Cardiovascular Safety of Abaloparatide in Postmenopausal Women with Osteoporosis: Analysis from the ACTIVE Phase 3 Trial

Felicia Cosman, Linda R. Peterson, Dwight A. Towler, Bruce Mitlak, Yamei Wang, Steven R. Cummings

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3384-3395
Number of pages12
JournalJournal of Clinical Endocrinology and Metabolism
Volume105
Issue number11
DOIs
StatePublished - Nov 1 2020

Keywords

  • Abaloparatide
  • Blood pressure
  • Cardiovascular
  • Heart rate
  • MACE
  • Osteoporosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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