Myocardial infarction: no clear benefit from adding fixed-dose warfarin to aspirin.

Clinical bottom line (level 1b)

  1. Patients with a myocardial infarction who received 1 mg warfarin and 80 mg aspirin compared with 160 mg aspirin were more likely to have a non-fatal myocardial infarction (NNH = 48 at 30 months) or ischaemic stroke (NNH = 130 at 30 months) .
  2. There was no clear effect on mortality or major haemorrhage.
  3. Patients given 3 mg warfarin and 80 mg aspirin compared with 160 mg aspirin were not clearly less likely to die, have a non-fatal myocardial infarction or an ischaemic stroke.
Coumadin Aspirin Reinfarction Study (CARS) Investigators : Lancet 1997; 350: 389-396
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 293 acute hospitals, USA and Canada

8803 patients (aged 21 to 85 (82% < 70), 77% male) with a myocardial infarction (raised cardiac enzymes with typical chest pain for at least 15 minutes or typical ECG changes)

Excluded if
  • acute pericarditis
  • uncontrolled hypertension
  • known hypersensitivity to warfarin derivatives
  • liver disease or renal disease
  • anaemia, thrombocytopaenia, haematuria
  • abnormal thyroid function tests
  • congestive heart failure (Killip class III or IV)
  • circulatory shock
  • rest angina unresponsive to medical therapy
  • serious ventricular arrhythmias within 24 hours of randomisation
  • history of bleeding, stroke without full recovery or previous intracranial or subarachnoid haemorrhage
  • co-existing illness with expected survival of < 4 years
  • < 3 days or > 21 days after myocardial infarction
  • women with child-bearing potential
Control Group: (n = 3393, 3393 analysed): aspirin 160 mg daily
Experimental Group: (n = 2028, 2028 analysed): aspirin 80 mg daily and warfarin 1 mg daily
Experimental Group: (n = 3382, 3382 analysed): aspirin 80 mg daily and warfarin 3 mg daily
Drugs that interacted with warfarin were prohibited.
100% followed for 30 months
Outcome notes:
  • any major haemorrhage : intracranial haemorrhage; bleeding requiring surgical intervention, transfusion or contributed to death; fall in haemoglobin 2 g/dl or more

The evidence

1 mg warfarin and 80 mg aspirin v. 160 mg aspirin
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
non-fatal MI 30 months 230
(6.78%)		 180
(8.88%)		 -31%
(-58% to -9%)		 -2.10%
(-3.60% to -0.60%)		 -48
(-170 to -28)
ischaemic stroke 30 months 21
(0.62%)		 28
(1.38%)		 -123%
(-292% to -27%)		 -0.76%
(-1.33% to -0.19%)		 -130
(-530 to -75)
death 30 months 102
(3.01%)		 63
(3.11%)		 -3%
(-41% to 24%)		 -0.10%
(-1.05% to 0.85%)		 -1000
(NNT = 95 to infinity;
NNH = 120 to infinity)
any major haemorrhage 30 months 57
(1.68%)		 42
(2.07%)		 -23%
(-83% to 17%)		 -0.39%
(-1.15% to 0.36%)		 -260
(NNT = 87 to infinity;
NNH = 270 to infinity)

3 mg warfarin and 80 mg aspirin v. 160 mg aspirin
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
non-fatal MI 30 months 230
(6.78%)		 210
(6.21%)		 8%
(-10% to 24%)		 0.57%
(-0.60% to 1.74%)		 180
(NNT = 170 to infinity;
NNH = 57 to infinity)
ischaemic stroke 30 months 21
(0.62%)		 31
(0.92%)		 -48%
(-157% to 15%)		 -0.30%
(-0.71% to 0.12%)		 -340
(NNT = 140 to infinity;
NNH = 850 to infinity)
death 30 months 102
(3.01%)		 118
(3.49%)		 -16%
(-51% to 11%)		 -0.48%
(-1.33% to 0.36%)		 -210
(NNT = 75 to infinity;
NNH = 280 to infinity)
any major haemorrhage 30 months 57
(1.68%)		 75
(2.22%)		 -32%
(-86% to 6%)		 -0.54%
(-1.20% to 0.12%)		 -190
(NNT = 84 to infinity;
NNH = 830 to infinity)

Citation

  1. Coumadin Aspirin Reinfarction Study (CARS) Investigators , : Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet 1997; 350: 389-396
Search Terms: myocardial near infarction in Cochrane
Contributor: Chris Ball and Clare Wotton, February 2000
Reviewer:

Clinical Question.
Patient myocardial infarction
Intervention or Exposure warfarin and aspirin
Outcome reinfarction