Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 Trial

J Clin Endocrinol Metab. 2020 Nov 1;105(11):3384-3395. doi: 10.1210/clinem/dgaa450.


Context: Abaloparatide is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture.

Objectives: We assessed the cardiovascular safety profile of abaloparatide.

Design: Review of heart rate (HR), blood pressure (BP), and cardiovascular-related adverse events (AEs), including major adverse cardiovascular events (MACEs) and heart failure (HF) from: (a) ACTIVE (NCT01343004), a phase 3 trial that randomized 2463 postmenopausal women with osteoporosis to abaloparatide, teriparatide, or placebo for 18 months; (b) ACTIVExtend (NCT01657162), where participants from the abaloparatide and placebo arms received alendronate for 2 years; and (c) a pharmacology study in 55 healthy adults.

Results: Abaloparatide and teriparatide transiently increased HR relative to placebo. Following first dose, mean (standard deviation [SD]) HR change from pretreatment to 1 hour posttreatment was 7.9 (8.5) beats per minute (bpm) for abaloparatide, 5.3 (7.5) for teriparatide, and 1.2 (7.1) for placebo. A similar pattern was observed over subsequent visits. In healthy volunteers, HR increase resolved within 4 hours. The corresponding change in mean supine systolic and diastolic BP 1 hour posttreatment was -2.7/-3.6 mmHg (abaloparatide), -2.0/-3.6 (teriparatide), and -1.5/-2.3 (placebo). The percentage of participants with serious cardiac AEs was similar among groups (0.9%-1.0%). In a post hoc analysis, time to first incidence of MACE + HF was longer with abaloparatide (P = 0.02 vs placebo) and teriparatide (P = 0.04 vs placebo).

Conclusions: Abaloparatide was associated with transient increases in HR and small decreases in BP in postmenopausal women with osteoporosis, with no increase in risk of serious cardiac AEs, MACE, or HF.

Keywords: MACE; abaloparatide; blood pressure; cardiovascular; heart rate; osteoporosis.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Pressure / drug effects*
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / therapeutic use
  • Female
  • Heart Failure / chemically induced*
  • Heart Rate / drug effects*
  • Humans
  • Middle Aged
  • Osteoporosis / drug therapy*
  • Parathyroid Hormone-Related Protein / administration & dosage
  • Parathyroid Hormone-Related Protein / adverse effects*
  • Parathyroid Hormone-Related Protein / therapeutic use
  • Postmenopause
  • Teriparatide / administration & dosage
  • Teriparatide / adverse effects
  • Teriparatide / therapeutic use
  • Treatment Outcome


  • Bone Density Conservation Agents
  • Parathyroid Hormone-Related Protein
  • Teriparatide
  • abaloparatide

Associated data