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Warfarin or aspirin or both after myocardial infarction

 

Clinical bottom line

Warfarin plus aspirin is better than aspirin alone after a heart attack. Over four years, treating 1,000 patients with warfarin plus aspirin would have prevented about 50 events, mainly reinfarctions, but would have caused about 20 major bleeds. The question is whether the benefits are worth the hassle.


Reference


M Hurlein et al. Warfarin, aspirin, or both after myocardial infarction. New England Journal of Medicine 2002 347: 969-974.


Study

This study was properly randomised with concealed allocation, but open. Men and women younger than 75 years (and without malignant disease, or contraindication to aspirin or warfarin) who had survived an acute myocardial infarction were randomly assigned to one of three treatments:

The main outcome was a composite of death, nonfatal myocardial infarction, or stroke. The size and duration was predicated on the number of events that occurred.

Results

The study had 3,630 patients. The mean initial age was about 60 years, about three quarters were men and about half smoked. The mean duration of observation was 1,445 days (3.96 years). Only 14 patients were lost to follow up. The mean INR was 2.8 in patients receiving warfarin alone and 2.2 in those on warfarin and aspirin.

There were 625 events, mostly deaths and reinfarctions. There was a lower rate of events with warfarin plus aspirin than for aspirin alone (relative rate 0.8, 95% CI 0.6 to 0.9), but not significantly lower than for warfarin alone (0.8, 95% CI 0.7 to 0.99). Figure 1 shows the overall number events per 100 patient years, and Table 1 the actual events. The number needed to treat with aspirin plus warfarin rather than aspirin alone for four years to prevent one death, reinfarction or stroke was 20 (12 to 51). For warfarin compared with aspirin it was 30 (16 to 478).

Figure 1: Percentage of composite events with each intervention


Table 1: Events in each treatment group

Event

Aspirin

Warfarin

Aspirin + warfarin

Number of patients

1206

1216

1208

Reinfarction

117

90

69

Thromboembolic stroke

32

17

17

Death

92

96

95

Total withdrawals

191

387

480

Patient unwilling to continue

3

42

63

Bleeding

20

60

89

Major bleeds

8

33

28

Many more people were withdrawn from treatment with warfarin (with or without aspirin) than with aspirin alone (Table 1). This included patients unwilling to continue, and because of bleeding. Major bleeds were more frequent when warfarin was part of the treatment. For both warfarin treatments the relative risk was about 4, and the number needed to treat with warfarin plus aspirin for four years to have one more major bleed than with aspirin was 60 (38 to 144) and with warfarin alone was 49 (33 to 97).

Comment

Adding warfarin to aspirin reduced the composite endpoint of deaths, reinfarction or stroke compared with aspirin alone after a heart attack. Over four years, treating 1,000 patients with warfarin plus aspirin would have prevented about 50 events, mainly reinfarctions, but would have caused about 20 major bleeds. Withdrawals with warfarin were far higher than with aspirin.

The issue here is not whether warfarin is more beneficial than aspirin. It is, and the combination even more so. The question is whether it is worth bothering, given the hassle that is warfarin treatment. For some patients it may be. Others would deem it intrusive.