Suissa makes some criticisms on our paper and we would like to comment on them. He claims that our results are ‘unusual’ because they are consistent neither with two previous epidemiological studies nor with the analysis made by the WHO Collaborative Centre based on spontaneous reports. His interpretation is puzzling as he omitted to mention in his letter that the estimates for individual antihistimanics were based on very small number of cases, and consequently all estimates of relative risk were overlapping. We commented extensively on these three papers in our manuscript, and concluded that our findings were consistent with their results and others, despite important methological differences and supported the hypothesis that the risk of ventricular arrhythmia associated with terfenadine in the population at large was not materially different from the one presented with other antihistamines as a group.
Suissa raised some interested methological issues. Following his suggestions we have re-examined our data searching for any evidence supporting the various potential biases he postulated. First, ‘depletion of susceptibles’ may certainly be a theoretical source of bias when only first events are considered; however, in our study, all nine cases with a ventricular arrhythmia episode during current use of antihistamines did not present any other new episode after the first one during an average follow-up of 4 years after the index episode, irrespective of exposure status. Second, Suissa argues that the increased risk observed with non-sedating antihistamines other than terfenadine can be explained if patients at higher risk of ventricular arrhythmia have been switched from terfenadine to these other antihistamines; nevertheless, our data indicate that none of the six cases who were current users of other non-sedating antihistamines were past users of terfenadine. Finally, Suissa contends that the decreasing use of non-sedating antihistamines over the study period may have increased the rate of ventricular arrhythmia among non-users, as an increasing number of them may have actually become users of OTC antihistamines; again this speculation is not consistent with our data: the rate of ventricular arrhythmia among non-users was one per 17 000 person-years over the period 1992–93 and one per 28 000 person-years over the period 1994–96, a trend in the opposite direction predicted by Suissa.
In conclusion, we were not able to substantiate empirically any of the limitations pointed out by Suissa, which, we assume, reinforces the validity of our results.