Drug Induced Arrhythmia Risk Evaluation (DARE) Study
The DSRU is collaborating with cardiologists and geneticists at St George’s,
What is Pro-arrhythmia and why is the DARE study important?
Sudden death and serious disturbances of heart rhythm are important and not highly publicised adverse effects of many drugs. Some of the causative drugs are established drugs which have been widely used for many years. These effects which sometimes occur in young patients can be devastating.
DARE is an Example of a Pharmacogenetic Study
There has been immense scientific progress in the last few years in the understanding of the biological basis and possible genetic predisposition for developing these reactions (i.e. the study of drug effects on genetically inherited differences) known as pharmacogenetics. Large studies based on large numbers of patients are needed to better understand the relationships between sudden death / serious cardiac rhythm disturbances and cellular and genetic predispositions in patients who suffered the reactions. The DARE study aims to build up a database or registry of such patients to systematically document and follow up incident cases in England, comparing them with control patients (with no abnormalities) and analyse blood samples from cases and controls to look for possible genetic differences.
The Future
The long term goal of pharmacogenetic studies such as DARE means that individual patient therapy might in the future be tailored to the genetic profile of that individual and therefore avoidance of serious side effects such as drug-induced arrhythmia may become possible. Thus the theoretical possibility of state of the art “personalised medicines” may become closer to reality. The collaboration between the DSRU and the team at St George’s that has now been established will enable the methodology, infrastructure and more importantly a ready-made team to be utilised for future studies. We will seek to undertake additional nationwide epidemiological studies of other such rare adverse events with the possibility of building up further unique databases and registries of rare adverse drug events.
Study Update
The initial DARE study cohort is now complete with 112 cases and 312 controls. Both epidemiological and genetic analysis is underway.
Oral Abstracts (Cohort Description and Preliminary Results of the Drug-Induced Arrhythmia Risk Evaluation (DARE) Study. V Marshall and Common variants in the NOS1AP (CAPON) gene are associated with amiodarone-induced ventricular arrhythmias: early results from the DARE study. E Behr) were presented at the HRUK Conference in Birmingham in October 2009
The DARE team, however, still wants to add to the cohort of Drug-induced ventricular arrhythmia and active recruitment is ongoing through two collaborative ventures:
· The DARE Network has entered a collaborative arrangement with the SAEC (International Serious Adverse Event Consortium Ltd) to identify DNA variants that are clinically useful in understanding and predicting the risk of drug-induced serious adverse events, including Drug-Induced Arrhythmia.
· A proposal entitled: "Arrhythmogenic potential of drugs", (ARITMO) submitted by a consortium of 17 European centres (including UK, Netherlands, Sweden, France, Italy and Spain), to the European Commission as an FP7 application, including the DARE network, has been favourably evaluated by the Commission services with the help of independent experts and was launched in February 2010.
For further information please contact: Pauline Telfer, Study Administrator 02380 408615 pauline.telfer@dsru.org or Dr Vanessa Marshall, Study Manager 02380 408603 vanessa.marshall@dsru.org
For referral of new cases please contact: Linda Robinson, DARE Study Research Nurse 01902 701535 or 07971 646395 linda.robinson@dsru.org
Hospital Physician Information Sheet DARE Study Flyer