Use of Aspirin in the Reduction of Preeclampsia in High Risk Pregnancies

Kenneth L. Smith, Mercer College of Pharmacy

 Preeclampsia is a disorder that can lead to hypertension in pregnancy and is often accompanied with a significant amount of protein excreted in the urine. [1] It has been considered to be an important cause of both maternal and prenatal death [2] and affects approximately 5–8% of all pregnancies worldwide [3]. Placental anti-angiogenic factors may play a central role in the vascular dysfunction that leads to this disorder. [4 The American College of Obstetricians and Gynecologist recommends the use of aspirin in women with a history of preeclampsia in either more than one pregnancy or those that resulted in a delivery prior to 34 weeks gestation. This study explored the reduction in incidence of preeclampsia, in high risk pregnancies, starting from 11 to 14 weeks and continuing through the 36th week of gestation. [5]

Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia [5]
Design Multicenter, double-blind, placebo-controlled trial; N = 1,620
Objective To compare the incidence of preeclampsia from 11-14 weeks until 36 weeks of gestation after treatment with either 150 mg/day aspirin or placebo
Study Groups Aspirin (n = 798); placebo (n = 822)
Methods Women with singleton pregnancies that were at high risk for preterm preeclampsia received 150 mg aspirin per day, or placebo starting from 11 to 14 weeks of gestation and continuing until 36 weeks gestation. The incidence of preeclampsia before 37 weeks of gestation was analyzed based on the intention to treat principle. Participants had to be > 18 years of age. The risk of preeclampsia was assessed by an algorithm that combined maternal factors, mean arterial pressure, uterine-artery pulsatility, etc
Duration One year
Primary Outcome Measure Delivery with preeclampsia before 37 weeks of gestation.
Baseline Characteristics
Characteristic Aspirin Group

(n = 798)

Placebo Group

(n = 822)

Gestational age at randomization — wk
Median 12.7 12.6
Interquartile range 12.3–13.1 12.3–13.0
Age — yr
Median 31.5 31.4
Interquartile range 27.3–35.8 26.9–35.8
Body-mass index
Median 26.7 26.5
Interquartile range 23.3–31.1 23.0–31.5
Race or ethnic group — no. (%)
White 528 (66.2) 559 (68.0)
Black 208 (26.1) 201 (24.5)
South Asian 37 (4.6) 37 (4.5)
East Asian 13 (1.6) 16 (1.9)
Mixed race 12 (1.5) 9 (1.1)
Method of conception — no. (%)
Natural 747 (93.6) 779 (94.8)
Assisted by use of ovulation drugs 6 (0.8) 7 (0.9)
In vitro fertilization 45 (5.6) 36 (4.4)
Cigarette smoking — no. (%) 57 (7.1) 59 (7.2)
Mother had preeclampsia — no. (%) 66 (8.3) 74 (9.0)
Medical history — no. (%)
Chronic hypertension 49 (6.1) 61 (7.4)
Systemic lupus erythematosus 3 (0.4) 1 (0.1)
Antiphospholipid syndrome 2 (0.3) 2 (0.2)
Diabetes mellitus type 1 7 (0.9) 2 (0.2)
Diabetes mellitus type 2 8 (1.0) 8 (1.0)
Obstetrical history — no. (%)
Nulliparous 547 (68.5) 543 (66.1)
Multiparous without preeclampsia 164 (20.6) 195 (23.7)
Multiparous with preeclampsia 87 (10.9) 84 (10.2)
Interval from last pregnancy — yr
Median 4.2 4.6
Interquartile range 2.5–7.0 2.9–7.5
Gestational age at delivery of last pregnancy — wk 39 (37–40) 39 (36–40)
Risk of preterm preeclampsia as assessed at screening
at 11–13 wk (95% CI) — %§ 2.3 (1.4–4.8) 2.6 (1.5–4.8)
Results
Outcome Aspirin Group (n = 798) Placebo Group

(n = 822)

Odds Ratio (95% or 99% CI)
Primary outcome: preterm preeclampsia at <37 wk of

gestation — no. (%)

13 (1.6) 35 (4.3) 0.38

(0.20–0.74)

Adverse Events Common adverse events: N/A
Serious adverse events: ≥ 37 weeks: Preeclampsia (6.6% aspirin and 7.2% placebo), gestational hypertension (9.0% aspirin and 7.5% placebo), stillbirth without preeclampsia (0.3% aspirin and 0.2% placebo), spontaneous delivery < 37 weeks: 5.0% aspirin and 6.0% placebo, miscarriage or stillbirth < 37 weeks: 1.8% aspirin and 2.3% placebo.
Percentage that discontinued due to adverse events: Maternal death due to embolism: 0% in aspirin group and 0.1% placebo
Study Author Conclusions Women with singleton pregnancies that were high risk for preterm preeclampsia had a lower incidence when administered aspirin 150 mg per day, compared to placebo.

Treatment with 150 mg aspirin per day resulted in a significantly lower incidence of preeclampsia when compared with placebo. [5] It also appears to be an important contribution in protecting pregnant women and their babies against the dangers of preeclampsia.

Compliance was measured by reporting the tablet counts during telephone interviews which may have led to bias by the possibility of patients relying on memory or either over- or underestimating how many tablets were actually used. Also, the study was powered for the primary outcome and not for incidence of pregnancy complications, adverse fetal or neonatal outcomes. Therefore, further studies may be useful to determine statistical differences in the incidence of adverse events between the two groups.

 References:

[1] Al-jameil N, Aziz khan F, Fareed khan M, Tabassum H. A brief overview of preeclampsia. J Clin Med Res. 2014;6(1):1-7.

[2] Arulkumaran N, Lightstone L. Severe pre-eclampsia and hypertensive crises. Best Pract Res Clin Obstet Gynaecol. 2013;27(6):877-84.

[3] Jim B, Karumanchi SA. Preeclampsia: Pathogenesis, Prevention, and Long-Term Complications. Semin Nephrol. 2017;37(4):386-397.

[4] Tomimatsu T, Mimura K, Endo M, Kumasawa K, Kimura T. Pathophysiology of preeclampsia: an angiogenic imbalance and long-lasting systemic vascular dysfunction. Hypertens Res. 2017;40(4):305-310.

[5] Rolnik DL, Wright D, Poon LC, et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017;377(7):613-622.

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