Is Aspirin for Early Preeclampsia Prophylaxis Cost-Effective?

BACKGROUND AND PURPOSE:

• Current practice in Canada and US is to screen for preeclampsia based on clinical risk factors
  • Women at high risk are offered low-dose aspirin (75-162 mg/day in Canada; US recommendations 81 mg/day)
• Ortved et al. (Ultrasound in Obstetrics & Gynecology, 2018) sought to determine whether using the ASPRE risk assessment approach with low-dose aspirin for prevention of early onset preeclampsia is cost effective

METHODS:

• Decision tree analysis
  • Theoretical population based on 387,516 live births in Canada (over 1 year period)
  • Clinical and financial impact were simulated and modelled
• Analysis based on
  • Fetal Medicine Foundation algorithm for prediction of early onset preeclampsia (see ‘Related ObG Topics’ below) in first trimester
    • Clinical factors, biomarkers and ultrasound
  • Aspirin started in high risk pregnancies <16 weeks
• The probabilities and costs based on published literature and public databases

RESULTS:

• Theoretical population of 387,516 births per year
  • Screening and aspirin use: 705 cases of early preeclampsia
  • Current practice: 1801 cases
• Estimated total cost (Canadian dollars)
  • Screening and aspirin use: $9.52 million
  • Current practice: $23.91 million
• Annual cost saving to the Canadian healthcare system of approximately $14.39 million

CONCLUSION:

• Screening using clinical factors/biomarkers and ultrasound with aspirin prophylaxis for those at high risk to reduce early preeclampsia was found to be cost effective

Learn More – Primary Sources: 

Cost-effectiveness of first-trimester screening with early preventative use of aspirin in women at high risk of early-onset pre-eclampsia 

Aspirin Treatment for Women at Risk for Preeclampsia – ACOG, SMFM and USPSTF Recommendations

FINDINGS:

ACOG/SMFM have released guidance aligned with USPSTF regarding the use of low-dose aspirin during pregnancy to prevent preeclampsia.  When indicated, low-dose aspirin should be started between 12 to 28 weeks and continued until delivery.  Optimally, aspirin usage should begin <16 weeks.

Recommended (high risk)

• Offer low-dose aspirin (81 mg/day) to women with ≥1 high risk factors
  • 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)

Moderate Risk Factors

• Offer low-dose aspirin (81 mg/day) to women with ≥2 moderate risk factors
  • Nulliparity
  • Obesity (BMI >30)
  • Personal history
    • Low birthweight or SGA
    • Previous adverse pregnancy outcome
    • >10-year pregnancy interval
  • Family history of preeclampsia
    • Sister or mother
  • Social and demographic characteristics
    • Black race (as a proxy for underlying racism)
    • Lower income
    • Maternal age ≥35 years
  • IVF

Note: USPSTF does allow for consideration of aspirin prophylaxis if ≥1 moderate risk factor is present and states “Clinicians should use clinical judgment in assessing the risk for preeclampsia and discuss the benefits and harms of low-dose aspirin use with their patients”

Universal Implementation

• Evidence supports a risk-based approach
• ACOG/SMFM acknowledges that in some settings, a majority of patients will fall in to either high or moderate risk categories, and therefore

In these instances, universal implementation (eg, offering low-dose aspirin to all patients within such practices or institutions) may be medically reasonable

Not Recommended Without Preeclampsia Risk Factors

• Low risk: Previous uncomplicated full-term delivery
• Insufficient Evidence
  • Prior unexplained stillbirth (insufficient evidence)
  • Prevention of fetal growth restriction
  • Prevention of spontaneous PTB
• No Benefit
  • Prevention of early pregnancy loss

USPSTF Guidance

• The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia as per categories above (B recommendation – offer or provide this service)

Benefits

• The most recent systematic evidence review (see ‘Learn More – Primary Sources) provided more precise estimate of the association between aspirin and the prevention of perinatal mortality (4% to 44% reduction in fetal and neonatal deaths)
• Otherwise, benefits of low-dose aspirin for women at risk for preeclampsia were similar to previous reviews with lower risks for the following (moderate certainty)
  • Preeclampsia: Pooled relative risk (RR) 0.85 (95% CI, 0.75-0.95)
  • Perinatal mortality: Pooled RR 0.79 (95% CI, 0.66-0.96)
  • Preterm birth: Pooled RR 0.80 (95% CI, 0.67-0.95)
  • Intrauterine growth restriction: Pooled RR 0.82 (95% CI, 0.68-0.99)

Harms

• No significant association was found for
  • PPH or other bleeding-related harms
  • Rare perinatal or longer-term harms
• Long-term child developmental outcomes in offspring from in utero exposure to low-dose aspirin
  • Follow-up data from the Collaborative Low-dose Aspirin Study in Pregnancy (CLASP), found no differences in physical or developmental outcomes at 12 to 18 months

KEY POINTS:

• Risk factors used for ACOG/SMFM recommendations only include factors obtained from the medical record
  • Uterine artery Doppler ultrasonography and biochemical markers are not included
  • ACOG/SMFM acknowledge that other studies, in particular the ASPRE trial (see ‘Related ObG Topics’ below), have incorporated ultrasound and maternal serum markers as well as doses >81 mg, but state

Further, the screening algorithm used includes first-trimester serum markers, including placental growth factor and pregnancy-associated plasma protein-A, as well as uterine artery dopplers, which limits the generalizability to a U.S. population. Therefore, a higher dose or doubling of the available 81-mg dose cannot be recommended at this time.

Screening for Preeclampsia

• USPSTF
  • Recommends that blood pressure measurements should be obtained during each prenatal care visit throughout pregnancy
  • Does not find evidence to support routine use of point-of-care urine protein tests for preeclampsia screening
• Various studies have incorporated not only clinical risk factors but also biochemical markers and ultrasound to determine which women are at risk for early onset preeclampsia and may benefit from aspirin prevention (see ‘Related ObG Topics’)
• ACOG/SMFM considers the supporting data for the use of such combined risk assessment algorithms to be limited and without more prospective clinical utility trials, states that

…biomarkers and ultrasonography cannot accurately predict preeclampsia and should remain investigational.

Learn More – Primary Sources:

ACOG Practice Advisory: Low-Dose Aspirin Use for the Prevention of Preeclampsia and Related Morbidity and Mortality

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia 

USPSTF: Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality

USPSTF: Screening for Hypertensive Disorders of Pregnancy

USPSTF: Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

ACOG/SMFM Committee Opinion 743: Low-Dose Aspirin Use During Pregnancy

SMFM: Prophylactic low-dose aspirin for preeclampsia prevention—quality metric and opportunities for quality improvement