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WASHINGTON – Administering methylprednisolone to patients undergoing cardiac surgery with cardiopulmonary bypass did not reduce the risks of death or major morbidity at 30 days, but was associated with an increased risk of early postoperative myocardial infarction, in a randomized controlled trial of about 7,500 high-risk surgical patients.
Based on the results of the study, the Steroids in Cardiac Surgery (SIRS) trial, "methylprednisolone should not be administered prophylactically to high-risk patients undergoing cardiac surgery" with cardiopulmonary bypass, Dr. Richard Whitlock said at the annual meeting of the American College of Cardiology.
SIRS, a randomized controlled study, evaluated the effects of prophylactic steroids in patients undergoing cardiac surgery with cardiopulmonary bypass in 18 countries in North and South America, Europe, the Middle East, and Asia. The study addressed whether the use of prophylactic steroids can attenuate the "intense inflammatory response" that occurs with cardiopulmonary bypass and is associated with adverse outcomes, said Dr. Whitlock, a cardiac surgeon at McMaster University, Hamilton, Ont., and lead investigator in the study.
Whether this approach results in improved outcomes has been unclear, he said. A recent meta-analysis of 44 small studies suggested that steroids have clinical benefits in this setting, and this use of methylprednisolone is standard practice in many European countries. And although it is not used as extensively in the United States, it is still standard care at some U.S. centers, he noted.
In SIRS, patients were randomized to 500 mg methylprednisolone, administered intravenously during surgery (3,755 patients) or placebo (3,752). Patients were considered high risk; their mean age was 67 years, two-thirds were male, and their mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 7.1. Only one patient, who was in the treatment group, was lost to follow-up.
There were no significant differences between the two groups in the two primary endpoints: total mortality at 30 days and the combined endpoint of total mortality, stroke, MI, renal failure, or respiratory failure within 30 days. The results were consistent across different subgroups, including sex, diabetes status, age, EuroSCORE, type of surgery and duration of cardiopulmonary bypass.
However, significantly more patients in the treatment group had an MI – mostly early – after surgery (500 vs. 408 in the placebo group), an increased risk of 22%, which was statistically significant.
The use of methylprednisolone was not associated with an altered risk of other stroke, new renal failure, or respiratory failure, or other outcomes measured, including transfusion requirements, new-onset atrial fibrillation, length of ICU or hospital stay, surgical site infections, delirium, or GI complications, Dr. Whitlock said.
When asked about a possible mechanism behind the SIRS results, Dr. Whitlock said that one possible explanation could be that since one of the important early recovery strategies after myocardial injury is movement of glucose into cells, and insulin requirements increase in the steroid-treated patients, "it is possible that we’re inducing insulin resistance: Thereby, glucose is not entering the myocyte for the recovery phase after the ischemic insult." While that is plausible, he added, "we really don’t have the answer. What is important is the signal is clear, it’s clear across all subgroups, and it is a prognostically important increase."
Dr. Amit Khera, director of the preventive cardiology program at UT Southwestern Medical Center, Dallas, commented that SIRS was a definitive study, and this use of methylprednisolone, at least at higher doses, "should not be a strategy we should pursue."
The SIRS trial was conducted by the Population Health Research Institute at the Hamilton Health Sciences and McMaster University during 2007-2014 and was funded with grants from the Canadian Institutes for Health Research and the Canadian Network and Centre for Trials Internationally. Dr. Whitlock said he had no relevant financial disclosures.
WASHINGTON – Administering methylprednisolone to patients undergoing cardiac surgery with cardiopulmonary bypass did not reduce the risks of death or major morbidity at 30 days, but was associated with an increased risk of early postoperative myocardial infarction, in a randomized controlled trial of about 7,500 high-risk surgical patients.
Based on the results of the study, the Steroids in Cardiac Surgery (SIRS) trial, "methylprednisolone should not be administered prophylactically to high-risk patients undergoing cardiac surgery" with cardiopulmonary bypass, Dr. Richard Whitlock said at the annual meeting of the American College of Cardiology.
SIRS, a randomized controlled study, evaluated the effects of prophylactic steroids in patients undergoing cardiac surgery with cardiopulmonary bypass in 18 countries in North and South America, Europe, the Middle East, and Asia. The study addressed whether the use of prophylactic steroids can attenuate the "intense inflammatory response" that occurs with cardiopulmonary bypass and is associated with adverse outcomes, said Dr. Whitlock, a cardiac surgeon at McMaster University, Hamilton, Ont., and lead investigator in the study.
Whether this approach results in improved outcomes has been unclear, he said. A recent meta-analysis of 44 small studies suggested that steroids have clinical benefits in this setting, and this use of methylprednisolone is standard practice in many European countries. And although it is not used as extensively in the United States, it is still standard care at some U.S. centers, he noted.
In SIRS, patients were randomized to 500 mg methylprednisolone, administered intravenously during surgery (3,755 patients) or placebo (3,752). Patients were considered high risk; their mean age was 67 years, two-thirds were male, and their mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 7.1. Only one patient, who was in the treatment group, was lost to follow-up.
There were no significant differences between the two groups in the two primary endpoints: total mortality at 30 days and the combined endpoint of total mortality, stroke, MI, renal failure, or respiratory failure within 30 days. The results were consistent across different subgroups, including sex, diabetes status, age, EuroSCORE, type of surgery and duration of cardiopulmonary bypass.
However, significantly more patients in the treatment group had an MI – mostly early – after surgery (500 vs. 408 in the placebo group), an increased risk of 22%, which was statistically significant.
The use of methylprednisolone was not associated with an altered risk of other stroke, new renal failure, or respiratory failure, or other outcomes measured, including transfusion requirements, new-onset atrial fibrillation, length of ICU or hospital stay, surgical site infections, delirium, or GI complications, Dr. Whitlock said.
When asked about a possible mechanism behind the SIRS results, Dr. Whitlock said that one possible explanation could be that since one of the important early recovery strategies after myocardial injury is movement of glucose into cells, and insulin requirements increase in the steroid-treated patients, "it is possible that we’re inducing insulin resistance: Thereby, glucose is not entering the myocyte for the recovery phase after the ischemic insult." While that is plausible, he added, "we really don’t have the answer. What is important is the signal is clear, it’s clear across all subgroups, and it is a prognostically important increase."
Dr. Amit Khera, director of the preventive cardiology program at UT Southwestern Medical Center, Dallas, commented that SIRS was a definitive study, and this use of methylprednisolone, at least at higher doses, "should not be a strategy we should pursue."
The SIRS trial was conducted by the Population Health Research Institute at the Hamilton Health Sciences and McMaster University during 2007-2014 and was funded with grants from the Canadian Institutes for Health Research and the Canadian Network and Centre for Trials Internationally. Dr. Whitlock said he had no relevant financial disclosures.
WASHINGTON – Administering methylprednisolone to patients undergoing cardiac surgery with cardiopulmonary bypass did not reduce the risks of death or major morbidity at 30 days, but was associated with an increased risk of early postoperative myocardial infarction, in a randomized controlled trial of about 7,500 high-risk surgical patients.
Based on the results of the study, the Steroids in Cardiac Surgery (SIRS) trial, "methylprednisolone should not be administered prophylactically to high-risk patients undergoing cardiac surgery" with cardiopulmonary bypass, Dr. Richard Whitlock said at the annual meeting of the American College of Cardiology.
SIRS, a randomized controlled study, evaluated the effects of prophylactic steroids in patients undergoing cardiac surgery with cardiopulmonary bypass in 18 countries in North and South America, Europe, the Middle East, and Asia. The study addressed whether the use of prophylactic steroids can attenuate the "intense inflammatory response" that occurs with cardiopulmonary bypass and is associated with adverse outcomes, said Dr. Whitlock, a cardiac surgeon at McMaster University, Hamilton, Ont., and lead investigator in the study.
Whether this approach results in improved outcomes has been unclear, he said. A recent meta-analysis of 44 small studies suggested that steroids have clinical benefits in this setting, and this use of methylprednisolone is standard practice in many European countries. And although it is not used as extensively in the United States, it is still standard care at some U.S. centers, he noted.
In SIRS, patients were randomized to 500 mg methylprednisolone, administered intravenously during surgery (3,755 patients) or placebo (3,752). Patients were considered high risk; their mean age was 67 years, two-thirds were male, and their mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 7.1. Only one patient, who was in the treatment group, was lost to follow-up.
There were no significant differences between the two groups in the two primary endpoints: total mortality at 30 days and the combined endpoint of total mortality, stroke, MI, renal failure, or respiratory failure within 30 days. The results were consistent across different subgroups, including sex, diabetes status, age, EuroSCORE, type of surgery and duration of cardiopulmonary bypass.
However, significantly more patients in the treatment group had an MI – mostly early – after surgery (500 vs. 408 in the placebo group), an increased risk of 22%, which was statistically significant.
The use of methylprednisolone was not associated with an altered risk of other stroke, new renal failure, or respiratory failure, or other outcomes measured, including transfusion requirements, new-onset atrial fibrillation, length of ICU or hospital stay, surgical site infections, delirium, or GI complications, Dr. Whitlock said.
When asked about a possible mechanism behind the SIRS results, Dr. Whitlock said that one possible explanation could be that since one of the important early recovery strategies after myocardial injury is movement of glucose into cells, and insulin requirements increase in the steroid-treated patients, "it is possible that we’re inducing insulin resistance: Thereby, glucose is not entering the myocyte for the recovery phase after the ischemic insult." While that is plausible, he added, "we really don’t have the answer. What is important is the signal is clear, it’s clear across all subgroups, and it is a prognostically important increase."
Dr. Amit Khera, director of the preventive cardiology program at UT Southwestern Medical Center, Dallas, commented that SIRS was a definitive study, and this use of methylprednisolone, at least at higher doses, "should not be a strategy we should pursue."
The SIRS trial was conducted by the Population Health Research Institute at the Hamilton Health Sciences and McMaster University during 2007-2014 and was funded with grants from the Canadian Institutes for Health Research and the Canadian Network and Centre for Trials Internationally. Dr. Whitlock said he had no relevant financial disclosures.
AT ACC 14
Major finding: Intraoperative methylprednisolone had no prophylactic effect in reducing mortality or serious morbidity, but was associated with a 22% increased risk of early postoperative MI, in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass.
Data source: The SIRS trial, a randomized, controlled international study that compared 30-day all-cause mortality and a composite endpoint in more than 7,500 high risk patients undergoing cardiac surgery with cardiopulmonary bypass randomized to receive an intravenous dose of methylprednisolone or placebo.
Disclosures: SIRS was funded with grants from the Canadian Institutes for Health Research and the Canadian Network and Centre for Trials Internationally. Dr. Whitlock said he had no relevant financial disclosures.
