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BMJ (Clinical Research Ed.) Apr 2016To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of pre-eclampsia.
DESIGN
Systematic review and meta-analysis of cohort studies.
DATA SOURCES
PubMed and Embase databases, 2000-15.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Cohort studies with ≥ 1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤ 16 weeks' gestation.
DATA EXTRACTION
Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors.
RESULTS
There were 25,356,688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.
CONCLUSIONS
There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at "high risk" of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.
Topics: Aspirin; Body Mass Index; Chronic Disease; Cohort Studies; Early Diagnosis; Female; Humans; Hypertension, Pregnancy-Induced; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy in Diabetics; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Risk Factors
PubMed: 27094586
DOI: 10.1136/bmj.i1753 -
Pharmacotherapy Apr 2022Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the... (Review)
Review
Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%-74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3-5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%-67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.
Topics: Anticoagulants; Drug Interactions; Humans; Platelet Aggregation Inhibitors; Rifabutin; Rifampin; Rifamycins; Warfarin
PubMed: 35152432
DOI: 10.1002/phar.2672 -
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 -
Thrombosis and Haemostasis Jun 2023Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes.
METHODS
We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy.
RESULTS
Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included. Compared with enoxaparin, FXI inhibitors were associated with reduced any-bleeding (risk ratio [RR]: 0.49, 95% confidence interval [CI]: 0.31-0.77), no difference in major bleeding (RR: 0.96, 95% CI: 0.41-2.28), and reduced trial-defined efficacy endpoint (RR: 0.62, 95% CI: 0.49-0.79), the latter driven by the high-dose regimens. Compared with DOACs, FXI inhibitors were associated with a trend toward reduced any-bleeding (RR: 0.66, 95% CI: 0.31-1.38) and no difference in major bleeding (RR: 1.03, 95% CI: 0.22-4.78) or in trial-defined efficacy endpoint (RR: 1.23, 95% CI: 0.88-1.70). Compared with placebo, FXI inhibitors were associated with increased any-bleeding (RR: 1.25, 95% CI: 1.08-1.43) and a trend toward increased major bleeding (RR: 1.21, 95% CI: 0.75-1.93), both driven by high-dose regimens, with no difference in trial-defined efficacy endpoint (RR: 1.02, 95% CI: 0.92-1.13).
CONCLUSION
Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy.
STUDY REGISTRATION
This study is registered in PROSPERO (CRD42022367706).
Topics: Humans; Enoxaparin; Factor XI; Platelet Aggregation Inhibitors; Anticoagulants
PubMed: 36841245
DOI: 10.1055/a-2043-0346 -
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 -
The Cochrane Database of Systematic... Oct 2019Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia.
OBJECTIVES
To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review.
SELECTION CRITERIA
All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups.
AUTHORS' CONCLUSIONS
Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.
Topics: Aspirin; Female; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Maternal Mortality; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic
PubMed: 31684684
DOI: 10.1002/14651858.CD004659.pub3 -
Stroke Jun 2021Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND PURPOSE
Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke.
METHODS
We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model.
RESULTS
Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68–0.83]; P<0.001; I2=0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14–4.34], P=0.02, I2=46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69–0.84], P<0.001, I2=0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67–0.82], P<0.001, I2=0%).
CONCLUSIONS
As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.
Topics: Aspirin; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Time-to-Treatment
PubMed: 33902301
DOI: 10.1161/STROKEAHA.120.033033 -
JAMA Cardiology May 2024Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor.
OBJECTIVE
To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI.
DATA SOURCES
MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction.
STUDY SELECTION
Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI.
DATA EXTRACTION AND SYNTHESIS
Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data.
MAIN OUTCOMES AND MEASURES
The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding.
RESULTS
Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.
Topics: Ticagrelor; Percutaneous Coronary Intervention; Humans; Clopidogrel; Platelet Aggregation Inhibitors; Dual Anti-Platelet Therapy; Purinergic P2Y Receptor Antagonists; Hemorrhage
PubMed: 38506796
DOI: 10.1001/jamacardio.2024.0133 -
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 -
American Journal of Obstetrics and... Feb 2022This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities.
OBJECTIVE
This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities.
STUDY ELIGIBILITY CRITERIA
Relevant national and international clinical practice guidelines, 2009-19, published in English, French, Dutch or German.
STUDY APPRAISAL AND SYNTHESIS METHODS
Following published methods and prospective registration (CRD42019123787), a literature search was updated. CPGs were identified by 2 authors independently who scored quality and usefulness for practice (Appraisal of Guidelines for Research and Evaluation II instrument), abstracted data, and resolved any disagreement by consensus.
RESULTS
Of note, 15 of 17 identified clinical practice guidelines (4 international) were deemed "clinically useful" and had recommendations abstracted. The highest Appraisal of Guidelines for Research and Evaluation II scores were from government organizations, and scores have improved over time. The following were consistently recommended: (1) automated blood pressure measurement with devices validated for pregnancy and preeclampsia, reflecting increasing recognition of the prevalence of white-coat hypertension and the potential usefulness of home blood pressure monitoring; (2) use of dipstick proteinuria testing for screening followed by quantitative testing by urinary protein-to-creatinine ratio or 24-hour urine collection; (3) key definitions and most aspects of classification, including a broad definition of preeclampsia (which includes proteinuria and maternal end-organ dysfunction, including headache and visual symptoms and laboratory abnormalities of platelets, creatinine, or liver enzymes) and a recognition that it can worsen after delivery; (4) preeclampsia prevention with aspirin; (5) treatment of severe hypertension, most commonly with intravenous labetalol, oral nifedipine, or intravenous hydralazine; (6) treatment for nonsevere hypertension when undertaken, with oral labetalol (in particular), methyldopa, or nifedipine, with recommendations against the use of renin-angiotensin-aldosterone inhibitors; (7) magnesium sulfate for eclampsia treatment and prevention among women with "severe" preeclampsia; (8) antenatal corticosteroids for preterm birth but not hemolysis, elevated liver enzymes, and low platelet count syndrome; (9) delivery at term for preeclampsia; (10) a focus on usual labor and delivery care but avoidance of ergometrine; and (11) an appreciation that long-term health complications are increased in incidence, mandating lifestyle change and risk factor modification. Lack of uniformity was seen in the following areas: (1) the components of a broad preeclampsia definition (specifically respiratory and gastrointestinal symptoms, fetal manifestations, and biomarkers), what constitutes severe preeclampsia, and whether the definition has utility because at present what constitutes severe preeclampsia by some guidelines that mandate proteinuria now defines any preeclampsia for most other clinical practice guidelines; (2) how preeclampsia risk should be identified early in pregnancy, and aspirin administered for preeclampsia prevention, because multivariable models (with biomarkers and ultrasonography added to clinical risk markers) used in this way to guide aspirin therapy can substantially reduce the incidence of preterm preeclampsia; (3) the value of calcium added to aspirin for preeclampsia prevention, particularly for women with low intake and at increased risk of preeclampsia; (4) emerging recommendations to normalize blood pressure with antihypertensive agents even in the absence of comorbidities; (5) fetal neuroprotection as an indication for magnesium sulfate in the absence of "severe" preeclampsia; and (6) timing of birth for chronic and gestational hypertension and preterm preeclampsia.
CONCLUSION
Consistent recommendations should be implemented and audited. Inconsistencies should be the focus of research.
Topics: Anticonvulsants; Antihypertensive Agents; Aspirin; Calcium; Delivery, Obstetric; Female; Glucocorticoids; Humans; Hypertension, Pregnancy-Induced; Magnesium Sulfate; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Proteinuria; Risk Assessment
PubMed: 32828743
DOI: 10.1016/j.ajog.2020.08.018