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The Express Publication by Kloner et al. (1)on the interactions between nitrates and tadalafil should be of interest to all cardiologists and physicians seeing patients with acute chest pain.
However, I have several questions: 1) What is the duration of erectile dysfunction efficacy of tadalifil? The long half-life suggests that responsiveness to the drug may last 2 to 3 days; do we know whether the blood pressure and heart rate effects of nitrates with tadalafil on board are concordant with the duration of improvement in sexual function? 2) It is unclear whether there is a repeat run-in of 7 days for both placebo and tadalafil after the cross-over, that is, is the second-half dosing the same as the first part of the protocol? 3) Why is the recommendation made to withhold concomitant use of a nitrate and tadalafil for 48 h when all data robustly support no interaction at this time interval? 4) The half-life of sildenafil, the gold standard phosphodiesterase 5 (PDE5) inhibitor is not provided. This would be useful, including the best estimate of its duration of its action, as well as the time period during which there is a potentially hazardous interaction between this PD5 inhibitor and nitrates. 5) Is it possible that an acute dosing interaction (no previous exposure for several days) with nitrates with sildenafil or tadalafil might induce a different response to nitrates than after 5 to 6 consecutive half-lives of the PD5 inhibition? Thus, it may be that a form of tolerance to nitrate hemodynamic effects could develop within days in the vasculature, attenuating the decrease in blood pressure and increase in heart rate after an individual has been taking a PD5 inhibitor for a considerable amount of time, as in this experiment. The protocol design does not really mirror the way sildenafil and tadalafil are used in daily living. It would be useful to know if there are data that answer these questions.
- American College of Cardiology Foundation