Beta-Blockers for Surgical Patients Linked to Increases in Stroke and Mortality
By Peggy Peck
HAMILTON, Ontario, 14 may 2008-- High-dose extended release metoprolol (Toprol XL) just before, shortly after, and for a month following non-cardiac surgery increased the risk of stroke and death within 30 days, researchers here reported.But the beta-blocker therapy reduced the number of non-fatal heart attacks and cardiac arrests, Philip J. Devereaux M.D., Ph.D., of McMaster University, and colleagues reported online in The Lancet.The investigators in the POISE (PeriOperative Ischemic Evaluation) trial said that their findings suggest the need to reconsider guidelines that currently recommend beta-blocker therapy for patients undergoing non-cardiac surgery.
Among patients with coronary artery disease, beta blockers are considered a cornerstone treatment that can improve survival in patients with angina, MI, peripheral arterial disease and heart failure, according to Lee A. Fleisher, M.D., of the University of Pennsylvania and Don Poldermans, M.D., Ph.D., of Erasmus Medical Center, Rotterdam, Holland.
In a commentary published with the POISE results, Drs. Fleisher and Poldermans suggested a reason for the troubling results could be the regimen -- 100 mg two to four hours before surgery followed by 100 mg within six hours after surgery, which meant that on the day of surgery a patient could have received as much as 200 mg of metoprolol, which is half of the maximum therapeutic dose.
By contrast, they wrote, in clinical practice the typical starting dose for heart failure patients is 12.5 mg to 25 mg and for hypertension the initial dose is usually 25 mg to 100 mg.
The trial randomized 8,351 surgery patients who had or were at risk for atherosclerosis to extended release metoprolol succinate or placebo. The mean age of patients was 69 and just over a third were women.
Patients were enrolled from October 2002 through July 2007 at 190 hospitals in 23 countries. Forty-two percent underwent vascular surgery, roughly 22% had intraperitoneal surgery, and about 21% had orthopedic surgery. Almost of half of the patients (47%) had general anesthesia.
The study drug was administered two to four hours before non-cardiac surgery, within six hours after surgery, and for 30 days thereafter. The primary endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest.
Patients who received metoprolol were less likely than those given placebo to reach the primary endpoint (5.6% versus 6.9%, P=0.0399) and were also significantly less likely to have an MI (4.2% versus 5.7% P=0.0017).
Likewise, fewer metoprolol patients required revascularization (0.3% versus 0.6% P=0.00123) and they also were less likely to develop clinically significant atrial fibrillation (P=0.0435).
But mortality and stroke rates were significantly worse in the beta-blocker groups, with 129 deaths compared with 97 in the placebo group (P=0.0317), and 41 strokes versus 19 in the placebo arm (P=0.0053).
Moreover, most of the stroke patients "were left requiring help to do everyday activities or were incapacitated," the researchers wrote. By contrast, very few of the non-fatal MI patients developed congestive heart failure or were incapacitated at hospital discharge.
There were also significantly more cases of clinically significant hypotension (625 cases versus 404 P <0.0001) href="http://www.thelancet.com/journals/lancet/article/PIIS0140673608606017/abstract?isEOP=true" target="_blank">
By Peggy Peck
HAMILTON, Ontario, 14 may 2008-- High-dose extended release metoprolol (Toprol XL) just before, shortly after, and for a month following non-cardiac surgery increased the risk of stroke and death within 30 days, researchers here reported.But the beta-blocker therapy reduced the number of non-fatal heart attacks and cardiac arrests, Philip J. Devereaux M.D., Ph.D., of McMaster University, and colleagues reported online in The Lancet.The investigators in the POISE (PeriOperative Ischemic Evaluation) trial said that their findings suggest the need to reconsider guidelines that currently recommend beta-blocker therapy for patients undergoing non-cardiac surgery.
Among patients with coronary artery disease, beta blockers are considered a cornerstone treatment that can improve survival in patients with angina, MI, peripheral arterial disease and heart failure, according to Lee A. Fleisher, M.D., of the University of Pennsylvania and Don Poldermans, M.D., Ph.D., of Erasmus Medical Center, Rotterdam, Holland.
In a commentary published with the POISE results, Drs. Fleisher and Poldermans suggested a reason for the troubling results could be the regimen -- 100 mg two to four hours before surgery followed by 100 mg within six hours after surgery, which meant that on the day of surgery a patient could have received as much as 200 mg of metoprolol, which is half of the maximum therapeutic dose.
By contrast, they wrote, in clinical practice the typical starting dose for heart failure patients is 12.5 mg to 25 mg and for hypertension the initial dose is usually 25 mg to 100 mg.
The trial randomized 8,351 surgery patients who had or were at risk for atherosclerosis to extended release metoprolol succinate or placebo. The mean age of patients was 69 and just over a third were women.
Patients were enrolled from October 2002 through July 2007 at 190 hospitals in 23 countries. Forty-two percent underwent vascular surgery, roughly 22% had intraperitoneal surgery, and about 21% had orthopedic surgery. Almost of half of the patients (47%) had general anesthesia.
The study drug was administered two to four hours before non-cardiac surgery, within six hours after surgery, and for 30 days thereafter. The primary endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest.
Patients who received metoprolol were less likely than those given placebo to reach the primary endpoint (5.6% versus 6.9%, P=0.0399) and were also significantly less likely to have an MI (4.2% versus 5.7% P=0.0017).
Likewise, fewer metoprolol patients required revascularization (0.3% versus 0.6% P=0.00123) and they also were less likely to develop clinically significant atrial fibrillation (P=0.0435).
But mortality and stroke rates were significantly worse in the beta-blocker groups, with 129 deaths compared with 97 in the placebo group (P=0.0317), and 41 strokes versus 19 in the placebo arm (P=0.0053).
Moreover, most of the stroke patients "were left requiring help to do everyday activities or were incapacitated," the researchers wrote. By contrast, very few of the non-fatal MI patients developed congestive heart failure or were incapacitated at hospital discharge.
There were also significantly more cases of clinically significant hypotension (625 cases versus 404 P <0.0001) href="http://www.thelancet.com/journals/lancet/article/PIIS0140673608606017/abstract?isEOP=true" target="_blank">
No comments:
Post a Comment