Genetic clues for responders to heart failure drug identified

Oct 18 2012

By Piriya Mahendra, medwireNews Reporter

Researchers have identified genetic signatures that predict which patients respond to the beta blocker bucindolol.

Stephen Liggett (University of South Florida, USA) and team found that the combination of the β₁ adrenergic receptor [AR] Arg389 Gly and α_2c AR Ins (wild type [Wt]) 322-325 deletion [Del] polymorphisms influenced bucindolol efficacy consistent with their pharmacologic interactions.

The team also found that these polymorphisms combined identified subpopulations for whom bucindolol had enhanced (β₁389 Arg homozygous), intermediate (β₁389 Gly carriers and α_2c 322-325 Wt homozygous), and no (β₁389 Gly carriers and α_2c 322-325 Del carriers) efficacy.

"We have been studying the molecular basis of heart failure (HF) in the laboratory with a goal of finding genetic variations in a patient's DNA that alter how drugs work," commented Liggett in a press statement.

"We took this knowledge from the lab to patients and found that we can indeed, using a two-gene test, identify individuals with HF who will not respond to bucindolol and those who have an especially favorable treatment response."

He added: "We also identified those who will have an intermediate level of response."

The research team believes the findings will have implications for clinical practice, as the genetic test could theoretically be used to target bucindolol to responders. Just as importantly, they say, the use of bucindolol could be avoided in patients who are predicted to not benefit from the drug according to the genetic test. These patients could then be spared potential side effects.

As reported in PLoS One, the study involved 1040 patients who participated in the Beta Blocker Evaluation of Survival Trial (BEST). The researchers analyzed mortality, hospital admissions for HF exacerbations, and other clinical outcome indicators of drug performance.

"The results showed that the choice of the best drug for a given patient, made the first time without a trial-and-error period, can be accomplished using this two-gene test," remarked Liggett.

He concluded: "In the not too distant future, such tests will become routine, and patient outcomes, and the efficiency and cost of medical care will be impacted in positive ways… If we can identify by straightforward tests which drug is best for which patient, drugs that work with certain smaller populations can be brought to the market, filling a somewhat empty pipeline of new drugs."

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