Bromocriptine quick release (BCQR) improves blood pressure and central and peripheral aortic stiffness and pressure hemodynamics in adolescents with type 1 diabetes (T1D), a placebo-controlled crossover trial has found.
“We know that abnormalities in the large vessels around the heart ― the aorta and its primary branches ― begin to develop in early childhood in people with type 1 diabetes,” first author Michal Schäfer, PhD, University of Colorado School of Medicine in Aurora, said in a statement.
“We found that bromocriptine has the potential to slow down the development of those abnormalities and decrease the risk for cardiovascular disease in this population,” Schäfer added.
A once-daily BCQR formulation was recently developed to enhance central nervous system dopaminergic activity. It has been approved to treat adults with type 2 diabetes after having been shown to reduce the incidence of major adverse cardiovascular events after 1 year of treatment.
However, in T1D, the therapeutic efficacy of BCQR and its effects on the heart were unstudied.
“Many studies have shown benefits of BCQR in patients with type 2 diabetes as an adjunct to standard medications. This was the first study to investigate BCQR in children and adolescents with T1D,” Schäfer told theheart.org | Medscape Cardiology.
The BCQR-T1D study tested the cardiovascular and metabolic impact of BCQR (Cycloset) in 34 adolescents (mean age, 15 years; A1c = 8.6) with T1D for a median duration of 6 years.
Participants were randomly allocated (1:1) to receive BCQR or matching placebo for 4 weeks and were then crossed over to the alternate treatment for 4 weeks after a 4-week washout period.
In each phase, the medication was titrated as follows: BCQR 0.8 mg or placebo one pill every morning for 1 week, then two pills every morning for 1 week, and finally four pills every morning for the remainder of the 4 weeks.
Compared with placebo, BCQR decreased systolic blood pressure (mean difference, 5 mm Hg; 95% CI, 3 – 7; P < .001) and diastolic blood pressure (mean difference, 2 mm Hg; 95% CI, 4 – 0; P = .039) at the end of 4 weeks.
Aortic stiffness was also reduced with BCQR therapy. Improvement in aortic stiffness was greatest in the ascending aorta, with reduced pulse-wave velocity (mean change, 0.4 m/s; P = .018) and an increase in distensibility (mean change, 0.08% per mm Hg; P = .017).
In the thoracoabdominal aorta, BCQR therapy was also associated with reduced pulse-wave velocity (mean change, 0.2 m/s; P = .007) and increased distensibility (mean change, 0.05% per mm Hg; P = .013), compared with placebo.
“Given that our study had positive results by showing that BCQR can improve blood pressure and normalize aortic stiffness in a short period of time, we hope that BCQR might help mitigate cardiovascular disease in patients with T1D,” Schäfer told theheart.org | Medscape Cardiology.
“Our results need to be validated in a larger prospective study and ideally using a randomized controlled trial prior to broader clinical application. We hope that our results will stimulate these efforts and provide further insights into adverse effects of type 1 diabetes on cardiovascular health,” Schäfer added.
Jordana Cohen, MD, with the University of Pennsylvania Perelman School of Medicine, Philadelphia, who wasn’t involved in the study, noted that it’s the first study to evaluate the effect of BCQR in T1D and in a pediatric population on several measures of large and medium artery stiffness.
“This is an important intermediate measure of vascular damage in diabetes. It is a novel and important investigation,” Cohen told theheart.org | Medscape Cardiology.
“Hard outcomes (like major adverse cardiac events) are very difficult to assess for in young patients because they take a very long period of time to develop, so I think mechanistic studies like this are very important to guide management and risk attenuation,” Cohen added.
“These data are quite compelling, but the study is very small and short-lived. I would be interested in seeing the replicability of these findings and the safety of the medication in this population over a longer period of follow-up before recommending it for widespread use,” Cohen added.
Support for the study was provided by the National Institutes of Health and by a grant from JDRF. Schafer and Cohen have disclosed no relevant financial relationships.
Hypertension. Published online December 6, 2022. Abstract