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📋 Quiz Notes: Recent & Ongoing Trials on Hypertensive Disorders of Pregnancy (HDP)

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SECTION 1 - ASPIRIN FOR PREECLAMPSIA PREVENTION

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1A. ASPREO Trial - Aspirin Dose in Obese Patients (2025)

• Design: Open-label RCT, n=220, BMI ≥30 kg/m², at least 1 high-risk factor (prior PE, stage 1 HTN, pregestational/early-onset GDM)
• Comparison: Aspirin 162 mg/day vs 81 mg/day from 12-20 weeks until delivery
• Primary outcome: Preeclampsia with severe features / eclampsia / HELLP
• Results:
  • 162 mg group: 35% vs 81 mg group: 40% incidence (not statistically significant)
  • Bayesian posterior probability of benefit with 162 mg = 78%
  • Best estimate: 12% relative reduction with 162 mg
  • Side effects were similar between groups
• Conclusion: Insufficient power to confirm superiority; supports a larger multicenter trial
• Key quiz point: Context for NICE UK recommending 150 mg vs ACOG recommending 81 mg in the US; aspirin resistance may matter in obese patients

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1B. First-Trimester Screen-and-Prevent Strategy in Asia (2024)

• Design: Multicenter, stepped wedge cluster RCT across 10 Asian regions (n=48,725 screened)
• Intervention: Bayes theorem-based first-trimester triple-test (MAP + uterine artery PI + PAPP-A); high-risk women (risk ≥1 in 100) received low-dose aspirin <16 weeks to 36 weeks
• Results:
  • No significant reduction in preterm PE comparing intervention vs non-intervention phase overall (aOR 1.59, 95% CI 0.91-2.77) - screening implementation effect was not significant at population level
  • Among high-risk women who actually received aspirin: 41% reduction in preterm PE (aOR 0.59, 0.37-0.92)
  • 54% reduction in PE with delivery <34 weeks
  • 64% reduction in perinatal death
  • Acceptance rate: 88% agreed to screening; 82% of high-risk women took aspirin
• Key quiz point: The FMF first-trimester screening + aspirin strategy works when women receive it, but population-level implementation didn't show statistical significance in this design

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1C. Aspirin Adherence Systematic Review (2025)

• Only 25% of aspirin RCTs clearly reported adherence data
• Most common threshold: ≥80% tablet intake = "good adherence"
• Mean adherence at ≥80% threshold = 79.5%
• Only 2 studies showed association between good adherence and lower PE incidence
• Multi-measure assessment (pill count + interview + TxB2) is recommended
• Key quiz point: Adherence is an underreported and likely important variable in aspirin PE prevention trials

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1D. Network Meta-Analysis: Aspirin Doses vs Heparin (2025)

• Compared diverse aspirin dosages and heparin for placenta-mediated complications
• Low-dose aspirin remains standard; higher doses under investigation for selected populations

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SECTION 2 - ANTIHYPERTENSIVE DRUG TREATMENT IN PREGNANCY

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2A. Oral Antihypertensives in Pregnancy - Network Meta-Analysis (2025)

• 23 RCTs, 3989 women included
• Compared methyldopa, labetalol, nifedipine (vs placebo/no treatment)
• Results:
  • Labetalol and methyldopa both significantly reduced severe hypertension vs placebo (labetalol RR 0.20; methyldopa RR 0.44)
  • Labetalol vs nifedipine: labetalol reduced preeclampsia risk (RR 0.50, 95% CI 0.28-0.87) and preterm birth (RR 0.68, 0.52-0.90)
  • No significant difference on primary outcome (severe HTN) between the three agents head-to-head
• Conclusion: Modest preference for labetalol over nifedipine based on PE and preterm birth outcomes; overall evidence quality was low-moderate
• Key quiz point: Labetalol ≥ nifedipine ≥ methyldopa hierarchy in 2025 evidence

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2B. CHAP Trial Follow-ups - Postpartum BP Control (2024)

• Finding: Women actively treated during pregnancy had better postpartum BP control at 6 weeks (56.7% achieved BP <140/90 vs 51.5% in control; aOR 1.22, 95% CI 1.00-1.48)
• More were prescribed antihypertensives postpartum (81.7% vs 58.4%)
• Key quiz point: Treatment of mild chronic HTN in pregnancy carries over to improved postpartum BP control

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2C. CHAP Trial - Optimal Delivery Timing in Mild Chronic HTN (2024)

• n=1,417 participants with mild chronic HTN at term
• Early-term delivery (37-38 weeks) was NOT associated with reduced adverse maternal outcomes
• Planned delivery at 37 weeks: increased RDS risk (aOR 2.70)
• Delivery at 37 and 38 weeks: increased neonatal hypoglycemia
• Conclusion: Optimal delivery timing in mild chronic HTN = 39 weeks gestation
• Key quiz point: Don't deliver early for mild chronic HTN - wait for 39 weeks

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2D. CHAP Trial - BP Control <130/80 in HTN + Diabetes (2025)

• Among CHAP participants with chronic HTN + diabetes (n=434)
• Women achieving mean BP <130/80 had lower adverse perinatal outcomes (19.3% vs 46.5%; aRR 0.43)
• Specifically: reduced preeclampsia with severe features (aRR 0.35) and preterm birth <35 weeks (aRR 0.44)
• Lower NICU admissions (aRR 0.74)
• Key quiz point: For pregnant patients with both chronic HTN AND diabetes, tighter BP target (<130/80 vs <140/90) appears beneficial

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2E. CHAP Trial - Low BP and SGA Risk (2025)

• Among treated mild chronic HTN patients (n=1,205)
• Only 2.6% had low BP (systolic <110/diastolic <70)
• Low BP was NOT significantly associated with SGA <5th percentile
• Key quiz point: Treating mild chronic HTN to target BP during pregnancy does NOT increase risk of SGA - reassuring safety data

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SECTION 3 - POSTPARTUM HYPERTENSION MANAGEMENT

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3A. Amlodipine vs Nifedipine ER for Postpartum HTN (2025)

• n=175 screened; 132 met antihypertensive initiation criteria
• Primary outcome: Time to discharge from delivery (noninferiority limit = 24 hours)
• Results:
  • Amlodipine: NON-INFERIOR to nifedipine ER (median LOS 73.5h vs 72.0h)
  • No difference in additional antihypertensives needed or side effects
  • Amlodipine: 0% medication discontinuation vs nifedipine ER: 10.1% (p=0.02)
  • Less hypotension and tachycardia with amlodipine
• Key quiz point: Amlodipine is a valid alternative to nifedipine ER for postpartum HTN with better tolerability

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3B. LAPP Trial - Furosemide for De Novo Postpartum HTN (2025)

• Intervention: Oral furosemide 20 mg/day x 5 days vs placebo, starting within 8 hours of delivery
• Primary outcome: Mean arterial pressure in 24h before discharge
• Results: NO significant difference in MAP (furosemide 88.9 ± 7.4 vs placebo 86.8 ± 7.1 mmHg; p=NS)
• 10% developed de novo postpartum HTN in both groups (p=0.71)
• Conclusion: Furosemide does NOT reduce BP or prevent de novo postpartum HTN in high-risk patients without antenatal diagnosis
• Key quiz point: Furosemide prophylaxis doesn't help prevent NEW postpartum HTN (different from patients who already have PE - see 3C)

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3C. Postpartum Furosemide in Established Preeclampsia (2025)

• n=120 women with preeclampsia with severe features / eclampsia (already on MgSO4)
• Intervention: Furosemide 40 mg/day orally x 5 days vs placebo postpartum
• Results:
  • Lower mean daily systolic and diastolic BP in furosemide group (p<0.001)
  • Fewer severe hypertensive episodes on Day 2 and Day 5 (p=0.04)
  • Shorter time to BP control (p=0.01)
• Key quiz point: Contrast with LAPP trial - furosemide DOES help postpartum BP control in women who ALREADY HAVE preeclampsia/eclampsia (vs those at risk but without diagnosis)

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3D. Spironolactone for Postpartum HTN (ONGOING PHASE 2 TRIAL)

• Population: Women with HDP (gestational HTN or preeclampsia) + pre-pregnancy overweight/obesity; NO pre-existing chronic HTN
• Intervention: Spironolactone 25 mg/day x 12 weeks vs placebo (postpartum)
• Primary goal: Reduce BP and improve cardiovascular outcomes by 9 months postpartum
• Rationale: Aldosterone antagonism targets hormonal imbalance contributing to postpartum HTN; different mechanism from methyldopa/labetalol
• Key quiz point: Spironolactone is currently NOT recommended during pregnancy (fetal antiandrogen effects), but this trial tests it POSTPARTUM as a novel mechanism

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SECTION 4 - BIOMARKER-GUIDED MANAGEMENT

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4A. PRERISK Study - sFlt-1/PlGF Calculator for PE Hospitalization (2025)

• Tool: PRERISK calculator = sFlt-1/PlGF ratio + gestational age + urinary protein:creatinine ratio; predicts PE-related complications
• Design: n=877 women (442 intervention, 435 control) with suspected/confirmed PE
• Intervention: Admission guided by PRERISK score (hospitalize if score ≥5%) vs routine care
• Results:
  • Complications: 41.6% (PRERISK-guided) vs 39.5% (control) - NOT non-inferior (aRR 1.06)
  • Hospitalization reduction: NOT achieved (23.6% vs 26.3% achieving low hospitalization ratio; p=0.34)
  • Per-protocol: PRERISK group had MORE complications (47.8% vs 41.7%, aRR 1.19)
• Conclusion: Routine sFlt-1/PlGF-based PRERISK score with 5% cutoff for hospitalization decisions is NOT recommended
• Key quiz point: Despite sFlt-1/PlGF being a valid PE predictor, this specific calculator did NOT safely reduce admissions - potentially missed patients who needed care

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4B. Reduced AT2R Signaling After Preeclampsia (Phase I, 2025)

• Women post-preeclampsia have >4x CVD risk vs uncomplicated pregnancy
• Finding: Reduced AT2R (angiotensin type 2 receptor) expression and AT2R-mediated vasodilation in women post-PE
• Acute AT2R activation with Compound 21 (AT2R agonist) improved endothelial function and NO-dependent dilation in post-PE women
• Key quiz point: AT2R signaling impairment contributes to persistent postpartum endothelial dysfunction; AT2R agonists are a potential future therapeutic target

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SECTION 5 - SUPPLEMENTATION TRIALS

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5A. Vitamin D for Preeclampsia Prevention - Meta-Analysis (2024)

• Vitamin D supplementation reduced preeclampsia risk by 44.8% (RR 0.55, 95% CI 0.43-0.71; p<0.0001)
• Reduced preterm labor by 30% (RR 0.70, 0.51-0.96; p=0.029)
• Raised serum 25(OH)D by mean 32.42 nmol/L
• No significant effect on low birth weight or Apgar scores
• Effect stronger when control group received placebo vs low-dose vitamin D
• Key quiz point: 44.8% reduction in PE risk with Vit D - significant but benefit on neonatal outcomes unclear

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5B. Calcium Supplementation for Preeclampsia - Challenging the Evidence (2024)

• Classic meta-analyses claimed calcium reduces PE risk by 55% (RR 0.45)
• Sensitivity analysis by study size: The 3 largest trials (88% of total n=15,730) showed RR = 0.92 (0.80-1.06) - NO significant effect
• Heterogeneity (I²) jumped from 0% to 70% when smaller studies were included
• Conclusion: The 55% reduction figure is driven by small, likely biased studies; the effect may be much smaller or absent
• Key quiz point: Be cautious - calcium for PE prevention may be less effective than guidelines suggest; small-study bias in pooled analyses

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5C. Polyphenols for Preeclampsia - Systematic Review (2025)

• 6 polyphenol candidates assessed: EGCG, resveratrol, Salvia miltiorrhiza, Bryophyllum pinnatum, raspberry/cranberry
• EGCG + nifedipine vs nifedipine alone: Reduced time to BP control (MD -14.1 min) and increased time to next hypertensive crisis (+3.1h) - but LOW certainty (1 trial, 349 women)
• Resveratrol + nifedipine: Similar benefit pattern (MD -15.5 min to BP control) - LOW certainty
• No differences for other agents or clinical endpoints
• Key quiz point: Polyphenols (EGCG, resveratrol) show signal as adjuncts to nifedipine but evidence is LOW certainty; not ready for clinical use

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SECTION 6 - LIFESTYLE AND BEHAVIORAL INTERVENTIONS

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6A. App-Based Physical Activity in Women with Prior HDP (2025)

• n=619 women with prior hypertensive pregnancy disorder
• Three-arm RCT: control vs motivation app vs action app (8 weeks)
• No significant treatment effect on MVPA (moderate-to-vigorous physical activity) for either intervention
• Possible explanations: high baseline activity in controls; need to target "automatic" behavior processes
• Key quiz point: App-based physical activity interventions for secondary cardiovascular prevention post-HDP do NOT improve exercise levels vs standard care in this design

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SECTION 7 - LONG-TERM CARDIOVASCULAR CONSEQUENCES

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7A. Atherosclerosis After Preeclampsia - Meta-Analysis (2026)

• Women with prior PE: pooled OR for atherosclerotic plaque = 1.57 (95% CI 1.39-1.78)
• Age-stratified risk:
  • 30-39 years: OR 0.64 (NOT significant)
  • 40-49 years: OR 1.59 (SIGNIFICANT)
  • 50-60 years: OR 2.00 (SIGNIFICANT)
• Key finding: Women with previous PE develop atherosclerosis approximately 10 years earlier than women with uncomplicated pregnancies
• Key quiz point: Pre-eclampsia accelerates atherosclerosis by ~10 years; surveillance should begin actively at age 40, not 50

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7B. Post-HDP Preventive Care Utilization - ACOG 2026

• Only 35.3% of insured women with HDP had a preventive care visit within 12 months postpartum
• Despite known cardiovascular risk, postpartum follow-up is critically underutilized
• Key quiz point: Preventive care uptake after HDP is poor, even in insured populations

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QUICK REFERENCE TABLE FOR QUIZZES

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KEY ONGOING TRIAL TO WATCH

• Phase 2 | MGH + BWH + UPMC | Currently recruiting
• Population: Women with HDP (gestational HTN or PE) + pre-pregnancy overweight/obesity
• Intervention: Spironolactone 25 mg/day x 12 weeks postpartum vs placebo
• Primary outcome: BP and cardiovascular health at 9 months postpartum
• Novel mechanism: Aldosterone antagonism

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