Clinical Influence of Nonadherence With Prophylactic Aspirin in Preventing Preeclampsia in High-Risk Pregnancies

Abstract

Aspirin nonadherence and its associated increase in cardiovascular and cerebrovascular events is well described; however, the prevalence of aspirin nonadherence among high-risk pregnant women at risk of preeclampsia and its influence on clinical outcomes remains unclear. Our study examined the prevalence of aspirin nonadherence and resistance among high-risk pregnant women quantitatively (platelet function analyzer 100 and plasma salicylic acid) and clinical outcomes relative to adherence. High-risk pregnant women were recruited across 3 centers in the South West Sydney Local Health District. Simultaneous clinic data, blood sample, and self-reported adherence assessment were prospectively collected at 4-week intervals from 12 to 36 weeks of gestation. Nonadherence was defined as normal platelet function analyzer 100 and nondetectable plasma salicylic acid in <90% of time points. Value of <90% is based on current data. Two hundred twenty women were recruited over 25 months. No woman was aspirin resistant, and 63 (44%) women demonstrated inadequate adherence. Women with inadequate adherence had higher incidence of early-onset preeclampsia (17% versus 2%; odds ratio [OR], 1.9 [95% CI, 1.1–8.7]; P =0.04), late-onset preeclampsia (41% versus 5%; OR, 4.2 [95% CI, 1.4–19.8]; P =0.04), intrauterine growth restriction (29% versus 5%; OR, 5.8; [95% CI, 1.2–8.3]; P =0.001), preterm delivery (27% versus 10%; OR, 5.2 [95% CI, 1.5–8.7]; P =0.008), and higher likelihood of increase in antihypertensives antenatally (60% versus 10%; OR, 4.6 [95% CI, 1.2–10.5]; P =0.003). Kaplan-Meier analysis demonstrated lower incidence of premature delivery in the ≥90% adherent group (HR, 0.3 [95% CI, 0.2–0.5]; P <0.001).Kappa coefficient agreement between qualitative and quantitative assessment of adherence was moderate (κ=0.48; SE=0.029; P <0.0001). Our data demonstrates that aspirin is an effective prophylactic agent with an absolute risk reduction of 51% (number needed to treat, 2) when adherence is ≥90%, compared with women with inadequate adherence. Women who were <90% adherent had higher rates of preeclampsia, intrauterine growth restriction, preterm delivery, and increase in antenatal antihypertensive requirements. Self-reported adherence does not accurately reflect actual adherence.

Factors that influence adherence to aspirin therapy in the prevention of preeclampsia amongst high-risk pregnant women: A mixed method analysis

“…Interviews were ceased at point of qualitative data saturation which was achieved after the sixth interview. Three of these 6 women in the qualitative study were noted to have >90% adherence in the longitudinal study [20] with <90% adherence in the remaining three women. Characteristics of the women invited to participate in the quantitative study and those in the qualitative study are described in Tables 1 and 2 respectively.…”

“…Our study identified two key themes, from a patient's perspective, that influenced adherence with prophylactic aspirin in pregnancy: 1) Pill burden and non-intentional omission and 2) Communication and positive relationship with HCPs (Table 3). We previously demonstrated that, from the women's demographic characteristic perspective, women who had previous preeclampsia and tertiary level education had a higher rate of adherence with aspirin [20,21].…”

“…High-risk pregnant women who were on aspirin as part of a multi-centre longitudinal cohort study [20] within the South Western Sydney Local Health District (SWSLHD), NSW, Australia, were invited to participate in an online survey (SurveyMonkey 1 ). Women included in this study were risk stratified as high-risk for preeclampsia based on the current guidelines [24,25] and were prescribed aspirin (100mgs or 150mgs) by their treating clinicians.…”

“…Women were also invited to express their interest in participating in a one-to-one, face-toface interview for the qualitative assessment. Purposeful selection of the interview participants was done based on the participant's obstetric history and biochemically observed adherence to aspirin [20,21] to gain maximum variation in the sample. The qualitative study was designed based on the quantitative data with the aim of further exploring the data obtain.…”

“…Our observational cohort study, which assessed for adherence quantitatively through plasma salicyclic acid detection and platelet function analyser-100 (PFA-100) assessment, demonstrated that 44% of high-risk women were <90% adherent with aspirin therapy [20]. Women with inadequate adherence demonstrated aa higher rate of both early and late onset preeclampsia with a higher rate of intrauterine fetal growth restriction (IUGR) and preterm delivery in comparison to women who were �90% adherent with aspirin therapy [20,21]. This demonstrated that non-adherence to prophylactic aspirin increases the risk of potentially avoidable maternal and fetal complications in pregnancy.…”