Enoxaparin and Aspirin Compared With Aspirin Alone to Prevent Placenta-Mediated Pregnancy Complications

Haddad, Bassam; Winer, Norbert; Chitrit, Yvon; Houfflin‐Debarge, V.; Chauleur, Céline; Bages, Karine; Tsatsaris, Vassilis; Benachi, Alexandra; Bretelle, Florence; Gris, Jean‐Christophe; Bastuji‐Garin, Sylvie; Investigators, Heparin-Preeclampsia Trial

doi:10.1097/aog.0000000000001673

Cited by 78 publications

(83 citation statements)

References 30 publications

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“…44 It is reassuring that the number of bleeding events in the antepartum and postpartum periods is comparable or lower with the total bleeding rates reported in randomized trials evaluating prophylactic LMWH and ASA during pregnancy or in the postpartum period in women without ET. [45][46][47][48] It is further reassurance that there was no antepartum bleeding reported in women with ET who received a combination of ASA and LMWH during their pregnancies.…”

Section: Discussionmentioning

confidence: 99%

“…Prospective studies or a meta-analysis is still needed to better quantify the risk, if any, of placenta-mediated pregnancy complications in women with ET, including what role ASA, LMWH, or IFN has in preventing pregnancy loss or placenta-mediated complications. In the non-ET population, recent data from randomized controlled trials and an individual patient-level meta-analysis of 963 pregnant women in 8 trials found that there is no role for antepartum ASA or LMWH prophylaxis in preventing pregnancy loss or placenta-mediated pregnancy complications, including those with inherited thrombophilia, 48,[56][57][58][59][60] with the exception of ASA and preeclampsia. 60 Further research evaluating the role of LMWH for the subgroup of women with past placenta abruption is still needed.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Skeith

Carrier

Robinson

et al. 2017

Blood

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We performed a meta-analysis to evaluate the risk of venous thromboembolism (VTE) in pregnant women with essential thrombocythemia. Twenty-one trials and 756 pregnancies met inclusion criteria. The absolute VTE risk in the antepartum period is not above a threshold where low-molecular-weight heparin (LMWH) prophylaxis is clearly indicated or below a threshold where LMWH should be withheld (2.5%; 95% CI, 1.3-4.3). Postpartum, the absolute VTE risk is above a threshold where postpartum LMWH prophylaxis should be considered (4.4%; 95% CI, 1.2-9.5).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Skeith

Carrier

Robinson

et al. 2017

Blood

View full text Add to dashboard Cite

show abstract

“…27 More recent studies have examined the effect of prophylactic anticoagulation in addition to aspirin on placenta-mediated complications with conflicting results. 28–30 The evidence regarding the dose-dependent efficacy and impact of gestational age at initiation are similarly poorly defined. 31, 32 …”

Section: Commentmentioning

confidence: 99%

Impact of USPSTF recommendations for aspirin for prevention of recurrent preeclampsia

Tolcher

Chu

Hollier

et al. 2017

American Journal of Obstetrics and Gynecology

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BACKGROUND The U.S. Preventive Services Task Force (USPSTF) recommends low-dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. Recommendations for the use of aspirin for preeclampsia prevention were issued by the USPSTF in September 2014. OBJECTIVES To evaluate the incidence of recurrent preeclampsia in our cohort before and after the USPSTF recommendation for aspirin for preeclampsia prevention. STUDY DESIGN This is a retrospective cohort study designed to evaluate rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a two hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into two groups, “before” and “after” the release of the USPSTF 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated. RESULTS 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia; 284 women “before” and 133 women “after” the USPSTF recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups (P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before versus 5.3% after; P >.05). Risk factors for recurrent preeclampsia included maternal age >35 years (RR, 1.83; 95% CI, 1.34–2.48), Medicaid insurance (RR, 2.08; 95% CI, 1.15–3.78), type 1 diabetes (RR, 2.13; 95% CI, 1.37–3.33), and chronic hypertension (RR, 1.96; 95% CI, 1.44–2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk (aRR), 0.70; 95% CI, 0.52- 0.95). CONCLUSION Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the USPSTF recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention.

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“…Most recently, the large, well-designed HEPEPE and EPPI trials reported that enoxaparin with ASA does not significantly reduce placental-mediated complications, including preeclampsia, when compared to aspirin alone [31,32]. The conclusions of systematic reviews and meta-analyses summarizing this literature are conflicting.…”

Section: Lmwh For Preeclampsia Prevention: Evidence From Clinical Trialsmentioning

confidence: 84%

“…The criteria utilized to identify women as 'high risk' of developing preeclampsia have thus far differed greatly between trials. The majority of trials utilized inclusion criteria of prior preeclampsia, placental-mediated complication or pregnancy loss to identify women who are considered at high risk of preeclampsia in the current pregnancy; this was the approach in the recent HEPEPE and EPPI trials [31,32]. The primary outcome of these clinical trials has typically consisted of a composite clinical outcome, including preeclampsia, small for gestational age, placental abruption, and maternal or perinatal death.…”

Section: Patient Selectionmentioning

confidence: 99%

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

McLaughlin

Scholten

Parker

et al. 2018

Brit J Clinical Pharma

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Low molecular weight heparin has been extensively evaluated for the prevention of preeclampsia in high-risk pregnant women; however, the results from these trials have been conflicting. This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimize the selection of high-risk women for participation in future trials, and the importance of trial standardization. Preeclampsia preventionPreeclampsia is a hypertensive disorder of pregnancy, clinically diagnosed by new-onset hypertension after 20 weeks' gestation with evidence of organ injury [1]. The potential maternal and perinatal complications of preeclampsia are significant, including maternal seizures, fetal growth restriction (FGR) and stillbirth. Approximately 5% of women develop preeclampsia, with the majority of women experiencing mild preeclampsia that occurs near term and is safely managed by delivery [2]. Only 1% of pregnant women develop early-onset preeclampsia, where both the maternal and fetal implications are substantially greater, typically resulting in FGR and the need for iatrogenic preterm delivery before 34 weeks' gestation [2]. Early-onset preeclampsia is hypothesized to be a direct consequence of the interactions between a dysfunctional placenta and maternal cardiovascular system, while late-onset preeclampsia is hypothesized to be largely triggered by maternal constitutional factors [3][4][5]. Typically, women with early-onset preeclampsia present with an acute, severe syndrome that threatens the life of both the mother and her fetus. In contrast, late-onset preeclampsia is a less severe illness with a favourable clinical outcome in countries with well-developed maternity systems. However, in countries with limited medical resources, preeclampsia remains among the most frequent causes of maternal death [6].The early-and late-onset subsets of preeclampsia exhibit different types and severity of placental pathologies and express divergent maternal haemodynamics. Early-onset preeclampsia is strongly associated with placental disease characterized by maternal vascular malperfusion, where the abnormal placental villi secrete excessive amounts of antiangiogenic proteins and reduced levels of pro-angiogenic proteins into the maternal circulation [7][8][9]. Women with early-onset disease, typically associated with FGR, develop hypertension earlier in pregnancy that is characterized by increased systemic vascular resistance, reduced cardiac output and stroke volume along with relative bradycardia [5]. In contrast, late-onset preeclampsia is less commonly associated with severe placental disease, and consequently exhibits less British Journal of Clinical Pharmacology Br J Clin Pharmacol (2018) 84 673-678 673

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Enoxaparin and Aspirin Compared With Aspirin Alone to Prevent Placenta-Mediated Pregnancy Complications

Abstract: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00986765.

Cited by 78 publications

References 30 publications

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Impact of USPSTF recommendations for aspirin for prevention of recurrent preeclampsia

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

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