Transcript COMMIT Metoprolol LBCT Comments - ACC

Perspective on
COMMIT/CCS-2 Trial of
Metoprolol in STEMI
Christopher Cannon, M.D.
Brigham and Women’s Hospital
Boston, MA
First impression
• Wow !?
• I had predicted dramatic benefit with
multiple 0’s in the P value
Older B-blocker trials (up to 1986)
• >27,000 patients from 28 trials
• Meta-analysis:
– B-blocker (3.7%)
– Control (4.3%)
– 16% relative risk reduction
– 95% CI: 1-30%
– P=0.02
• On re-looking:
– Lower risk patients studied
– Wide confidence intervals on mortality benefit
Evolution of use of B-Blockers in AMI
• Benefits seen in meta-analysis of RCTs:
reduced mortality, re-MI, VF, rec. ischemia
• Initially contraindicated if CHF
• Then, trials in outpatients with LV dysfunction,
(with slow up-titration of dose over 3-6 mos)
B-blockers shown to reduce mortality
• The overlap: in AMI, CHF no longer seen as a
contraindication to use of B blockers
Looking at the data in COMMIT/CCS-2
• Benefit
– Reduction in re-MI
– Reduction in VF
• Risk
– Increased development of cardiogenic shock
• Biologically plausible – a negative inotropic
agent
• Increased risk of shock in first 24-48 hours
• Subgroup analysis: Shock developed in
Patients with Killip III, tachycardia, or
hypotension
Current ACC/AHA guideline on the use
of early -blocker in acute MI
(ACC/AHA Task Force Report. J Am Coll Cardiol 2004;44:671-719
•Class I: Oral -blocker therapy should be
administered promptly to those patients without a
contraindication, irrespective of concomitant
fibrinolytic therapy or performance of primary PCI.
(Level of evidence: A)
•Class IIa: It is reasonable to administer iv blocker promptly to STEMI patients without
contraindications, especially if a tachyarrhythmia
or hypertension is present. (Level of evidence: B)
Current ESC Guideline for the use
of early -blocker in acute MI
(ESC Task Force Report. Euro Heart J 2003;24:28-66
……the use of iv -blockade in the acute
phase of infarction in many countries is
extremely low. There is a good case for the
greater use of an iv -blocker when there is
tachycardia (in the absence of heart failure),
relative hypertension, or pain unresponsive to
opioids. It may be prudent to test the patient’s
response to this form of therapy by first using
a short-acting preparation. In most patients,
however, oral -blockade will suffice.
Conclusions: B-Blockade in Acute MI
• One size does not fit all
• Avoid IV B-blocker for patients with evidence
of compromised LV Function
– Start oral B blocker after 1-2 days, when stable
with lower doses, and titrate upward
• Low-medium risk patients benefit from early
IV -> oral beta-blockade
• For all medications: Need to balance benefit
and risk, for each patient
Lessons Learned from 2x2 Clinical Trials
• In 2x2 trial, if one is + and the other -, it provides a
‘negative control’ that reinforces the positive intervention
• ISIS-4/
GISSI-3
AMI
ACE inhibitor
Nitrates
+benefit
no benefit
• HOPE
GISSI-Prev.
Vasc.
Dis
ACE inhibitor
Vit E
+benefit
no benefit
• PROVE ITTIMI 22
ACS
High-dose statin
Antibiotic
+benefit
no benefit
• COMMIT/
CCS-2
AMI
Clopidogrel
Metoprotol
+benefit
+/-benefit
COMMIT/CCS-2: Major contribution
• 10 million AMI/year worldwide, ~3 million STEMI
• For metoprolol,
– We learn appropriate use for ‘well-established’ class
– New data will avoid excess risk, but allow benefit in
appropriate patients
• For clopidogrel,
– New addition for treatment for STEMI
– Improved patency, mortality and morbidity
– Could prevent 20,000 – 30,000 deaths, MI’s or
strokes per year worldwide