(p. 182) Anti-arrhythmic drug therapy 

The definition of a ‘landmark paper’ is multi-factorial as a paper can only be measured ultimately by its impact on clinical practice, whether positively, that is, by demonstrating the application of a specific therapy which has a significant and sustained clinical effect, or negatively, by informing the physician that therapy is not efficacious, or even dangerous. The technical criteria for such a publication should include the fact that the trial of therapy was randomized and double-blinded to avoid bias and the end points assessed should be unequivocal. The population recruited into the trial should reflect the target population treated by the physician such that it is relevant to contemporary practice. Therefore, any evaluation of landmark clinical trials of anti-arrhythmic drug therapy should begin with high quality randomized placebo controlled trials in large populations looking at key unequivocal primary end points which impact both on the individual patient and the management of populations in terms of mortality and cost-efficacy. In the anti-arrhythmic therapy field there are numerous small studies which demonstrate efficacy, but frequently the groups studied are too small to allow application to the wider population. The effects of these agents are often not pure or achieved through a single target. Figure 11.1 summarizes the main anti-arrhythmic classes, modulators of arrhythmia, and key therapeutic targets based upon arrhythmia mechanisms.

In this series of ten papers we have aimed to highlight the studies that have significantly changed or informed practice with the highest level of evidence. The series can be divided into trials of agents to prevent lethal arrhythmia and sudden death, atrial anti-arrhythmic agents (reflecting the high burden of atrial fibrillation (AF) in the community), and those trials which were important negatives, showing the detrimental effects of certain agents in specific patient populations.