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Aspirin, clopidogrel or ticlopidine for stroke prevention?

 

Clinical bottom line

Clopidogrel and ticlopidine prevent a few more vascular events than aspirin (NNT 92), at a cost of somewhat more adverse events. The cost per event prevented is very high.


Reference

GJ Hankey et al. Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials. Stroke 2000 31: 1779-1784.

Systematic review

Randomised trials comparing clopidogrel or ticlopidine with aspirin in patients at high risk of vascular disease (ischaemic of the cerebral, coronary or peripheral circulation) were sought. There had to be at least one month follow up. Several databases were searched, including a specialised Cochrane database and that of the antithrombotic trialists collaboration.

Vascular events, defined as stroke, myocardial infarction, or death were the outcomes sought. Adverse events, like intracranial haemorrhage, gastrointestinal haemorrhage, and others serious events, were also sought.

Results

Four trials (three with ticlopidine) were found, with 12 to 40 months of follow up. Two (CAPRIE and TASS) were large, with several thousand patients, and two had fewer than 350 patients. In total there were 22,656 patients. The average age was about 63 years, about two thirds were men, and most were white.

There was little difference in vascular events between treatments (Figure 1), though there was a statistically significant benefit with thienopyridines, with a relative risk of 0.92 (0.86 to 0.98). The number needed to treat for about two years with thiopyridine to prevent one more vascular event than with aspirin was 92 (52 to 458). This amounts to prevention or delay of about 11 vascular events for every 1,000 patients treated with a thienopyridine.

Figure 1: Thiopyridines (clopidrogel red, ticlopidine yellow) and aspirin compared


The event rates for individual outcomes are shown in Table 1, with statistically significant results with a cyan background.

Table 1: Individual vascular endpoints

Event

Thienopyridine (%)

Aspirin (%)

Stroke (all)

5.7

6.4

Ischaemic/unknown stroke

5.5

6.1

Myocardial infarction

3.4

3.9

Vascular/unknown death

4.5

4.8

All cause mortality

6.5

6.8

The rates of adverse events are shown in Table 2. Statistically significant results where thienopyridines are better have a cyan background, while those where aspirin is better have a blue background.

Table 2: Adverse events

Event

Thienopyridine (%)

Aspirin (%)

Intracranial haemorrhage

0.3

0.4

Extracranial haemorrhage

8.6

8.9

Gastrointestinal haemorrhage

1.8

2.6

Indigestion/nausea/vomiting

14.8

17.1

Diarrhoea clopidogrel

4.5

3.4

Diarrhoea ticlopidine

20.4

9.9

Skin rash clopidogrel

6.0

4.6

Skin rash ticlopidine

11.8

5.5

Neutropenia clopidogrel

0.1

0.2

Neutropenia ticlopidine

2.3

0.8

Thrombocytopenia clopidogrel

0.3

0.3

Comment

Clearly there are benefits and harms associated with each strategy, and confidence intervals were wide. The implications for costs are significant. Treating 1000 patients with clopidogrel rather than aspirin could prevent as many as 19 vascular events at a cost of £57,000 ($85,000) per event prevented, or as few as two events at a cost of £533,000 ($800.000) per event prevented.