Warfarin, Aspirin or Both after Myocardial Infarction (2002)

Design: Multicenter, open-label RCT

 P  < 75 yo, hospitalized for AMI (i.e. SECONDARY prevention)

Excluded: indication or CI for study drugs, malignancy, poor compliance

Mean duration of observation: 4 years

  • Warfarin (target INR 2.8-4.2)
  • ASA 75mg daily + Warfarin (target INR 2-2.5)
  •  ASA 160mg daily
 O Primary outcome: composite of death, non-fatal reinfarction, or thromboembolic cerebral stroke

  • Intention to treat analysis

Versus ASA alone

  • RR for warfarin + ASA: 29% (P = 0.001), NNT = 67
  • RR for warfarin alone: 19% (P = 0.03), NNT = 100
  • NSS in mortality (benefit with non-fatal reinfarction and TE stroke)
    • TE stroke for combination + warfarin alone ~ same (Rate ratio: 0.52)
    • Benefit for reinfarction for combination > warfarin alone
      (Rate ratio: 0.56 for combination vs. 0.74 for warfarin alone)


  • NNH for 1 major bleeding episode:
    • 250 for warfarin + ASA
    • 200 for warfarin alone

Take-away points:

  • Main benefit of warfarin + ASA or warfarin alone over ASA for secondary prevention for MI is the:
    Prevention of non-fatal reinfarction and TE stroke

    • No SS difference in mortality
  • But…comes with increased bleeding
    • Increased major bleeding with combination + warfarin > ASA
      • 4 times as many major bleeding
    • Increased minor bleeding with combination

C3.2 R4(c): Clarify a medication order with a prescriber #2

ID: TAS is a 37 yo male (wt = 134 kg) admitted with PE and DVT

  • Currently bridging from IV heparin to warfarin for PE/DVT Treatment
  • Original order was for: warfarin 10mg PO once daily x 3 days

Patient’s labs are as follows:

Aug 31 Sept 1 Sept 2
INR 1.0 1.0 1.8
Warfarin 10mg 10mg

On Sept 2, there was a 0.8 jump in INR. Based on the half-lives of clotting factors, the increase by 0.8 is likely due to the peak effect of 1st 10mg dose. Generally, when there is an increase greater than 0.5, we could consider withholding or decreasing the dose.  If the 3rd 10mg dose is administered, the INR may exceed our therapeutic range of 2-3.

Clarified with the prescriber if she would like to decrease or withhold the dose.

Order written:

  1. Please discontinue previous warfarin order.
  2. Warfarin 2mg PO x 1 dose today – MD to reassess tomorrow.

FYI: Follow up

Sept 3 Sept 4
INR 1.6 1.9 2.2
Warfarin 8mg 8mg