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

Context Abaloparatide is an FDA-approved PTHrp 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 (MACE) 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 (SD) HR change from pre-treatment to 1 hour post treatment was 7.9 (8.5) 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 post treatment 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 versus placebo) and teriparatide (P = 0.04 versus 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.