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Thadani et al found a decreased amplitude and duration of the antianginal response to ISDN after 2 weeks of 4 times daily therapy, even though the last dose was taken at 8 pm and the first dose was taken at 8 am. In clinical practice, patients are up-titrated; failure to do so during a study of a nitrate administered long term is likely to lead to erroneous conclusions. Long-term Effectiveness Our findings relate only indirectly to the question of patch effectiveness during long-term use. Our results would obviously have been more relevant had our subjects been using patches, rather than ISDN, for the several weeks prior to the definitive trial. The patch study, however, was only one arm of a multiarm study, and overall considerations dictated the protocol we employed. Our protocol, by testing patients already taking ISDN 3 times daily, might be considered to have tested the patches in a situation akin to that of patients who had been using the patches long term during a 12-hour daytime period. In fact, five of the eight patients completing our study used the same doses long term. Single-blind testing with real and placebo patches, with and without an overnight patch-off interval, indicated that even after two to three months of continuous patch application, considerable antianginal effectiveness remained in this small, select group.