Grand Rounds

What is the Optimal Dosage of Aspirin to Prevent Preeclampsia?

BACKGROUND AND PURPOSE:

There is good evidence that aspirin prevents preeclampsia in women at risk, but there is no agreement on the actual dose
In the US, tablets are only available in 81mg and 325mg tablets, while the ASPRE study used 150mg dose
Seidler et al. (AJOG 2018) evaluated optimal aspirin dosing for preeclampsia prevention

Individual participant data (IPD) from a large meta-analyses of preeclampsia prevention was analyzed and compared to ASPRE findings
Exposures
- ≤81 mg
- >81 mg
- Placebo
Primary outcomes
- Preeclampsia
- Preeclampsia with PTB <37 weeks gestation

22 previous RCTs, totaling 30,532 women were included
Preeclampsia was reduced with aspirin dose ≤ 81 mg relative to placebo
- Pooled relative risk (RR) 0.92; 95% CI 0.85 – 0.99
Greater risk reduction was seen at doses of >81 mg relative to placebo
- Pooled RR, 0.74; 95% CI, 0.60 – 0.92
- Similar to results from the ASPRE trial (RR 0.72)
For preeclampsia with PTB, a similar pattern was seen
- 81 mg: IPD pooled RR, 0.86; 95% CI, 0.75-0.98
- >81 mg: IPD pooled RR, 0.75; 95% CI 0.54-1.04
- Less effect than seen in ASPRE trial (RR, 0.38)
Adjusting for confounding variables did not alter results
Among the pooled RCTs, preeclampsia and preeclampsia with PTB declined with increasing aspirin doses, but with overlapping confidence intervals
In pooled RCTs that used IPD, the lowest predicted rate of preeclampsia with PTB (1.6%) was observed at a daily dose of 100 mg, the same rate as in the ASPRE trial (1.6%)

There is a dose-response effect of aspirin on prevention of preeclampsia and preeclampsia with PTB up to 150 mg daily
The authors suggest that a future RCT to compare higher doses such as 150 mg or 162 (double the 81mg tablet) vs 81 mg dose is required and “could benefit millions of pregnant women and their fetuses worldwide at a very low cost and risk”

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