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

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.

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

© Endocrine Society 2020.

Figures

Figure 1.

Baseline heart rate by treatment group in ACTIVE. bpm, beats per minute.

Figure 2.

Distribution of maximum heart rate in ACTIVE. A) 1 hour postdose by treatment group. B) Change from pre- to postdose. bpm, beats per minute.

Figure 3.

Overlap of distribution of maximum 1-hour postdose heart rate for abaloparatide and teriparatide in ACTIVE. bpm, beats per minute.

Figure 4.

Heart rate change over 24 hours following a single administration of abaloparatide versus placebo in healthy participants (90% CI). 5 bpm equals expected variability of resting heart rate in healthy participants. bpm, beats per minute; CI, confidence interval.

Figure 5.

Time to first incidence of MACE and MACE + HF in ACTIVE and ACTIVExtend. A) ACTIVE and ACTIVExtend MACE; B) ACTIVE and ACTIVExtend MACE + HF. ABL, abaloparatide; ALN, alendronate; HF, heart failure; MACE, major adverse cardiovascular event; mo, months; PBO, placebo; TPTD, teriparatide.