User login
Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.
“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.
To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.
The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.
Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).
During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.
On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).
Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.
From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).
The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.
Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.
The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.
SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.
Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.
“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.
To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.
The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.
Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).
During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.
On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).
Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.
From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).
The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.
Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.
The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.
SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.
Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.
“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.
To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.
The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.
Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).
During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.
On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).
Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.
From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).
The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.
Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.
The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.
SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM