The likelihood of people dying because their medication has a side effect that affects the electrical activity of the heart is being reduced - thanks to a better understanding of why this happens and the development of tests to predict it.
The progress made on this topic was discussed by leading scientists at The Federation of European Pharmacological Societies (EPHAR) 2008 Congress in Manchester on Monday, 14 July, 2008.
Many kinds of medicine are associated with this adverse drug reaction, which initially involves a slowing of the electrical recovery of the heart each time it beats - known as QT prolongation.
Although this effect is not in itself dangerous, in a small percentage of people, particularly those with existing heart problems, it may lead to a potentially fatal abnormal heart rhythm known as Torsades de Pointes (TdP).
The symposium at the University of Manchester reviewed how tests done before potential new medicines are given to patients can be used to assess the probability that a drug will lead to QT prolongation or to the actual risk (TdP).
Leading European researchers met at the conference, which was hosted by the British Pharmacological Society, to discuss what early testing is done, how the results are used, how good they are at predicting effects on electrical activity in the human heart and what areas there may be for improvement.
Symposium organizer Dr Jean-Pierre Valentin of AstraZeneca R&D, Alderley Park, Cheshire, says that although significant progress has been made, which has decreased the number of old and new drugs carrying this cardiac safety risk, there is still more work to be done before strategies for assessing the risk are optimal.
He said: "The work being discussed is just one element of a discipline known as safety pharmacology. This involves determining which drug side effects could potentially be life-threatening and then trying to put in place tests that predict whether a given chemical might have one of these serious side effects in humans.
"By law, these tests must be done before a potential drug is first given to humans. In this way, the ultimate aim is to discover new medicines that can be developed rapidly and safely without causing any side-effects.
Dr Valentin continued: "Because the biology of the human body is so complex, no single group has the resources or breadth of knowledge to devise the best possible approach to predicting and preventing a given side effect. Rapid progress therefore needs academic and pharmaceutical company pharmacologists, doctors, government agencies and patients to collaborate as much as possible in order to share their knowledge and data. The symposium is just one mechanism for trying to achieve this.
Speaking specifically about TdP he said: "Until recently, the first indication that a drug carried a TdP risk was in patients, and, since it is a rare side-effect, this was only after millions patients had taken the drug.
"Although the low incidence of TdP might suggest relatively little need for concern, some of the medicines causing TdP were only for minor treatments such as hay fever, in which case the safety risk of the drug far outweighed the benefit to the patient.
"Medicines for non life-threatening diseases that are known to cause TdP in man are no longer available, but for serious conditions, such as cancer, the risk of TdP is far lower than the risk of dying from cancer so the use of such drugs in still justified but requires very careful, additional monitoring by doctors.
"Therefore, the challenge is to be able to produce medicines for all health issues, irrespective of their severity, that carry no TdP risk. This is particularly important because of the large number of people with cardiovascular diseases that would increase their TdP risk - such as those with high blood pressure, high cholesterol and diabetes.
"The most important advance in understanding this side-effect was the realisation, based on the work of many scientists, that the fundamental cause is most likely to be the drug sticking to a particular protein in the heart.