Prolonged QTc interval is defined as a QTc longer than 440 ms (Reference KhanKhan, 2002); therefore, by this definition, the patient did not have a documented prolonged QTc interval prior to the introduction of rivastigmine.

As detailed in the original report of this case to Novartis, the patient had been admitted a number of weeks previously to a medical ward where he developed diarrhoea which was deemed responsible for the lowering of his potassium. As a result he received potassium supplements while the diarrhoea was ongoing and once the diarrhoea stopped the potassium was rechecked and the potassium supplements were discontinued. The patient had no diarrhoea at any stage during his treatment with rivastigmine that could have led to a further development of hypokalaemia. The patient had been receiving his other medications on a long-standing basis, including diltiazem for 5 years, and electrolytes checked intermittently had not shown previous problems with hypokalaemia. It is therefore unlikely that the patient was hypokalaemic at the time of the prolonged QTc interval.

The patient had no recent history of cardiac abnormalities apart from a myocardial infarct 6 years previously and long-standing hypertension. The patient had been on long-standing medication and there was no evidence of a prolonged QTc while on these medications. Although the patient had symptoms suggestive of dementia with Lewy bodies he did not fulfil the criteria for a diagnosis of probable dementia with Lewy bodies (Reference McKeith, Gelasko and KosakaMcKeith et al, 1996).

In conclusion, this patient had evidence of a normal QTc interval prior to the introduction of the rivastigmine and developed a prolonged QTc while on the treatment which reverted to normal on discontinuation of the drug. His concomitant medication had been long-standing, he had no recent history of cardiac abnormalities and his previous hypokalaemia secondary to diarrhoea had been corrected. Therefore, we suggest there is a possibility of a causal relationship between rivastigmine and prolonged QTc interval. Independently, Novartis have received two isolated reports of QT interval prolongation, which the company have attributed to confounding factors such as co-medication and electrolyte abnormalities as well as insufficient/discrepancies in documentation (J. Collins (Novartis), personal communication, 2001).

I agree with Dr Inglis that the cholinesterase inhibitors are an invaluable part of our limited armamentarium in managing people with dementia but as with any new treatment only when a large number of patients are treated, many of whom will be taking multiple medications, have different comorbidities and be subject to other conditions that were not represented in the original trial population, will adverse effects become manifest that were otherwise not recognised, appreciated or expected. It is important that clinicians monitor, document and report adverse events. Unfortunately, experience demonstrates that this is frequently lacking and can result in the delayed recognition of potentially serious side-effects and interactions.