Genotypes Forecast Response to Bucindolol Treatment for Heart Failure: Presented at HFSA

To print: Select File and then Print from your browser's menu
---------------------------------------------------------------------------------------
Title: Genotypes Forecast Response to Bucindolol Treatment for Heart Failure: Presented at HFSA
URL: http://www.pslgroup.com/dg/22D3D2.htm
Doctor's Guide
September 22, 2008

By Jill Stein

TORONTO -- September 22, 2008 -- The therapeutic effects of bucindolol can be optimised by pharmacogenetic targeting of polymorphisms in the beta1 and alpha2c adrenergic receptors, according to a study presented here at the Heart Failure Society of America (HFSA) 12th Annual Scientific Meeting.

The study also showed that heart failure patients who exhibit beta1 389 Arg/Arg with the alpha2c 322-325 wild-type or deletion genotype combination who are treated with bucindolol have a lower rate of hospitalisation and death, according to the poster presented on September 22.

Christopher O'Connor, MD, Duke Heart Failure Program and Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, and colleagues conducted a substudy of 1,040 patients enrolled in the Beta-Blocker Evaluation of Survival Trial (BEST) , purportedly the largest heart failure mortality trial to date.

The investigators assessed the response to bucindolol treatment in patients with polymorphisms in 2 adrenergic receptors that help regulate cardiac function: beta1 389 Arg/Gly and alpha2c 322-325 wild type/deletion.

Three distinct genotypes were detected that predicted a very favourable effect of bucindolol in 47% of patients, a favourable effect in 40%, and an unfavourable effect in 13% of patients.

Results showed that the beta1 389 Arg/Arg plus alpha2c 322-325 wild-type or deletion genotype combination was associated with 38% reduction in all-cause mortality (P < .05), 48% reduction in cardiovascular mortality (P < .05), 44% reduction in heart failure hospitalisations (P < .01), and 36% reduction in cardiovascular hospitalisations (P < .01).

The study also found that the beta1 389 Gly carrier plus alpha2c 322-325 wild-type genotype combination was associated with greater bucindolol efficacy for the cardiovascular endpoint only.

Bucindolol treatment was not associated with improved clinical outcomes in patients with the beta1 389 Gly carrier and alpha2c 322-325 deletion genotype.

It is possible that factors other than the combined genotype not accounted for by the adjusted analysis could have influenced the outcome, Dr. O'Connor and colleagues wrote in the poster.

Overall, the results show that the beta1 389 Arg/Gly and alpha2c 322-325 wild-type or deletion polymorphisms influenced the effects of bucindolol treatment on hospitalisations and death in the BEST study.

Patients with the beta1 389 Arg/Arg plus alpha2c 322-325 wild-type or deletion genotype combination had the greatest clinical response to bucindolol and represent a very favourable subgroup, he added.

Funding for this study was provided by ARCA biopharma, which has submitted a New Drug Application for bucindolol to the US Food and Drug Administration for the treatment of heart failure.

[Presentation title: Additive Effects of Beta1 389 Arg/Gly and Alpha 2c 322-325 Wild-Type/Del Genotype Combinations on Adjudicated Hospitalizations and Death in the Beta Blocker Evaluation of Survival Trial (BEST). Abstract 216]

http://www.docguide.com

Return to News Story Page

webmaster@pslgroup.com