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Claims that off-pump coronary artery bypass (OPCAB) carries a lower risk of short-term stroke than conventional on-pump coronary artery bypass grafting (CABG) have been the subject of contradicting evidence, mostly because of the small size of the studies that showed a benefit, but European investigators published a meta-analysis involving more than 19,000 cases that showed what they called a “significant reduction” in the odds of a stroke.
“OPCAB was associated with a significant (28%) reduction in the odds of stroke compared with CABG,” said lead author Dr. Mariusz Kowalewski of Copernicus University in Bydgoszcz, Poland, and coauthors. The meta-analysis appeared in the January issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:60-77).
The coauthors represent 10 different centers throughout Europe. Dr. Kowalewski and three other coauthors are also with the Systemic Investigation and Research on Interventions and Outcomes MEDICINE Research Network based in Düsseldorf, Germany.
Dr. Kowalewski and colleagues said this is the largest meta-analysis of randomized clinical trials comparing short-term outcomes of the two approaches to coronary bypass. “By its unique design, this analysis is the first report to investigate the causal relationship between underlying patient risk profile and the benefits of off-pump coronary revascularization,” they noted.
The meta-analysis looked at results of three primary outcomes: death within 30 days of the operation (2.25% overall, 2% in the OPCAB group and 2.04% in the CABG group); MI 30 days after surgery (4.49% overall, 4.3% for OPCAB and 4.67% for CABG); and 30-day occurrence of stroke (1.67% overall, 1.34% for OPCAB group and 2% for CABG).
In the meta-analysis, the researchers evaluated 100 studies for potential bias and conducted three separate analyses: one of all studies; and then separate analyses of studies of more than 50 and 100 subjects, respectively. Their goal was to check if small studies were driving the results.
Dr. Kowalewski and the study team acknowledged the conflicting science surrounding the benefits of the off-pump vs. conventional bypass. They pointed out that a host of randomized studies failed to show significant differences in stroke rates between the two approaches, and that conflicting European and American guidelines on the role of off-pump surgery to provide a better neurologic outcome do not help to clarify the relative risk.
“This apparent contradiction with the available registries’ data reporting a significantly decreased incidence of stroke with OPCAB may be explained by the fact that cerebral stroke represents a relatively rare entity after CABG, and thus even the largest randomized studies are underpowered to prove a possible advantage of one technique over the other,” Dr. Kowalewski and colleagues said.
They cited the CORONARY trial (N Engl J Med. 2012;366:1489-97), the largest trial to date, with 4,752 patients, which found no difference in the rate of stroke between the two groups. Three previous meta-analyses demonstrated 30%-50% reductions in stroke, but a systemic review called those results into question (Cochrane Database Syst. Rev. 2012;3:CD007224).
The “most important” finding of their study may be the confirmation of what large registries have reported: that OPCAB is safer and more effective than conventional bypass surgery in older and sicker patients. But they acknowledged that why this is the case “remains a subject of ongoing debate.”
Dr. Kowalewski and coresearchers acknowledged a number of limitations of their meta-analysis, namely that sensitivity analysis may have missed clinically important differences in patient results and broad patient inclusion criteria. However, the random-effects model they used accounted for study variations. “The findings on significant risk profile meta-regression are further corroborated in the analysis of MI and stroke,” they said.
Coauthor Dr. Eliano Pio Navarese disclosed honoraria from Eli Lilly. The other coauthors had no relationships to disclose.
That off-pump coronary artery bypass (OPCAB) grafting provides no benefit or, at best, a negligible benefit over conventional on-pump surgery in terms of 30-day death rates and risk of myocardial infarction is a question that can be laid “safely to bed,” Dr. Fraser Rubens of the University of Ottawa Heart Institute said in his invited commentary (J Thorac Cardiovasc Surg. 2016;151:78-9).
However, less clear cut is the meta-analysis researchers’ assertion that off-pump CABG can significantly reduce the risk of future stroke, and that requires a close examination of the structural shortcomings of any meta-analysis, Dr. Rubens said. He cited a report that stated meta-analyses may inaccurately predict the outcomes of subsequent large randomized clinical trials in about one-third of all cases (N Engl J Med 1997;337:536-42).
Smaller trials like those used in a meta-analysis are more likely to be flawed because of a lax peer review or compromised methodology, Dr. Rubens said. The largest randomized trial the authors used in the meta-analysis showed “certainly no difference in stroke,” and when all trials with 200 or fewer patients were excluded, the stroke rates were 1.4% in the off-pump group vs. 1.6% in the on-pump population, he said.
To validate that difference would require a number needed to treat of 500 patients to prevent one stroke, Dr. Rubens said, “and the sample size required to prove this difference would exceed 58,000 patients per group” – whereas the large-trial cohort in this meta-analysis population was about a tenth of that.
“One must therefore assimilate this information with the worrisome evidence that off-pump surgery is associated with an increased incidence of incomplete revascularization, which is likely related to the subsequent increased need for repeat revascularization,” Dr. Rubens said.
Dr. Rubens had no disclosures.
That off-pump coronary artery bypass (OPCAB) grafting provides no benefit or, at best, a negligible benefit over conventional on-pump surgery in terms of 30-day death rates and risk of myocardial infarction is a question that can be laid “safely to bed,” Dr. Fraser Rubens of the University of Ottawa Heart Institute said in his invited commentary (J Thorac Cardiovasc Surg. 2016;151:78-9).
However, less clear cut is the meta-analysis researchers’ assertion that off-pump CABG can significantly reduce the risk of future stroke, and that requires a close examination of the structural shortcomings of any meta-analysis, Dr. Rubens said. He cited a report that stated meta-analyses may inaccurately predict the outcomes of subsequent large randomized clinical trials in about one-third of all cases (N Engl J Med 1997;337:536-42).
Smaller trials like those used in a meta-analysis are more likely to be flawed because of a lax peer review or compromised methodology, Dr. Rubens said. The largest randomized trial the authors used in the meta-analysis showed “certainly no difference in stroke,” and when all trials with 200 or fewer patients were excluded, the stroke rates were 1.4% in the off-pump group vs. 1.6% in the on-pump population, he said.
To validate that difference would require a number needed to treat of 500 patients to prevent one stroke, Dr. Rubens said, “and the sample size required to prove this difference would exceed 58,000 patients per group” – whereas the large-trial cohort in this meta-analysis population was about a tenth of that.
“One must therefore assimilate this information with the worrisome evidence that off-pump surgery is associated with an increased incidence of incomplete revascularization, which is likely related to the subsequent increased need for repeat revascularization,” Dr. Rubens said.
Dr. Rubens had no disclosures.
That off-pump coronary artery bypass (OPCAB) grafting provides no benefit or, at best, a negligible benefit over conventional on-pump surgery in terms of 30-day death rates and risk of myocardial infarction is a question that can be laid “safely to bed,” Dr. Fraser Rubens of the University of Ottawa Heart Institute said in his invited commentary (J Thorac Cardiovasc Surg. 2016;151:78-9).
However, less clear cut is the meta-analysis researchers’ assertion that off-pump CABG can significantly reduce the risk of future stroke, and that requires a close examination of the structural shortcomings of any meta-analysis, Dr. Rubens said. He cited a report that stated meta-analyses may inaccurately predict the outcomes of subsequent large randomized clinical trials in about one-third of all cases (N Engl J Med 1997;337:536-42).
Smaller trials like those used in a meta-analysis are more likely to be flawed because of a lax peer review or compromised methodology, Dr. Rubens said. The largest randomized trial the authors used in the meta-analysis showed “certainly no difference in stroke,” and when all trials with 200 or fewer patients were excluded, the stroke rates were 1.4% in the off-pump group vs. 1.6% in the on-pump population, he said.
To validate that difference would require a number needed to treat of 500 patients to prevent one stroke, Dr. Rubens said, “and the sample size required to prove this difference would exceed 58,000 patients per group” – whereas the large-trial cohort in this meta-analysis population was about a tenth of that.
“One must therefore assimilate this information with the worrisome evidence that off-pump surgery is associated with an increased incidence of incomplete revascularization, which is likely related to the subsequent increased need for repeat revascularization,” Dr. Rubens said.
Dr. Rubens had no disclosures.
Claims that off-pump coronary artery bypass (OPCAB) carries a lower risk of short-term stroke than conventional on-pump coronary artery bypass grafting (CABG) have been the subject of contradicting evidence, mostly because of the small size of the studies that showed a benefit, but European investigators published a meta-analysis involving more than 19,000 cases that showed what they called a “significant reduction” in the odds of a stroke.
“OPCAB was associated with a significant (28%) reduction in the odds of stroke compared with CABG,” said lead author Dr. Mariusz Kowalewski of Copernicus University in Bydgoszcz, Poland, and coauthors. The meta-analysis appeared in the January issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:60-77).
The coauthors represent 10 different centers throughout Europe. Dr. Kowalewski and three other coauthors are also with the Systemic Investigation and Research on Interventions and Outcomes MEDICINE Research Network based in Düsseldorf, Germany.
Dr. Kowalewski and colleagues said this is the largest meta-analysis of randomized clinical trials comparing short-term outcomes of the two approaches to coronary bypass. “By its unique design, this analysis is the first report to investigate the causal relationship between underlying patient risk profile and the benefits of off-pump coronary revascularization,” they noted.
The meta-analysis looked at results of three primary outcomes: death within 30 days of the operation (2.25% overall, 2% in the OPCAB group and 2.04% in the CABG group); MI 30 days after surgery (4.49% overall, 4.3% for OPCAB and 4.67% for CABG); and 30-day occurrence of stroke (1.67% overall, 1.34% for OPCAB group and 2% for CABG).
In the meta-analysis, the researchers evaluated 100 studies for potential bias and conducted three separate analyses: one of all studies; and then separate analyses of studies of more than 50 and 100 subjects, respectively. Their goal was to check if small studies were driving the results.
Dr. Kowalewski and the study team acknowledged the conflicting science surrounding the benefits of the off-pump vs. conventional bypass. They pointed out that a host of randomized studies failed to show significant differences in stroke rates between the two approaches, and that conflicting European and American guidelines on the role of off-pump surgery to provide a better neurologic outcome do not help to clarify the relative risk.
“This apparent contradiction with the available registries’ data reporting a significantly decreased incidence of stroke with OPCAB may be explained by the fact that cerebral stroke represents a relatively rare entity after CABG, and thus even the largest randomized studies are underpowered to prove a possible advantage of one technique over the other,” Dr. Kowalewski and colleagues said.
They cited the CORONARY trial (N Engl J Med. 2012;366:1489-97), the largest trial to date, with 4,752 patients, which found no difference in the rate of stroke between the two groups. Three previous meta-analyses demonstrated 30%-50% reductions in stroke, but a systemic review called those results into question (Cochrane Database Syst. Rev. 2012;3:CD007224).
The “most important” finding of their study may be the confirmation of what large registries have reported: that OPCAB is safer and more effective than conventional bypass surgery in older and sicker patients. But they acknowledged that why this is the case “remains a subject of ongoing debate.”
Dr. Kowalewski and coresearchers acknowledged a number of limitations of their meta-analysis, namely that sensitivity analysis may have missed clinically important differences in patient results and broad patient inclusion criteria. However, the random-effects model they used accounted for study variations. “The findings on significant risk profile meta-regression are further corroborated in the analysis of MI and stroke,” they said.
Coauthor Dr. Eliano Pio Navarese disclosed honoraria from Eli Lilly. The other coauthors had no relationships to disclose.
Claims that off-pump coronary artery bypass (OPCAB) carries a lower risk of short-term stroke than conventional on-pump coronary artery bypass grafting (CABG) have been the subject of contradicting evidence, mostly because of the small size of the studies that showed a benefit, but European investigators published a meta-analysis involving more than 19,000 cases that showed what they called a “significant reduction” in the odds of a stroke.
“OPCAB was associated with a significant (28%) reduction in the odds of stroke compared with CABG,” said lead author Dr. Mariusz Kowalewski of Copernicus University in Bydgoszcz, Poland, and coauthors. The meta-analysis appeared in the January issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:60-77).
The coauthors represent 10 different centers throughout Europe. Dr. Kowalewski and three other coauthors are also with the Systemic Investigation and Research on Interventions and Outcomes MEDICINE Research Network based in Düsseldorf, Germany.
Dr. Kowalewski and colleagues said this is the largest meta-analysis of randomized clinical trials comparing short-term outcomes of the two approaches to coronary bypass. “By its unique design, this analysis is the first report to investigate the causal relationship between underlying patient risk profile and the benefits of off-pump coronary revascularization,” they noted.
The meta-analysis looked at results of three primary outcomes: death within 30 days of the operation (2.25% overall, 2% in the OPCAB group and 2.04% in the CABG group); MI 30 days after surgery (4.49% overall, 4.3% for OPCAB and 4.67% for CABG); and 30-day occurrence of stroke (1.67% overall, 1.34% for OPCAB group and 2% for CABG).
In the meta-analysis, the researchers evaluated 100 studies for potential bias and conducted three separate analyses: one of all studies; and then separate analyses of studies of more than 50 and 100 subjects, respectively. Their goal was to check if small studies were driving the results.
Dr. Kowalewski and the study team acknowledged the conflicting science surrounding the benefits of the off-pump vs. conventional bypass. They pointed out that a host of randomized studies failed to show significant differences in stroke rates between the two approaches, and that conflicting European and American guidelines on the role of off-pump surgery to provide a better neurologic outcome do not help to clarify the relative risk.
“This apparent contradiction with the available registries’ data reporting a significantly decreased incidence of stroke with OPCAB may be explained by the fact that cerebral stroke represents a relatively rare entity after CABG, and thus even the largest randomized studies are underpowered to prove a possible advantage of one technique over the other,” Dr. Kowalewski and colleagues said.
They cited the CORONARY trial (N Engl J Med. 2012;366:1489-97), the largest trial to date, with 4,752 patients, which found no difference in the rate of stroke between the two groups. Three previous meta-analyses demonstrated 30%-50% reductions in stroke, but a systemic review called those results into question (Cochrane Database Syst. Rev. 2012;3:CD007224).
The “most important” finding of their study may be the confirmation of what large registries have reported: that OPCAB is safer and more effective than conventional bypass surgery in older and sicker patients. But they acknowledged that why this is the case “remains a subject of ongoing debate.”
Dr. Kowalewski and coresearchers acknowledged a number of limitations of their meta-analysis, namely that sensitivity analysis may have missed clinically important differences in patient results and broad patient inclusion criteria. However, the random-effects model they used accounted for study variations. “The findings on significant risk profile meta-regression are further corroborated in the analysis of MI and stroke,” they said.
Coauthor Dr. Eliano Pio Navarese disclosed honoraria from Eli Lilly. The other coauthors had no relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Off-pump coronary artery bypass is associated with a significant reduction in the odds of stroke compared with conventional coronary artery bypass grafting and should be considered in high-risk patients.
Major finding: Off-pump coronary artery bypass was associated with a 28% reduction in the odds of patients having a cerebral stroke when compared with the conventional on-pump procedure.
Data source: Meta-analysis of 100 studies with a total of 19,192 patients.
Disclosures: Coauthor Dr. Eliano Pio Navarese disclosed honoraria from Eli Lilly. The other authors had no relationships to disclose.