This document summarizes a journal club presentation about a study on the efficacy of low-dose aspirin for preeclampsia prevention by ethnicity and race. The study was a secondary analysis of two randomized controlled trials that compared rates of preeclampsia in women receiving aspirin or placebo. The results showed aspirin significantly reduced preeclampsia in low-risk non-Hispanic white women but not in other groups. For high-risk women, aspirin efficacy did not differ by ethnicity/race. The authors concluded that aspirin efficacy may vary between racial/ethnic groups due to differences in aspirin metabolism and pharmacogenetics. Clinical implications are that not all groups may benefit from current low-dose aspirin recommendations

1. HFCSH Clinical pharmacy and DIC
unit
Journal club presentation
By : Salahadin M.Ali
(B.pharm)
6/4/2022
1

2. 2
Low-dose aspirin for preeclampsia
prevention: efficacy by ethnicity and
race
Mary Catherine et al. AmJ Obstet Gynecol MFM
2020;2:100184.

3. Outline
3
 Authors and funding source
 Background
 Objective
 Historical context
 Method
 Research question
 Study outlines
 Inclusion and Exclusion criteria
 Predictive and outcome variables
 Results
 Authors’ Conclusion
 Strength and weakness
 Discussion points
 Conclusion and Recommendations (Applicability & impact on healthcare
providers)

4. Authors and funding source
4
 Authors: Mary Catherine Tolcher, MD, MSc;
Haleh Sangi-Haghpeykar, PhD; Hector
Mendez-Figueroa, MD;Kjersti M. Aagaard, MD,
PhD.
 Funding :??

5. Background
5
 Preeclampsia is a prevalent pregnancy
disorder with significant public health
consequences for both mother and infant.
 Currently, the American College of
Obstetricians and Gynecologists (ACOG) and
the Society for Maternal-Fetal Medicine
recommend low-dose aspirin for the
prevention of preeclampsia among women at
a high risk of developing the disease

6. Cont.….
6
 Risk criteria include
o women with a history of preeclampsia,
o multiple gestations
o chronic hypertension
o pre-gestational diabetes
o renal disease, or autoimmune disorder

7. Objectives
7
 To compare the rates of preeclampsia among low- and high-
risk women who received aspirin compared with placebo for
preeclampsia prevention.

8. Historical Context
8
 The recommendation for aspirin prophylaxis
for women at a high risk of preeclampsia is
based on meta-analyses of randomized trials
that revealed a small but significant reduction
in preeclampsia with aspirin compared with
placebo(1-3).

9. Method
9
 This is a secondary analysis of 2 randomized
controlled trials previously performed by:
 The Maternal-Fetal Medicine Units (MFMU)
Network:
 The Low Risk Aspirin (LRA) study and the
High-Risk Aspirin (HRA) study

10. Research Questions
10
 Why was this study conducted?
 What does this add to what is known?

11. Study outlines
11
 Hypothesis:
the efficacy of aspirin prophylaxis, as
evidenced by the occurrence and severity of
preeclampsia, may be less in non Hispanic
black women.

12. Outcomes
12
 Primary outcomes
The primary outcome of this secondary analysis was the diagnosis of
preeclampsia.
Outcomes were stratified by ethnicity and race (Hispanic, non-Hispanic
white, non-Hispanic black, or other).
 Secondary outcomes
secondary outcomes in this analysis included gestational age at
delivery, preterm delivery, placental abruption, small for gestational
age (SGA), stillbirth, and neonatal death.

13. Inclusion / exclusion criteria
13
 For the Low-Risk Aspirin trial, normotensive,
nulliparous women were enrolled between 13
and 26 weeks’ gestation and randomized to 81
mg aspirin daily or placebo.
 For the High-Risk Aspirin trial, women with pre-
stational insulin-treated diabetes mellitus,
chronic hypertension, multiple gestations, or a
history of preeclampsia in a previous pregnancy
were enrolled between 13 and 26 weeks’
gestation and randomized to 81 mg aspirin daily
or placebo.

14. Data Analysis
14
 Continuous variables were compared using
the 2-sample test if parametric or Wilcoxon
rank-sum test if nonparametric.
 Categorical or binary variables were compared
using chi-square or Fisher exact test as
appropriate.
 All analyses were performed using the SAS
statistical software (version 9.4, SAS Institute,
Cary, NC).
 P<.05 was considered statistically significant
in both unadjusted and adjusted analyses.

15. Result
15
 The LRA study included 3135 women and 3134
with documented ethnicity and race; 1570 were
assigned to the aspirin group and 1564 to the
placebo group.
 The study included 1533 non-Hispanic black
(48.9%), 559 non-Hispanic white women (17.8%),
1018 Hispanic (32.5%), and 24 “other” (0.8%)
women.
 There was no difference between ethnicity and
race when comparing the aspirin and placebo
groups (P=.895)

16. Cont.….
16
 The risk of preeclampsia was significantly reduced
among non-Hispanic white women who received
aspirin compared with non-Hispanic white women
who received placebo (1.1% vs 6.0%; RR, 0.19;
95% CI, 0.06e0.63; P=.007 )
 but not among the Hispanic, non-Hispanic black,
or other ethnicity and race groups.
 The risk of stillbirth was significantly increased
among non-Hispanic black women who received
aspirin compared with non-Hispanic black women
who received placebo (P¼.048).

17. Table1. Outcomes by ethnicity and race in the Low-Risk Aspirin
(LRA) study among women receiving aspirin or placebo for
preeclampsia prevention (n[3134) (Hispanic [n[1018], non-
Hispanic white [n[559], non-Hispanic black [n [1533], other [n[24]).
17
Out come Asprin
group
N=1570
Placebo
group
N=1564
RR(95% CI) P
value
preeclampsia 69 (4.395) 94 (6.010) 0.740
(0.550e1.010)
.052
Hispanic 23 (4.536) 26 (5.088) 0.900
(0.520e1.560)
.716
Non-Hispanic white 3 (1.090) 17 (5.986) 0.190
(0.060e0.630)
.007
Non –Hispanic black 42 (5.405) 50 (6.614) 0.830
(0.560e1.230)
.347
Other 1 (9.091) 1 (7.692 1.180
(0.080e16.78
0)
.900

18. Cont.…..
18
 In the High Risk Aspirin trial of 2539 women,
269 were Hispanic (10.6%), 832 were non-
Hispanic white (32.8%), 1426 were non-
Hispanic black (56.2%), and 12 were
categorized as other (0.5%).
 Stratification by ethnicity and race did not
reveal a decreased incidence of preeclampsia
for any of the subgroups (P>.05). Moreover,
there was no significant difference in other
measured outcomes including preterm delivery
at

19. Author’s Discussion and
Conclusion
19
 When considered with previously published
and recent work these findings presented are
of clinical significance and collectively suggest
that broad, unselective use of aspirin among
low-risk women is not currently supported by
data or national recommendations with
reported potential benefit only among few
women.

20. CONT…
20
 Aspirin undergoes polymorphic metabolism,
both adverse reactions and efficacy may have
significant variation by virtue of common
genetic variants retained in distinct racial and
ethnic populations and their admixtures.
 Non-Hispanic black women exhibit a
disproportionate lack of efficacy of aspirin for
the prevention of recurrent preeclampsia.

21. Cont.….
21
 This findings of a substantial improvement in
the efficacy of aspirin for preventing
preeclampsia among low-risk non-Hispanic
white women support future exploration of the
pharmacogenetics of aspirin metabolism and
the potential impact of genomics-driven aspirin
resistance on preeclampsia prevention

22. Clinical implications
22
 Aspirin resistance (or nonresponse) refers to a
lack of reduction in platelet production of
thromboxane A2 and resultant platelet
activation and aggregation.
 A recently published cohort study evaluated
the impact of implementing the ACOG
endorsed guidelines for aspirin therapy among
pregnant women with chronic hypertension in
a population of a majority of non-Hispanic
black women and failed to observe a
significant decrease in superimposed
preeclampsia.

23. Cont.…
23
 This study further supports the hypothesis that
at-risk non-Hispanic black women may be
either resistant or unresponsive to aspirin or
require a higher dose of aspirin for the
prevention of preeclampsia.
 But national recommendations continue to
support the use of low-dose aspirin
prophylaxis (81 mg/d) for all women at a high
risk of developing preeclampsia

24. Evaluation of Study quality
24
 Strength
• Stated the study limitations
• This finding include historical context
• They stated study hypothesis
• The result were clearly presented
• The researchers/authors are all qualified
• Stated clinical implication

25. Cont.….
25
 Weakness
• The duration of intervention not stated clearly
• There were no sufficient follow-up and
Adherence assessment
• Who funded the study and what was the
sponsor's role in the study not specified.

26. Personal Discussion and
Conclusion
26
 Recommendation from American college of obstetrician and
gynecologist (ACOG) include
 low-dose aspirin (81 mg/day) prophylaxis is recommended in
women at high risk of preeclampsia and should be initiated
between 12 weeks and 28 weeks of gestation (optimally
before 16 weeks) and continued daily until delivery.
 Low-dose aspirin prophylaxis should be considered for
women with more than one of several moderate risk factors
for preeclampsia.
 Low-dose aspirin prophylaxis is not recommended solely for
the indication of prior unexplained stillbirth, in the absence of
risk factors for preeclampsia.

27. Cont.…….
27
 Low-dose aspirin prophylaxis is not
recommended for prevention of fetal growth
restriction, in the absence of risk factors for
preeclampsia.
 Low-dose aspirin prophylaxis is not
recommended for the prevention of
spontaneous preterm birth, in the absence of
risk factors for preeclampsia.
 Low-dose aspirin prophylaxis is not
recommended for the prevention of early
pregnancy loss.

28. Reference
28
1. Henderson JT, et al. Low dose aspirin for prevention of
morbidity and mortality from preeclampsia: a systematic
evidence review for the U.S. Preventive Services Task
Force. Ann Intern Med 2014;160: 695–703.
2. Xu TT, et al Low-dose aspirin for preventing
preeclampsia and its complications: a meta-analysis. J Clin
Hypertens (Greenwich) 2015;17: 567–73.
3. Askie LM, et al .Antiplatelet agents for prevention of pre-
eclampsia: a meta-analysis of individual patient data.
Lancet 2007;369:1791–8.
4. ACOG Committee Opinion no. 743: low-dose aspirin use
during pregnancy. Obstet Gynecol 2018;132:e44–52.

29. 29
Thank you