Highlow study - Highlow study

Nov 21, 2022
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.
Date Published:
10/28/2022
Date Updated:
11/21/2022
Original Posted Date:
11/21/2022
References

Contribution To Literature:

The Highlow study failed to show that weight-adjusted intermediate-dose LMWH improved outcomes among pregnant women with a history of venous thromboembolism.

Description:

The goal of the trial was to evaluate weight-adjusted intermediate-dose low molecular weight heparin (LMWH) compared with fixed low-dose LMWH among pregnant women with a history of venous thromboembolism.

Study Design

  • Randomized
  • Parallel
  • Open-label
  • Stratified

Pregnant women with a history of venous thromboembolism were randomized to weight-adjusted intermediate-dose LMWH (n = 555) vs. fixed low-dose LMWH (n = 555) until 6 weeks post-partum.

The type of LMWH varied according to local practice. In the weight-adjusted intermediate-dose group, the dose was approximately one-half of the therapeutic dose. Study medication was administered subcutaneously once daily.

  • Total number of enrollees: 1,110
  • Duration of follow-up: median 247 days
  • Mean patient age: 32 years
  • Percentage female: 100%

Inclusion criteria:

  • Pregnant women ≥18 years of age
  • History of venous thromboembolism
  • Gestational age ≤14 weeks

Exclusion criteria:

  • Venous thromboembolism related to surgery, major trauma, or plaster cast immobilization
  • Indication for therapeutic-dose anticoagulant
  • Contraindication to LMWH

Other salient features/characteristics:

  • Provoking factor for venous thromboembolism: hormone therapy for contraception in 58%

Principal Findings:

The primary efficacy outcome, venous thromboembolism (deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), occurred in 2% of the weight-adjusted intermediate-dose LMWH group vs. 3% of the fixed low-dose LMWH group (p = 0.33).

The primary safety outcome, major bleeding (antepartum, early post-partum, and late post-partum major bleeding) until 6 weeks post-partum, occurred in 4% of the weight-adjusted intermediate-dose LMWH group vs. 4% of the fixed low-dose LMWH group (p = not significant).

Interpretation:

Among pregnant women with a history of venous thromboembolism, weight-adjusted intermediate-dose LMWH was not superior to fixed low-dose LMWH. Weight-adjusted intermediate-dose LMWH was not associated with a reduction in recurrent venous thromboembolism. Low-dose LMWH for thromboprophylaxis during pregnancy is preferred.

References:

Bistervels IM, Buchmüller A, Wiegers HM, et al., on behalf of the Highlow Block writing committee and Highlow Investigators. Intermediate dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicenter, randomized, controlled trial. Lancet 2022;400:1777-87.

Editorial Comment: Roeters van Lennep JE, Nerenberg KA. Delivering evidence to prevent recurrent venous thromboembolism in pregnancy. Lancet 2022;400:1743-5.

Clinical Topics: Anticoagulation Management, Congenital Heart Disease and Pediatric Cardiology, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention

Keywords: Anticoagulants, Contraception, Gestational Age, Hemorrhage, Hormonal Contraception, Heparin, Low-Molecular-Weight, Hormones, Infant, Postpartum Period, Pregnancy, Pregnant Women, Pulmonary Embolism, Primary Prevention, Secondary Prevention, Venous Thromboembolism, Venous Thrombosis, Vascular Diseases


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