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DEPARTMENT OF ANESTHESIA AND
PERIOPERATIVE CARE Anesthesiology Service (129)
4150
Clement Street
Date: November 11, 2007
The POISE
trial results have been reported in abstract form by Dr. P.J. Devereaux at the American Heart Association Annual Scientific
Session,
The results
are mixed.
The primary endpoint of CV death, MI or cardiac arrest was reduced in the metoprolol group compared with placebo (5.8% vs. 6.9%, hazard ratio [HR] 0.83, 95% CI 0.70-0.99, p = 0.04), driven by a reduction in non-fatal MI (3.6% vs. 5.1%, HR 0.70, p = 0.0007). There were also reductions with metoprolol in revascularization (0.3% vs. 0.6%, p = 0.01), atrial fibrillation (2.2% vs. 2.9%, p = 0.04). However, total mortality was increased in the metoprolol group (3.1% vs. 2.3%, HR 1.33, p = 0.03) as was stroke (1.0% vs. 0.5%, HR 2.17, p = 0.005). The metoprolol group also had increased rates of significant hypotension (15.0% vs. 9.7%, p < 0.0001) and significant bradycardia (6.6% vs. 2.4%, p < 0.0001).
Dr. Devereaux concludes: Among patients undergoing noncardiac surgery, treatment with the beta-blocker metoprolol was associated with a reduction in the primary
endpoint of CV death, MI or stroke at 30 days compared with placebo,
but total mortality was higher in the metoprolol group.
Dr. Devereaux concludes that routine prophylactic
therapy does not appear to be a safe approach to reducing CV events in this
population.
The POISE
study is a very large prospective randomized clinical trial. The methods
and results of the trial need to be very carefully reviewed and taken
very seriously. There are major differences between the inclusion criteria
and dosing of metoprolol used in the POISE trial and those used in the
perioperative beta blocker protocol (PCRRT) developed at the
From the
Physician’s Desk Reference: For hypertension, the usual initial dosage
of Metoprolol XL is 25 to 100 mg daily in a single dose. The
dosage may be increased in weekly intervals. For angina, the dosage
should be individualized but the usual initial dosage is 100 mg
The initial
dose of metoprolol XL in the POISE trial
is 2 to 8 times the recommended initial dosage from the physician’s
desk reference. The POISE starting dosage of Metoprolol XL
is 8 times the recommended dose in the PCRRT protocol. In the Poldermans study
(NEJM 24:341 1999), the starting dose of bisoprolol was
5 mg PO QD. Bisoprolol 5 mg PO QD is similar
to Atenolol 25 mg PO QD or Metoprolol XL
25 mg PO QD. The POISE starting dose was 8 times the initial dosage
used in the Poldermans study.
The results
of the POISE study need to be very carefully understood prior to
making decisions about perioperative beta blockade. It is clear from
the POISE
study that perioperative beta blockers can have significant risk
if used incorrectly. It is very important that protocols for perioperative
beta blockade be extensively tested prior to implementation. The
PCRRT
protocol from the
Sincerely
Arthur Wallace, M.D., Ph.D. Phone: 415-750-2069
VAMC
Anesthesiology (129) Pager: 415-210-6077
4150 Clement St.
Fax: 415-750-6946