*While guidelines surrounding erythrocytosis have thus far involved an absolute upper limit cutoff for safety, studies have not investigated whether the magnitude of change in Hct while on TTh is a risk for MACE.
*We separated Hct into 5 separate quintiles and investigated how risks of MACE changed as Hct increased through these ranges while on TTh compared to men who did not experience an increase. We found that increases in Hct conferred an subsequent risk of MACE, regardless of the final upper limit. The risk of MACE was highest in those men who underwent the largest increases in Hct.
*This study has several important implications. Until recently, studies that have informed FDA warnings, or those that have showed TTh to be safe with respect to MACE have not looked at an underlying cause for the association. Recently, Hct over 52% has been found to be an important intermediary linking TTh and MACE.9 This study looked at a simple cutoff of 52%, and so did not provide any information on whether a large increase in Hct, while still remaining under 52%, was important. Our study suggests that all men, regardless of initial Hct, can potentially be at risk for MACE if their Hct increases. Men can have a Hct below guideline based cutoffs, but if the overall increase is large enough despite not reaching the upper limit of cutoff for changing dose or therapeutic phlebotomy, they may still experience risk for an adverse event. This may mean more careful tracking of Hct while on TTh instead of simply looking for an upper limit during the first 2 years of therapy.
