WARIS II

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

 I
  • Warfarin (target INR 2.8-4.2)
  • ASA 75mg daily + Warfarin (target INR 2-2.5)
 C
  •  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)

Safety:

  • 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
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2 thoughts on “WARIS II

    • Great point! Thank you! TTR was better achieved in the warfarin group but it had a wider therapeutic range than the combination. TTR was ~ 62% for warfarin alone (34% below INR of 2.8 and 4% above 4.2) but mean INR was 2.8, and TTR was ~ 47% for combined therapy group (23% below INR of 2 and 30% above 2.5).

      I always struggle on how to use the TTRs in my interpretation of the results and am trying to think this through… Since when using warfarin alone – we typically treat to a target of INR of 2-3, would it be reasonable to say that when considering it as an option in practice – the safety and efficacy results may likely be an overestimation? And that for warfarin + ASA alone, when considering a patient that hypothetically is able to stay consistently within target 2-2.5, it seems like it’d more challenging to determine whether the safety and efficacy results would be an over or under estimation since patients were ~20-30% below or above the INR. I would also guess that another thing that would help guide the interpretation of the TTR is also knowing the ranges of TTR which wasn’t reported.

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