TORONTO, ON — Coronary artery bypass graft (CABG) surgery is superior to PCI for reducing the risk of all-cause mortality in diabetic patients with multivessel disease, according to the results of a new meta-analysis.
Treating diabetic patients with surgery significantly reduced the risk of death by one-third at five years compared with PCI, and there was no difference in benefit if PCI was performed with a bare-metal stent or drug-eluting stent (DES), report investigators.
"The discussion and debate around PCI vs CABG in diabetes is always stalled because there have been questions about whether mortality is any different between the two procedures," said lead investigator Dr Subodh Verma (St Michael's Hospital, Toronto, ON). "If you look at the strength of this analysis, it provides robust statistical power to suggest a highly significant reduction in all-cause mortality by 33% at five years in diabetics. It comes to a very important conclusion that has not had previous clarity, and that is there is clearly a mortality benefit. And in the world in which we live, all-cause mortality trumps everything."
The results of the study were published September 12, 2013 in the Lancet.
Findings in Line With FREEDOM
The findings closely mirror the results of the large-scale Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial, published in 2012. Presented at the American Heart Association 2012 Scientific Sessions and reported by heartwire, study investigators showed that patients with diabetes and multivessel coronary artery disease treated with CABG surgery had significantly lower rates of death from any cause, nonfatal MI, or nonfatal stroke compared with PCI-treated patients.
The FREEDOM study was not powered for all-cause mortality, but investigators did report a borderline reduction in risk of all-cause mortality among patients randomized to cardiac surgery. The strength of the present analysis, said Verma, is that it combines multiple studies, including contemporary trials using newer-generation stents, to assess the effect of revascularization procedures on mortality.
"Although FREEDOM showed the benefit of drug-eluting stents over bypass surgery, mortality was only a secondary outcome, and it just barely made statistical significance," said Verma. "It was at odds with a number of smaller studies in which mortality was not necessarily different. Since the publication of FREEDOM, the results of other trials, although small and underpowered--yet randomized and well conducted--have been made available. And as far I know, there is nothing on the horizon that will be randomizing diabetic patients to PCI vs CABG."
The meta-analysis included four randomized controlled trials ERACI II , ARTS , SOS , and MASS II), which compared CABG with PCI using bare-metal stents, and four studies (FREEDOM, SYNTAX , VA-CARDS , and CARDIA ) comparing cardiac surgery vs PCI using DES. In these eight studies, there were 7468 participants, including 3612 with diabetes. All but the VA-CARDS study reported five-year clinical outcomes, and VA-CARDS had mortality data out to two years.
Treatment with CABG significantly reduced the risk of all-cause mortality by 33% compared with PCI in diabetic patients. In a subanalysis, the reduction in all-cause mortality in the bare-metal-stent group was not statistically significant. Looking only at the DES trials, there was a significant 35% reduction in risk of all-cause mortality favoring CABG. However, an interaction test showed that the relative risk reduction for CABG vs bare-metal-stent or DES subgroups did not differ significantly, report investigators.
The benefit of CABG over PCI at five years was observed only in patients with diabetes.
All-Cause Mortality at Five-Year Follow-up
|Comparator vs CABG*||CABG deaths in diabetic patients, n||PCI deaths in diabetic patients, n||Relative risk reduction (95% CI)|
|Bare-metal stent||22||35||0.70 (0.40-1.24)|
The reduction in all-cause mortality was not observed at one year. The need for repeat revascularization was significantly lower at one year, as well as at five years, among patients treated with CABG compared with PCI-treated patients. Stroke risk was higher with surgery, but the increased risk occurred mainly in the first year of follow-up. The risk of nonfatal MI was difficult to determine, say investigators, because of the different definitions used in the trials.
To heartwire , Verma said that the burden of atherosclerosis in diabetic patients, as well as the diffuse nature of their disease, makes CABG a better option because surgery bypasses the diseased vessel rather than revascularize a culprit lesion. "With surgery, you bypass many more of these potentially vulnerable plaques, and this might be one of the reasons why a more complete revascularization strategy is effective," he said.
In the analysis, the benefit of surgery over PCI was observed in diabetic patients with low, intermediate, and high SYNTAX scores, which also suggests there might be "something unique" about the diabetic patient, added Verma.
A Challenging Patient Population
Dr Robert Byrne (Deutsches Herzzentrum, Munich, Germany), an interventional cardiologist at a high-volume center who commented on the findings, said diabetic patients remain a challenging population to treat. The evidence to date has suggested an advantage of CABG over PCI, and the meta-analysis confirms this. However, Byrne noted that the technology is constantly changing, with stent technology continuing to evolve, and he would like to see how CABG stacks up against the latest DES. Newer DES not only reduce restenosis, but also reduce vessel occlusion compared with the stents used in the meta-analysis.
Also commenting on the results for heartwire , Dr Ted Bass (University of Florida, Jacksonville), president of the Society for Angiography and Cardiovascular Interventions, said he wasn't surprised by the findings, noting that the results are in line with the FREEDOM trial. "The study reinforces some evidence that's already been out there," said Bass. "In diabetics, all things being equal, there seems to be a downstream clinical benefit in large populations treated with CABG vs populations treated with PCI."
Still, Bass said what it is not known from the meta-analysis is the extent of revascularization among the PCI-treated patients and whether or not this affects the results. Moreover, he sees some positive data for patients without diabetes, noting that the benefit of CABG over PCI is nullified in those without the metabolic disorder. If a stroke advantage exists with PCI in this nondiabetic cohort, then PCI looks like an attractive option.
"If there is an increase in stroke risk, and no decrease in mortality among the nondiabetic patients, and we don't have any information on nonfatal MI, I think you can hypothesize that maybe multivessel PCI in appropriately selected patients who are not diabetics is even better than many had thought," said Bass.
Verma, Byrne, and Bass all stressed the importance of providing diabetic patients who require revascularization unbiased evidence to help them make the best treatment decision.
Heartwire from Medscape © 2013
Cite this: CABG Reduces Risk of Death vs PCI in Diabetic Patients - Medscape - Sep 13, 2013.