1 year compared with percutaneous coronary intervention (PCI), according to a large meta-analysis published in the August 28, 2012, issue of the Journal of the American College of Cardiology. 

Investigators led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), assessed stroke rates following revascularization by analyzing 19 trials with 10,944 patients who were randomized to CABG (n = 5,448) or PCI (n = 5,496) for varying levels of CAD of severity.

PCI Favored at Both 30 Days, 1 Year

In an analysis including 14 of the trials with 8,744 patients, stroke at 30 days (the primary endpoint) was almost 3 times more frequent among patients treated with CABG than those who received PCI at 1.20% vs. 0.34%, respectively (OR 2.94; 95% CI 1.69-5.09; P < 0.0001). With an excess of 7 strokes for every 1,000 patients treated with CABG rather than PCI, the ‘number needed to harm’ was 155.

Although the risk of stroke increased with the extent of CAD, the relationship was not significant (P = 0.25). Nor was there an interaction between 30-day stroke risk and the type of PCI (ie, balloon angioplasty vs. stenting; P = 0.52).

In addition, an analysis limited to 12 of the studies involving 7,052 randomized patients showed that the difference in stroke favoring PCI over CABG was maintained at a median follow-up of 12.1 months (1.84% vs. 0.99%; OR 1.67; 95% CI 1.09-2.56; P = 0.02). Stroke risk rose with increasing extent of CAD but only in CABG patients, and the interaction was not significant (P = 0.08).

A similar pattern of higher stroke risk with CABG emerged from a separate analysis in the same paper of 27 observational studies with 33,980 patients. According to the authors, “the relative reduction in stroke with PCI compared with CABG was even more pronounced in these real-world studies, particularly at 30 days.”

Despite acknowledging multiple limitations, including an inability to analyze the influence of classic stroke risk factors or the relation between stroke and mortality, Dr. Stone and colleagues defend the importance of the study.

“The large number of patients included . . . and the satisfaction of all requirements for meta-analysis, in terms of low heterogeneity, absent publication bias, and sensitivity analysis, provide robust scientific validity to our findings,” they write. Furthermore, these data can “assist informed decision making by patients, their families, and physicians when deciding on the optimal strategy of revascularization in patients with severe CAD.”

Study Undermined by Outdated Surgery

In a telephone interview with TCTMD, Joseph F. Sabik III, MD, of the Cleveland Clinic (Cleveland, OH), said that while the paper is “interesting and provocative,” many of the trials included in the meta-analysis are outdated. “Today, bypass surgery has progressed so much that the risk of stroke has gone down despite the fact that the risk of the patients [undergoing surgery] has gone up,” he noted, citing a paper that tracked the Cleveland Clinic experience over 2 decades (Tarakji KG, et al. JAMA. 2011;305:381-390).

Most strokes associated with surgery occur when atherosclerotic plaque breaks off of the aorta when it is either cannulated or manipulated, Dr. Sabik explained, “so it’s very important when you do bypass surgery to assess the aorta, and we have tools today such as intraoperative epiaortic echo [to do that].

“In patients who are at high risk of stroke, we can do their surgery off pump without touching or clamping the aorta,” he continued. “Or we can do what we call on-pump beating-heart [surgery] where we don’t manipulate the aorta. We also have ways of connecting [grafts] to the aorta or [performing] multiple arterial grafting that again don’t manipulate the aorta.”

However, in an e-mail communication with TCTMD, study coauthor Tullio Palmerini, MD, of the Policlinico S. Orsola (Bologna, Italy), contended that the question of whether off-pump CABG reduces stroke risk compared with on-pump procedures remains controversial. In fact, he wrote, “2 recent meta-analyses have reported discrepant results.”

Another shortcoming of the analysis, Dr. Sabik suggested, is its inability to differentiate among types of strokes. “Were they small [defects] that by 2 weeks the patient was back to normal, or were they major strokes?” he wondered.

But Dr. Palmerini reported that “in most of the studies stroke was defined as an irreversible neurological deficit confirmed by a neurologist or by CT or MRI scanning.” Few of the studies included mortality rates subsequent to stroke, he acknowledged, adding that in the pooled studies reporting on clinical outcome after stroke, the incidence of mortality was 16%. The finding confirms “the significant impact of stroke shown in prior studies,” he asserted.

Surgery Mostly for Complex Disease

According to Dr. Sabik, the study’s failure to find a significant relationship between likelihood of stroke and extent of CAD is surprising and may reflect the patient populations being examined. “Even in SYNTAX, patients with extensive disease were deemed not to be appropriate for both PCI and surgery and went into a surgery registry,” he pointed out. “So the patients with the worst disease are already having surgery, and they’re not in these studies. Yet we see a direct correlation with the extent of disease when we look at surgical studies.”

Dr. Palmerini agreed that the study may have lacked the power to discern a significant association between CAD complexity and stroke risk. However, he noted, there was a “gradient of risk” in CABG patients, which was most apparent in those with left main disease.

Dr. Sabik said that “there are always going to be comorbidities that influence the risk of stroke, and how you deal with them in PCI or surgery is going to determine the outcome. That’s what doesn’t [come through] in this paper, because probably the vast majority of patients had [CABG] done on pump with an arrested heart, which is not what we would consider [standard] 2012 coronary surgery.”

If PCI were compared with state-of-the-art surgery, stroke rates for the 2 therapies would likely be equivalent, he speculated.

Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Related Stories:

• PCI-Related Stroke Rare, Tied to Modifiable Procedural Factors
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• Study Examines Influence of Baseline Factors on Outcomes After CABG, PCI