PMID- 32658264
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20210216
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 105
IP  - 11
DP  - 2020 Nov 1
TI  - Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: 
      Analysis From the ACTIVE Phase 3 Trial.
PG  - 3384-95
LID - dgaa450 [pii]
LID - 10.1210/clinem/dgaa450 [doi]
AB  - 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.
CI  - (c) Endocrine Society 2020.
FAU - Cosman, Felicia
AU  - Cosman F
AD  - Department of Medicine, Columbia University, New York, New York.
FAU - Peterson, Linda R
AU  - Peterson LR
AD  - Diabetic Cardiovascular Disease Center and Department of Medicine, Washington 
      University, St Louis, Missouri.
FAU - Towler, Dwight A
AU  - Towler DA
AD  - Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
FAU - Mitlak, Bruce
AU  - Mitlak B
AD  - Clinical Development, Radius Health, Inc., Waltham, Massachusetts.
FAU - Wang, Yamei
AU  - Wang Y
AD  - Biostatistics, Radius Health, Inc., Waltham, Massachusetts.
FAU - Cummings, Steven R
AU  - Cummings SR
AD  - San Francisco Coordinating Center, Sutter Health, California; University of 
      California, San Francisco, California.
LA  - eng
SI  - ClinicalTrials.gov/NCT01343004
SI  - ClinicalTrials.gov/NCT01657162
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Parathyroid Hormone-Related Protein)
RN  - 10T9CSU89I (Teriparatide)
RN  - AVK0I6HY2U (abaloparatide)
SB  - IM
MH  - Aged
MH  - Blood Pressure/*drug effects
MH  - Bone Density/*drug effects
MH  - Bone Density Conservation Agents/administration & dosage/*adverse 
      effects/therapeutic use
MH  - Female
MH  - Heart Failure/*chemically induced
MH  - Heart Rate/*drug effects
MH  - Humans
MH  - Middle Aged
MH  - Osteoporosis/*drug therapy
MH  - Parathyroid Hormone-Related Protein/administration & dosage/*adverse 
      effects/therapeutic use
MH  - Postmenopause
MH  - Teriparatide/administration & dosage/adverse effects/therapeutic use
MH  - Treatment Outcome
PMC - PMC7500469
OTO - NOTNLM
OT  - MACE
OT  - abaloparatide
OT  - blood pressure
OT  - cardiovascular
OT  - heart rate
OT  - osteoporosis
EDAT- 2020/07/14 06:00
MHDA- 2021/02/17 06:00
PMCR- 2020/07/13
CRDT- 2020/07/14 06:00
PHST- 2020/04/22 00:00 [received]
PHST- 2020/07/08 00:00 [accepted]
PHST- 2020/07/14 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/07/14 06:00 [entrez]
PHST- 2020/07/13 00:00 [pmc-release]
AID - 5870711 [pii]
AID - dgaa450 [pii]
AID - 10.1210/clinem/dgaa450 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2020 Nov 1;105(11):3384-95. doi: 10.1210/clinem/dgaa450.