Karin Mackay
EBM – 9/7/01
Clinical
Scenario: Patient with atypical chest pain on
presentation to ER, relieved by
nitrates. EKG showed nonspecific T wave flattening. Initial set of enzymes
normal. Second set of enzymes significant for troponin of 22. Still chest
pain
free, EKG unchanged. Heparin started. Patient will not go to cath
lab emergently.
Do we start a IIb/IIIa inhibitor?
Can
we use the PRISM-PLUS trial to answer this question?
Methods:
1915
patients randomized, study participants double-blinded to receive tirofiban,
heparin,
or tirofiban plus heparin
Entry criteria: one of the following
1. prolonged anginal pain or repetitive episodes of angina at rest or during minimal
exercise in the previous 12 hours and new transient or persistent ST-T
changes on the EKG
2. elevation of plasma levels of CK and CK-MB
Exclusion criteria: ST elevation over 20 minutes, thrombolysis in previous 48 hours,
angioplasty in the previous 6 months, bypass in the previous month, angina caused
by unidentifiable factors, platelet disorder or thrombocytopenia, active bleeding or
high risk of bleeding, CVA in the previous year, Cr > 2.5
ASA 325 mg given to all (if no contraindication)
drug infused for 48 hours
interventions postponed for 48 hours unless refractory ischemia or new MI
if interventions were done, they were encouraged to take place between 48-96 hours
while continuing the study drug
* tirofiban only group stopped prematurely secondary to a statistically significant
increase in mortality at 7 days (not seen in PRISM trial)
End Points:
primary – composite of death from all causes, new MI, or refractory ischemia within 7d
composite of above plus rehospitalization for USA at 7d, 30d, and 6 months
secondary - composite of death, new MI, refractory ischemia at 48 hours and 30d
death, new MI, refractory ischemia as separate measures
composite of death or MI
Results:
Composite end point: statistically significant decrease in events in tirofiban + heparin group
ARR NNT
7 days 5 20
30 days
3.8 26
6 months 4.4 23
New myocardial infarction:
ARR NNT
48 hours 1.6
62
7 days 3.1 32
30 days 2.6
38
Composite of MI or death:
ARR NNT
48 hours 1.7
59
7 days 3.4 29
30 days 3.2
31
Does starting the IIb/IIIa
help reduce the number of interventions?
90% in the study eventually underwent angiography
equal amount in each group needed angioplasty and bypass
those who underwent angioplasty derived a greater benefit from the tirofiban + heparin
than those who were not intervened on (this has been shown in other studies)
Problems:
tirofiban only group excluded from study
higher risk patients have a greater likelihood of ischemic complications and therefore
probably derive a greater benefit from IIb/IIIa inhibitors
no way to know if a patient will go on to intervention – since the benefits of IIb/IIIa
inhibition occur before and after intervention, cannot wait until the decision to
intervene is made to start drug
need to develop criteria to help us decide who will benefit most
question of cost effectiveness – need to be in the ICCU or CCU to get IIb/IIIa inhibitors,
drugs also expensive
some studies suggest the absolute risk of major bleeding complications is the similar to
the absolute decrease in risk of event
So what about this
patient?
given positive enzymes, patient high risk for ischemic complications
no way to know whether she will have percutaneous intervention at the time of cath
would probably benefit from IIb/IIIa inhibitor