Reply: Effects of Nitroglycerin Ointment on Mastectomy Flap Necrosis in Immediate Breast Reconstruction: A Randomized Controlled Trial

Sir: We thank Dr. Hwang for his interest in our article1 on the effects of nitroglycerin ointment on mastectomy flap necrosis. We would like to address his questions regarding dosing considerations of the nitroglycerin ointment and odds ratio reporting for this trial. There are a number of summary measures that can be used when reporting a between-group comparison of a binary outcome from a randomized trial; the absolute risk reduction (also called the risk difference), the relative risk reduction, and the odds ratio are the most common. We chose to present the risk difference because of its ease of interpretation. The odds ratio has useful mathematical properties but is the least intuitive and is often misinterpreted as a relative risk.2,3 When the outcome is not rare, the odds ratio will overestimate the relative risk. For example, in our study, the relative risk of mastectomy flap necrosis is 0.45 and the odds ratio is 0.35. Relative risks are easy to interpret but can exaggerate small, unimportant differences; for example, both a reduction from 30 percent to 15 percent and a reduction from 0.3 percent to 0.15 percent yield a relative risk of 0.5. However, this same property makes the relative risk attractive for meta-analysis when there is variation in the control group event rates.4 In our view, what is most important is to report the number of events in each group; readers can then calculate the summary measure of their choice as Dr. Hwang has done. We note that there is an error in Dr. Hwang’s letter; the p value is 0.006, not 0.068. Dr. Hwang also raises an interesting issue relating to the dosing of nitroglycerin ointment. We selected a dose of 45 mg to be applied as a thin layer concentrically from the center of the breast to the periphery. In reality, the ointment should be applied to areas of skin that are at highest risk of mastectomy flap necrosis. Often, the area most at risk is the nipple-areola complex, as it is the farthest point from the chest wall and relies on blood supply from the surrounding skin. We concede that this is not an exact science in that nitroglycerin ointment was not originally intended for its effect on vasodilation of the skin. Administration of nitroglycerin for cardiac patients is equally imprecise, as application surface areas vary and dosage is guided by the systemic response.5 Although the concept of a dose per unit area would be more scientific, we do not feel that it would be of any clinical benefit, as the dose that each patient could tolerate depends on many other factors, including body weight, blood pressure, and sensitivity to nitrates. Thus, clinical endpoints must guide the use of this ointment. As stated in our article, we recommend a single application of no more than 45 mg starting over the area of skin that is most at risk for necrosis. Blood pressure monitoring should be instituted routinely. We look forward to future studies exploring repeated application and dosing for bilateral cases. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. Perry Gdalevitch, M.D., M.Sc.Penelope Brasher, Ph.D.Sheina Macadam, M.D., M.S.Division of Plastic and Reconstructive SurgeryUniversity of British ColumbiaVancouver, British Columbia, Canada

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