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JAMA Jan 2019The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk.
OBJECTIVE
To assess the association of aspirin use for primary prevention with cardiovascular events and bleeding.
DATA SOURCES
PubMed and Embase were searched on Cochrane Library Central Register of Controlled Trials from the earliest available date through November 1, 2018.
STUDY SELECTION
Randomized clinical trials enrolling at least 1000 participants with no known cardiovascular disease and a follow-up of at least 12 months were included. Included studies compared aspirin use with no aspirin (placebo or no treatment).
DATA EXTRACTION AND SYNTHESIS
Data were screened and extracted independently by both investigators. Bayesian and frequentist meta-analyses were performed.
MAIN OUTCOMES AND MEASURES
The primary cardiovascular outcome was a composite of cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. The primary bleeding outcome was any major bleeding (defined by the individual studies).
RESULTS
A total of 13 trials randomizing 164 225 participants with 1 050 511 participant-years of follow-up were included. The median age of trial participants was 62 years (range, 53-74), 77 501 (47%) were men, 30 361 (19%) had diabetes, and the median baseline risk of the primary cardiovascular outcome was 9.2% (range, 2.6%-15.9%). Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).
CONCLUSIONS AND RELEVANCE
The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.
Topics: Aspirin; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Primary Prevention; Risk
PubMed: 30667501
DOI: 10.1001/jama.2018.20578 -
American Journal of Preventive Medicine Jul 2021Low-dose aspirin is used for pre-eclampsia prophylaxis during pregnancy, but a study that comprehensively investigates both maternal and perinatal outcomes from aspirin... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Low-dose aspirin is used for pre-eclampsia prophylaxis during pregnancy, but a study that comprehensively investigates both maternal and perinatal outcomes from aspirin administration utilizing stratification methods is lacking. The aim of this study is to comprehensively investigate the maternal and neonatal outcomes related to aspirin prophylaxis during pregnancy in relation to dose and therapy initiation by utilizing a stratification method.
EVIDENCE ACQUISITION
Placebo-controlled randomized trials investigating the effect of low-dose aspirin on maternal or perinatal outcomes with sufficient raw data and published in English from inception to August 2020 were searched for from PubMed, Embase, Cochrane Library, and Google Scholar in accordance with PRISMA guidelines. Review articles, editorials, case reports, conference abstracts, and nonplacebo-controlled studies were excluded.
EVIDENCE SYNTHESIS
A total of 35 placebo-controlled randomized trials with 46,568 pregnant women were included in this meta-analysis. Aspirin prophylaxis substantially lowered the risk of pre-eclampsia, preterm birth, perinatal mortality, and intrauterine growth retardation without elevated bleeding risks. Low-dose aspirin considerably enhanced neonatal birth weight but did not decrease the risk of gestational hypertension. The subgroup analysis revealed substantially reduced pre-eclampsia risk and enhanced birth weight and gestational age at delivery in women who initiated aspirin before 20 weeks of gestation (RR=0.76, 95% CI=0.64, 0.90, p=0.001). However, the effect of aspirin dose on pregnancy outcomes was insignificant and requires further evaluation.
CONCLUSIONS
Initiation of low-dose aspirin administration before 20 weeks of gestation considerably decreases the incidence of pre-eclampsia and related neonatal outcomes without increasing bleeding risk.
Topics: Aspirin; Female; Gestational Age; Humans; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 33795180
DOI: 10.1016/j.amepre.2021.01.032 -
American Journal of Obstetrics and... Mar 2018Metaanalyses of randomized controlled trials have reported contradictory results about the effect of aspirin in the prevention of preeclampsia, both in terms of the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE DATA
Metaanalyses of randomized controlled trials have reported contradictory results about the effect of aspirin in the prevention of preeclampsia, both in terms of the gestational age at the onset of treatment and the dose of the drug. The controversy may be resolved by a metaanalysis that includes several recently published trials and particularly the large Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention trial and by examination of whether there is a difference of the effect of aspirin on preterm vs term preeclampsia.
STUDY
We performed a systematic review and metaanalysis that evaluated the prophylactic effect of aspirin during pregnancy.
STUDY APPRAISAL AND SYNTHESIS METHODS
We completed a literature search through PubMed, Cinhal, Embase, Web of Science, and Cochrane library from 1985 to June 2017. Relative risks with random effect were calculated with their 95% confidence intervals.
RESULTS
Sixteen trials that included 18,907 participants provided data for preterm and term preeclampsia. Eight of the included studies were evaluated as being of good quality, and the other 8 studies were deemed to be of poor or uncertain quality. There was high heterogeneity within studies (I >50%) for preterm and term preeclampsia, but no heterogeneity was found in the subgroup of preterm preeclampsia when the onset of treatment was ≤16 weeks of gestation and the daily dose of aspirin was ≥100 mg (I=0%). Administration of aspirin was associated with reduction in the risk of preterm preeclampsia (relative risk, 0.62; 95% confidence interval, 0.45-0.87), but there was no significant effect on term preeclampsia (relative risk, 0.92; 95% confidence interval, 0.70-1.21). The reduction in preterm preeclampsia was confined to the subgroup in which aspirin was initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg (relative risk, 0.33; 95% confidence interval, 0.19-0.57). This effect was also observed in the high-quality studies. The reduction in preterm preeclampsia that was observed in the largest trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention; n=1620; relative risk, 0.38; 95% confidence interval, 0.20-0.72) was similar to that in the 5 smaller trials in which aspirin was initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg (n=639; relative risk, 0.22; 95% confidence interval, 0.07-0.66).
CONCLUSION
Aspirin reduces the risk of preterm preeclampsia, but not term preeclampsia, and only when it is initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg.
Topics: Aspirin; Cyclooxygenase Inhibitors; Female; Gestational Age; Humans; Pre-Eclampsia; Pregnancy
PubMed: 29138036
DOI: 10.1016/j.ajog.2017.11.561 -
JAMA Internal Medicine Mar 2020Patients undergoing total hip replacement (THR) and total knee replacement (TKR) receive venous thromboembolism (VTE) pharmacoprophylaxis. It is unclear which... (Meta-Analysis)
Meta-Analysis
Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement: A Systematic Review and Meta-analysis of Randomized Clinical Trials.
IMPORTANCE
Patients undergoing total hip replacement (THR) and total knee replacement (TKR) receive venous thromboembolism (VTE) pharmacoprophylaxis. It is unclear which anticoagulant is preferable. Observational data suggest aspirin provides effective VTE prophylaxis.
OBJECTIVE
To assess the effectiveness and safety of aspirin for VTE prophylaxis after THR and TKR.
DATA SOURCES
A systematic review and meta-analysis was performed of randomized clinical trials (RCTs), with no language restrictions, from inception to September 19, 2019, using MEDLINE, Embase, Web of Science, Cochrane Library, and bibliographic searches. The computer-based searches combined terms and combinations of keywords related to the population (eg, hip replacement, knee replacement, hip arthroplasty, and knee arthroplasty), drug intervention (eg, aspirin, heparin, clexane, dabigatran, rivaroxaban, and warfarin), and outcome (eg, venous thromboembolism, deep vein thrombosis, pulmonary embolism, and bleeding) in humans.
STUDY SELECTION
This study included RCTs assessing the effectiveness and safety of aspirin for VTE prophylaxis compared with other anticoagulants in adults undergoing THR and TKR. The RCTs with a placebo control group were excluded. The searches and study selection were independently performed.
DATA EXTRACTION AND SYNTHESIS
This study followed PRISMA recommendations and used the Cochrane Collaboration's risk of bias tool. Data were screened and extracted independently by both reviewers. Study-specific relative risks (RRs) were aggregated using random-effects models. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
MAIN OUTCOMES AND MEASURES
The primary outcome was any postoperative VTE (asymptomatic or symptomatic). Secondary outcomes were adverse events associated with therapy, including bleeding.
RESULTS
Of 437 identified articles, 13 RCTs were included (6060 participants; 3466 [57.2%] women; mean age, 63.0 years). The RR of VTE after THR and TKR was 1.12 (95% CI, 0.78-1.62) for aspirin compared with other anticoagulants. Comparable findings were observed for deep vein thrombosis (DVT) (RR, 1.04; 95% CI, 0.72-1.51) and pulmonary embolism (PE) (RR, 1.01; 95% CI, 0.68-1.48). The risk of adverse events, including major bleeding, wound hematoma, and wound infection, was not statistically significantly different in patients receiving aspirin vs other anticoagulants. When analyzing THRs and TKRs separately, there was no statistically significant difference in the risk of VTE, DVT, and PE between aspirin and other anticoagulants. Aspirin had a VTE risk not statistically significantly different from low-molecular-weight heparin (RR, 0.76; 95% CI, 0.37-1.56) or rivaroxaban (RR, 1.52; 95% CI, 0.56-4.12). The quality of the evidence ranged from low to high.
CONCLUSIONS AND RELEVANCE
In terms of clinical effectiveness and safety profile, aspirin did not differ statistically significantly from other anticoagulants used for VTE prophylaxis after THR and TKR. Future trials should focus on noninferiority analysis of aspirin compared with alternative anticoagulants and cost-effectiveness.
Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Fibrinolytic Agents; Humans; Postoperative Complications; Treatment Outcome; Venous Thromboembolism
PubMed: 32011647
DOI: 10.1001/jamainternmed.2019.6108 -
The Journal of Allergy and Clinical... Apr 2022Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis.
BACKGROUND
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.
OBJECTIVE
We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP.
METHODS
We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334.
RESULTS
Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] -19.91 [95% confidence interval (CI) -22.50, -17.32]), omalizumab (MD -16.09 [95% CI -19.88, -12.30]), mepolizumab (MD -12.89 [95% CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]), and benralizumab (MD -7.68 [95% CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] -16.35% [95% CI -18.13, -13.48]), omalizumab (RD -7.40% [95% CI -11.04, -2.43]), mepolizumab (RD -12.33% [95% CI -15.56, -7.22]), and ASA-D (RD -16.00% [95% CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7.
CONCLUSIONS
Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Aspirin; Chronic Disease; Humans; Nasal Polyps; Network Meta-Analysis; Omalizumab; Quality of Life; Sinusitis
PubMed: 34543652
DOI: 10.1016/j.jaci.2021.09.009 -
American Journal of Obstetrics and... Feb 2017Preeclampsia and fetal growth restriction are major causes of perinatal death and handicap in survivors. Randomized clinical trials have reported that the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preeclampsia and fetal growth restriction are major causes of perinatal death and handicap in survivors. Randomized clinical trials have reported that the risk of preeclampsia, severe preeclampsia, and fetal growth restriction can be reduced by the prophylactic use of aspirin in high-risk women, but the appropriate dose of the drug to achieve this objective is not certain.
OBJECTIVE
We sought to estimate the impact of aspirin dosage on the prevention of preeclampsia, severe preeclampsia, and fetal growth restriction.
STUDY DESIGN
We performed a systematic review and meta-analysis of randomized controlled trials comparing the effect of daily aspirin or placebo (or no treatment) during pregnancy. We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials up to December 2015, and study bibliographies were reviewed. Authors were contacted to obtain additional data when needed. Relative risks for preeclampsia, severe preeclampsia, and fetal growth restriction were calculated with 95% confidence intervals using random-effect models. Dose-response effect was evaluated using meta-regression and reported as adjusted R. Analyses were stratified according to gestational age at initiation of aspirin (≤16 and >16 weeks) and repeated after exclusion of studies at high risk of biases.
RESULTS
In all, 45 randomized controlled trials included a total of 20,909 pregnant women randomized to between 50-150 mg of aspirin daily. When aspirin was initiated at ≤16 weeks, there was a significant reduction and a dose-response effect for the prevention of preeclampsia (relative risk, 0.57; 95% confidence interval, 0.43-0.75; P < .001; R, 44%; P = .036), severe preeclampsia (relative risk, 0.47; 95% confidence interval, 0.26-0.83; P = .009; R, 100%; P = .008), and fetal growth restriction (relative risk, 0.56; 95% confidence interval, 0.44-0.70; P < .001; R, 100%; P = .044) with higher dosages of aspirin being associated with greater reduction of the 3 outcomes. Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of preeclampsia (relative risk, 0.81; 95% confidence interval, 0.66-0.99; P = .04) without relationship with aspirin dosage (R, 0%; P = .941). Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose-response effect for severe preeclampsia (relative risk, 0.85; 95% confidence interval, 0.64-1.14; P = .28; R, 0%; P = .838) and fetal growth restriction (relative risk, 0.95; 95% confidence interval, 0.86-1.05; P = .34; R, not available; P = .563).
CONCLUSION
Prevention of preeclampsia and fetal growth restriction using aspirin in early pregnancy is associated with a dose-response effect. Low-dose aspirin initiated at >16 weeks' gestation has a modest or no impact on the risk of preeclampsia, severe preeclampsia, and fetal growth restriction. Women at high risk for those outcomes should be identified in early pregnancy.
Topics: Aspirin; Dose-Response Relationship, Drug; Female; Fetal Growth Retardation; Humans; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Severity of Illness Index
PubMed: 27640943
DOI: 10.1016/j.ajog.2016.09.076 -
American Journal of Obstetrics and... Apr 2023This systematic review and meta-analysis investigated whether the use of low-dose aspirin during pregnancy by women with chronic hypertension reduces the odds of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and meta-analysis investigated whether the use of low-dose aspirin during pregnancy by women with chronic hypertension reduces the odds of superimposed preeclampsia and poor perinatal outcomes.
DATA SOURCES
In September 2021, the following sources were searched: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and EU Clinical Trials Register. Only human studies were included, with no time or language restrictions.
STUDY ELIGIBILITY CRITERIA
Cohort, case-control, and randomized controlled studies reporting women with chronic hypertension pregnant with a singleton were included. Eligible studies compared low-dose aspirin use during pregnancy with a control arm.
METHODS
Risk of bias was assessed using the RoB 2 and ROBINS-I tools. A meta-analysis was performed using a random-effects model, estimating odds ratios and 95% confidence and prediction intervals, and the quality of data was assessed with the GRADE approach. Heterogeneity was investigated in regard to study methodology, timing of commencement of aspirin, and the outcome of preterm preeclampsia.
RESULTS
Nine studies (3 retrospective cohort studies and 6 randomized trials) including 2150 women with chronic hypertension were included. Low-dose aspirin prophylaxis did not significantly reduce the odds of superimposed preeclampsia in the randomized controlled trials (odds ratio, 0.83; 95% confidence interval, 0.55-1.25; prediction interval, 0.27-2.56; low-quality evidence) or observational studies (odds ratio, 1.21; 95% confidence interval, 0.78-1.87; prediction interval, 0.07-20.80; very low-quality evidence). Low-dose aspirin also did not reduce the odds of preterm preeclampsia (odds ratio, 1.17; 95% confidence interval, 0.74-1.86), and early aspirin initiation had no significant impact. There was no significant effect on small-for-gestational-age neonates or perinatal mortality; however, there was a significant reduction in preterm birth (odds ratio, 0.63; 95% confidence interval, 0.45-0.89; moderate-quality evidence). The quality of the evidence is limited by heterogeneity and risk of bias.
CONCLUSION
This meta-analysis was unable to demonstrate a significant change in the odds of superimposed preeclampsia, small-for-gestational-age infants, or perinatal mortality with the use of low-dose aspirin in women with chronic hypertension. However, significant reduction in preterm birth justifies the continued use of aspirin prophylaxis. This work was prospectively registered on the International Prospective Register of Systematic Reviews (registration number CRD42021285921).
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pre-Eclampsia; Premature Birth; Retrospective Studies; Aspirin; Perinatal Death; Hypertension
PubMed: 36209937
DOI: 10.1016/j.ajog.2022.09.046 -
Advances in Therapy Jan 2020International guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
International guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence of the benefit and harm associated with specific low molecular weight heparins such as enoxaparin is dated. No current systematic review and meta-analysis describing the safety and efficacy of enoxaparin for thromboembolism and thromboprophylaxis during pregnancy exists.
METHODS
PubMed, Embase, and Cochrane databases were searched on August 17, 2018 for clinical trials or observational studies in pregnant women receiving enoxaparin; patients with a prosthetic heart valve were excluded. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model, and heterogeneity was measured using the I statistic.
RESULTS
Of the 485 records identified in the search, 24 studies published clinical trials, and observational studies were found dating back to 2000. Only one observational cohort and one randomized control trial focused on the use of enoxaparin for thromboprophylaxis and therefore efficacy was not assessed; the other studies included women with recurrent pregnancy loss (15 studies), history of placental vascular complications (five studies), and recurrent in vitro fertilization failure (two studies) and were therefore analyzed in terms of safety only. Bleeding events were non-significantly more often reported for enoxaparin compared to untreated controls (RR 1.35 [0.88-2.07]) but less often reported for enoxaparin versus aspirin (RR 0.93 [0.62-1.39]); thromboembolic events, thrombocytopenia, and teratogenicity were rarely reported events; in patients with a history of recurrent pregnancy loss, encouragingly the rates of pregnancy loss were significantly lower for enoxaparin compared to untreated controls (RR 0.58 [0.34-0.96]) and enoxaparin + aspirin versus aspirin alone (RR 0.42 [0.32-0.56]) as well as observably lower for enoxaparin versus aspirin alone (RR 0.39 [0.15-1.01]), though significant heterogeneity was observed (I > 60).
CONCLUSION
Literature on the efficacy and safety of enoxaparin for thromboembolism and thromboprophylaxis remains scanty, and therefore efficacy was not assessed; in terms of safety, when including other indications for enoxaparin in pregnancy, we found that enoxaparin was associated with significantly lower complications than aspirin. Given differences in study design and study heterogeneity, pregnancy loss results should be interpreted with caution. Moreover, reports of thromboembolic events, thrombocytopenia, and congenital malformations were rare.
FUNDING
Sanofi.
Topics: Anticoagulants; Aspirin; Enoxaparin; Female; Hemorrhage; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Venous Thromboembolism
PubMed: 31673991
DOI: 10.1007/s12325-019-01124-z -
American Journal of Obstetrics &... Jul 2023This study aimed to compare 2 aspirin dosage regimens for the prevention of preterm preeclampsia (PE): 75 to 81 mg vs 150 to 162 mg taken daily starting in the first... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to compare 2 aspirin dosage regimens for the prevention of preterm preeclampsia (PE): 75 to 81 mg vs 150 to 162 mg taken daily starting in the first trimester of pregnancy.
DATA SOURCES
A systematic search was performed using PubMed, Embase, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials from January 1985 to April 2023.
STUDY ELIGIBILITY CRITERIA
The inclusion criteria were randomized controlled trials that compared the effect of 2 aspirin dosage regimens during pregnancy for the prevention of PE initiated in the first trimester of pregnancy. The intervention was an aspirin dosage between 150 and 162 mg daily, and the control was an aspirin dosage between 75 and 81 mg daily.
METHODS
Of note, 2 reviewers independently screened all citations, selected studies, and evaluated the risk of bias. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool. The corresponding authors of the included studies were contacted to validate each of the collected results. The primary outcome was the risk of preterm preeclampsia, and the secondary outcomes included term preeclampsia, any preeclampsia regardless of gestational age, and severe preeclampsia. Relative risks with their 95% confidence interval were calculated for each study and pooled for global analysis.
RESULTS
Of note, 4 randomized controlled trials were retrieved involving 552 participants. Moreover, 2 randomized controlled trials were at unclear risk of bias, 1 trial at low risk of bias and 1 trial at high risk of bias, which did not have the information for the primary outcome. The pooled analysis demonstrated that an aspirin dosage of 150 to 162 mg was associated with a significant reduction of preterm preeclampsia, compared with an aspirin dosage of 75 to 81 mg (3 studies; 472 participants; relative risk, 0.34; 95% confidence interval, 0.15-0.79; P=.01; I=0%). There was no significant effect on the risk of term preeclampsia (3 studies; 472 participants; relative risk, 0.57; 95% confidence interval, 0.12-2.64; P=.48; I=64%) and all preeclampsia (4 studies; 552 participants; relative risk, 0.42; 95% confidence interval, 0.17-1.05; P=.06; I=58%), but there was a reduction of severe preeclampsia (3 studies; 472 participantst; RR, 0.23; 95% CI, 0.09-0.62; P=.003; I=0%).
CONCLUSION
When initiated in the first trimester of pregnancy, an aspirin dosage of 150 to 162 mg daily was associated with a lower risk of preterm PE than an aspirin dosage of 75 to 81 mg daily. However, the lack of large, high-quality studies limited the clinical scope of the current results taken alone.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Aspirin; Pre-Eclampsia; Platelet Aggregation Inhibitors; Pregnancy Trimester, First; Gestational Age
PubMed: 37146687
DOI: 10.1016/j.ajogmf.2023.101000 -
JAMA Sep 2021Preeclampsia is a hypertensive disorder of pregnancy that poses serious maternal and infant health risks. Previous systematic reviews have established benefits of...
IMPORTANCE
Preeclampsia is a hypertensive disorder of pregnancy that poses serious maternal and infant health risks. Previous systematic reviews have established benefits of low-dose aspirin taken during pregnancy to prevent preeclampsia and its sequelae.
OBJECTIVE
To update evidence for the US Preventive Services Task Force (USPSTF) on effectiveness of aspirin use in preventing preeclampsia in individuals at increased risk based on clinical risk factors or measurements associated with higher disease incidence than in the general population.
DATA SOURCES
Studies from previous USPSTF review (2014), literature published January 2013 through May 15, 2020, in MEDLINE, PubMed (for publisher-supplied records only), EMBASE, and Cochrane Central Register of Controlled Trials. Ongoing surveillance through January 22, 2021.
STUDY SELECTION
Good- and fair-quality randomized clinical trials (RCTs) of low-dose aspirin use during pregnancy to prevent preeclampsia among individuals at increased risk; studies conducted in general populations to evaluate potential harms.
DATA EXTRACTION AND SYNTHESIS
Dual article screening and risk-of-bias assessment. Study data abstracted into prespecified forms, checked for accuracy. Random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Diagnosis of preeclampsia; adverse pregnancy health outcomes and complications including eclampsia, perinatal mortality, preterm birth, small for gestational age, and potential bleeding harms or infant/child harms from aspirin exposure.
RESULTS
A total of 23 randomized clinical trials (RCTs) (N = 26 952) were included; 18 were conducted among participants at increased preeclampsia risk. Aspirin dosages ranged from 50 mg/d to 150 mg/d. Most trials enrolled majority White populations selected based on a range of risk factors. The incidence of preeclampsia among the trials of participants at increased risk ranged from 4% to 30%. Aspirin use was significantly associated with lower risk of preeclampsia (pooled relative risk [RR], 0.85 [95% CI, 0.75-0.95]; 16 RCTs [n = 14 093]; I2 = 0%), perinatal mortality (pooled RR, 0.79 [95% CI, 0.66-0.96]; 11 RCTs [n = 13 860]; I2 = 0%), preterm birth (pooled RR, 0.80 [95% CI, 0.67-0.95]; 13 RCTs [n = 13 619]; I2 = 49%), and intrauterine growth restriction (pooled RR, 0.82 [95% CI, 0.68-0.99]; 16 RCTs [n = 14 385]; I2 = 41%). There were no significant associations of aspirin use with risk of postpartum hemorrhage (pooled RR, 1.03 [95% CI, 0.94-1.12]; 9 RCTs [n = 23 133]; I2 = 0%) and other bleeding-related harms, or with rare perinatal or longer-term harms. Absolute risk reductions for preeclampsia associated with aspirin use ranged from -1% to -6% across larger trials (n >300) and were greater in smaller trials. For perinatal mortality, absolute risk reductions ranged from 0.5% to 1.1% in the 3 largest trials.
CONCLUSIONS AND RELEVANCE
Daily low-dose aspirin during pregnancy was associated with lower risks of serious perinatal outcomes for individuals at increased risk for preeclampsia, without evident harms.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age; Perinatal Death; Postpartum Hemorrhage; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 34581730
DOI: 10.1001/jama.2021.8551