Low-molecular-weight heparin and aspirin in the prevention of recurrent early-onset pre-eclampsia in women with antiphospholipid antibodies: the FRUIT-RCT.

OBJECTIVE

To examine whether combined treatment with low-molecular-weight heparin (LMWH) and aspirin reduces recurrent hypertensive disorders of pregnancy (HD: pre-eclampsia, eclampsia or HELLP syndrome) in women with antiphospholipid antibodies (aPLA) and a previous delivery for HD and/or small-for-gestational-age (SGA) birthweight before 34 weeks gestation.

STUDY

DESIGN

This multicentre randomised controlled trial was performed between December 2000 and December 2009. Women were recruited from all eight university and six non-university/teaching hospitals in The Netherlands, two university hospitals in Australia and one university hospital in Sweden. Thirty two women with a previous delivery <34 weeks gestation with HD and/or SGA and aPLA were included before 12 weeks gestation. The intervention was daily LMWH with aspirin or aspirin alone.

PRIMARY OUTCOMES: recurrent HD onset <34 weeks and recurrent HD irrespective of gestational age. Analysis by intention-to-treat.

RESULTS

After an interim analysis, recruitment was ceased: accrual was low and the incidence of recurrent HD was far lower (3%) than expected (60%). The final analysis, performed on 32 women, shows no difference in the primary outcomes (LMWH and aspirin 0/16 versus aspirin only 1/16, risk difference 6.25% [CI -17 to 27%] for recurrent HD onset <34 weeks and 0/16 for LMWH and aspirin versus 2/16 for aspirin only, risk difference 12.5% [CI -15 to 35%] for HD irrespective of gestational age).

CONCLUSION

In this population of women with aPLA, who had previously had an early delivery for HD and/or SGA prior to 34 weeks gestation, combined LMWH and aspirin treatment started before 12 weeks gestation in a subsequent pregnancy did not show reduction of onset of recurrent HD either <34 weeks gestation or irrespective of gestational age, compared with aspirin alone.