ASPRE Trial: A Combined Risk Algorithm and Use of Aspirin to Prevent Preterm Preeclampsia

BACKGROUND AND PURPOSE:

  • Multiple studies have demonstrated beneficial effects of low dose aspirin for prevention of preeclampsia
  • ACOG supports the key USPSTF findings and recommends considering the use of low dose aspirin (81 mg/day) between 12 and 28 weeks’ gestation in women with known clinical risk factors including
    • History of preeclampsia, especially if accompanied by an adverse outcome
    • Multifetal gestation
    • Chronic hypertension
    • Diabetes (Type 1 or Type 2)
    • Renal disease
    • Autoimmune disease (for example, systematic lupus erythematosus, antiphospholipid syndrome)
  • An alternative Bayesian risk algorithm that combines multiple clinical, biochemical and fetal sonographic (functional) findings at 11 to 13 weeks has been well studied an appears to have superior performance characteristics when compared to clinical factors alone
    • Applicable to general pregnant population, not just high risk
  • Previous studies have found that (1) starting aspirin ≤ 16 weeks provides greater preventative benefit; (2) prevention is limited to preterm preeclampsia; (3) there is a positive dose-dependent benefit effect beyond 81 mg/day; (4) taking aspirin in the evening may be beneficial
  • Purpose: The goal of the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial (Rolnik, NEJM 2017) was to determine if 150 mg of aspirin at night could reduce the incidence of preterm preeclampsia in women identified at high risk using the combined Bayesian model approach

METHODS:

Randomized, double-blind, placebo-controlled trial (RCT)

  • Population: Women undergoing their routine prenatal visit at 11 weeks 0 days through 13 weeks 6 days
  • Screening tool: Bayesian risk algorithm which assesses the following factors
    • Age
    • Weight and height (BMI)
    • Racial/ethnic origin (white, Afro-Caribbean, South Asian, East Asian, and mixed)
    • Medical History
      • Chronic hypertension
      • Systemic lupus erythematosus or antiphospholipid syndrome
      • Diabetes mellitus type 1 or 2
    • Mode of conception – spontaneous vs. assisted
    • Obstetrical history
      • Parity ( ≥ 24 weeks)
      • Previous preeclampsia
      • Gestational age and weight at delivery in the last pregnancy
      • Interval since last pregnancy
    • Family history of preeclampsia in the patient’s mother
    • Biomarkers
      • Mean arterial pressure (MAP)
      • Uterine artery pulsatility index (UtA-PI)
      • Pregnancy associated plasma protein-A (PAPP-A)
      • Placental growth factor (PlGF)
  • Intervention:  150 mg dose/day of aspirin or placebo from 11 to 14 weeks until 36 weeks
    • 2971 women out of 26,941 women (11.0%) were ‘screen positive’ for risk of preterm preeclampsia
    • Following exclusion, withdrawal and loss to follow up, 798 participants remained in the aspirin group and 822 in the placebo group

RESULTS:

Delivery with preeclampsia < 37 weeks:  Definition of preeclampsia based on International Society for the Study of Hypertension in Pregnancy criteria

  • 1.6% in the aspirin group had preterm preeclampsia vs. 4.3% in the placebo group (odds ratio 0.38; 95% CI 0.20 to 0.74; P=0.004)

Secondary Outcomes:  Such as abruption, stillbirth, miscarriage, neonatal morbidity and mortality

  • No statistical differences found but study not powered to draw definitive conclusions

Adverse Events: Including maternal, fetal and neonatal

  • No statistical differences between groups overall, including anemia, vaginal, nasal and other bleeding

CONCLUSION:

  • Aspirin did not reduce the incidence of term preeclampsia
  • In singleton pregnancies, using a combined Bayesian risk assessment tool, 150 mg of aspirin nightly from 11-14 weeks until 36 weeks led to a 62% reduction in the rate of preterm preeclampsia compared to placebo

Learn More – Primary Sources:

Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

Competing risks model in screening for preeclampsia by maternal characteristics and medical history

Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation