Effect of perioperative β blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

The article by Juul et al (1) showing that perioperative metoprolol
succinate CR/ XL did not significantly affect mortality and cardiac
morbidity in patients with diabetes undergoing non-cardiac surgery is in
contrast with the current guidelines and some previously reported studies
demonstrating efficacy of perioperative beta-blockade (2-5). There is a
potential explanation for the contrasting results.

In the DIPOM study metoprolol was started as a test dose of 50 mg the
evening before surgery and only continued until discharge or a maximum of
8 days. However, the primary combined outcome measure was evaluated until
18 months follow up. Based on the Kaplan-Meier curves shown in figure 2 of
the article it appears that the curves did indeed show a lower event rate
in the metoprolol group during the period the patients were receiving
active medication. However, subsequently the event rates increased in the
metoprolol group, which is not surprising given that beta-blockade was
withdrawn upon discharge or at the end of 8 days and during follow up only
7 patients in the metoprolol group and 5 in the placebo group were taking
any beta blockers. The abrupt increase in events could have occurred due
to aggravation of cardiovascular events secondary to beta-blocker
withdrawal and/ or lack of protection afforded by beta blocker therapy
during active therapy. These results are in clear contrast to those
reported by Poldermans et al (2) who demonstrated that when beta blocker
therapy was given appropriately (started >=7 days before surgery and
continued for 30 days post-operatively) it reduced the perioperative
incidence of cardiac death and non-fatal MI at 30 days in patients
undergoing vascular surgery. If the primary objective of DIPOM study (1)
was to examine the event rates during the extended follow up, the active
treatment should have been continued accordingly.

1. Juul AB, et al. Effect of perioperative beta blockade in patients
with diabetes undergoing major non-cardiac surgery: randomised placebo
controlled, blinded multicentre trial. BMJ. 2006;332(7556):1482-1485.

2. Eagle KA, et al. American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Committee to Update the
1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac
Surgery). ACC/AHA guideline update for perioperative cardiovascular
evaluation for noncardiac surgery---executive summary a report of the
American College of Cardiology/American Heart Association Task Force on
Practice Guidelines (Committee to Update the 1996 Guidelines on
Perioperative Cardiovascular Evaluation for Noncardiac Surgery).
Circulation. 2002;105(10):1257-1267.

3. Poldermans D, et al. The effect of bisoprolol on perioperative
mortality and myocardial infarction in high-risk patients undergoing
vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying
Stress Echocardiography Study Group. N Engl J Med. 1999;341(24):1789-1794.

4. Raby KE, et al. The effect of heart rate control on myocardial
ischemia among high-risk patients after vascular surgery.Anesth Analg.
1999;88(3):477-482.

5. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin
EM. Perioperative beta-blocker therapy and mortality after major
noncardiac surgery. N Engl J Med. 2005;353(4):349-361.

Competing interests:
None declared